Policies that include information from the Final Rule

Policy

The State University of New York at Stony Brook is committed to fostering a research environment that prioritizes the rights and welfare of individuals involved in research Guided by the principles of respect for persons, beneficence, and justice as outlined in the Belmont Report, the University ensures that all research activities comply with relevant federal, state, and local laws To uphold these standards, the University has implemented a comprehensive human research protections program (HRPP).

Mission

The mission of the HRPP is to:

 Safeguard and promote the health and welfare of human research subjects by ensuring that their rights, safety and well-being are protected;

 Provide timely and high quality education, review and monitoring of human research projects; and

 Facilitate excellence in human subject research

The HRPP includes mechanisms to:

 Establish a formal process to monitor, evaluate and continually improve the protection of human research subjects;

 Dedicate resources sufficient to do so;

 Exercise oversight of research protection;

 Educate investigators and research staff about their ethical responsibility to protect research subjects; and

 When appropriate, intervene in research and respond directly to concerns of research subjects.

Institutional Authority

The University HRPP functions under University Policy #P202R, titled “Research Involving Human Subjects,” which was last revised and approved in May 2009 This policy outlines the operating procedures that govern the conduct and review of all human research conducted under the university's auspices.

University.” The HRPP Policy and these Standard Operating Procedures (SoPs) are available to all University investigators and research staff and posted on the Office of Research

Ethical Principles

The University is committed to conducting research with the highest regard for the welfare of human subjects It upholds and adheres to the principles of The Belmont Report: Ethical

Principles and Guidelines for the Protection of Human Subjects in Research by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research

Respect for Persons, which is ensured by obtaining informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations

Beneficence, which is assured by ensuring that possible benefits are maximized and possible risks are minimized to all human subjects

Justice, the equitable selection of subjects

The University’s Human Research Protection Program (HRPP) collaborates with the research community to guarantee the ethical and fair treatment of all human subjects involved in research activities.

Definitions

Agent: all individuals performing institutionally designated activities or exercising institutionally delegated authority or responsibility

Committees on Research Involving Human Subjects (CORIHS): see Institutional Review Board

The Common Rule, formally known as the "Federal Policy for the Protection of Human Subjects," is adopted by various federal agencies to ensure ethical standards in research involving human participants While each agency codifies the Common Rule independently, the language remains consistent with the Department of Health and Human Services (DHHS) regulations outlined in 45 CFR 46 Subpart A This document will reference the Common Rule as per DHHS regulations.

A clinical trial, as defined by the Common Rule and NIH Policy, is a research study that prospectively assigns one or more human subjects to various interventions, including placebo or control groups, to assess the impact of these interventions on biomedical or behavioral health outcomes Additionally, FDA regulations refer to these studies as "clinical investigations."

Engagement: an institution is considered engaged in a research project when the involvement of their employees or agents in that project includes any of the following:

 Intervention for research purposes with any human subjects of the research by performing invasive or noninvasive procedures

 Intervention for research purposes with any human subject of the research by manipulating the environment

 Interaction for research purposes with any human subject of the research

 Obtaining the informed consent of human subjects for the research

For research purposes, acquiring identifiable private information or biological specimens from various sources is essential This process encompasses a wide range of activities, including but not limited to the collection of personal data and biological materials that can be linked to specific individuals.

 Observing or recording private behavior;

 Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens provided by another institution; and

 Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens already in the possession of the investigators

Under the Common Rule, a human subject is defined as a living individual from whom an investigator gathers information or biospecimens through direct interaction or intervention This includes obtaining, studying, analyzing, or generating identifiable private information or biospecimens This definition is outlined in 45 CFR 46.102(e)(1).

"Intervention" refers to both physical methods used to collect information or biospecimens, such as venipuncture, and alterations made to the subject or their environment for research purposes, as defined by [45 CFR 46.102(e)(2)].

“Interaction” means communication or interpersonal contact between investigator and subject [45 CFR 46.102(e)(3)]

"Private information" refers to data regarding an individual's behavior in situations where they have a reasonable expectation of privacy, meaning they do not anticipate being observed or recorded It also includes information shared by individuals for specific purposes, such as medical records, which they expect to remain confidential and not disclosed publicly.

“Identifiable private information” means private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information

[45 CFR 46.102(e)(5)] Note: This definition is within the Common Rule For a discussion of identifiability under HIPAA, please see Section 16

“Identifiable biospecimen” means a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen [45 CFR

Note: The terms “subject” and “participant” are used interchangeably in this document and have the same definition

A human subject in research governed by FDA regulations (21 CFR 50 and 56) refers to an individual who participates in a clinical investigation, either receiving the test article or serving as a control This participant can be a healthy individual or someone with a medical condition or disease.

In the context of medical devices, a human subject or participant encompasses any individual whose tissue specimen is utilized or tested with an investigational device, irrespective of whether the specimens can be identified.

Note: The terms “subject” and “participant” are used interchangeably in this document and have the same definition

Human Subjects Research: any activity that meets the definition of “research” and involves

“human subjects” as defined by either the Common Rule or Food and Drug Administration (FDA) regulations

The Institutional Official (IO) is the designated representative of the University responsible for the Human Research Protection Program (HRPP) This individual holds legal authority to represent the institution and is the official signatory for all Assurance documents, thereby assuming the institution’s obligations The IO serves as the primary contact for communications regarding human subjects research with the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA), and other federal regulatory agencies.

The Institutional Review Board (IRB) is a designated committee at the University responsible for reviewing and approving research involving human subjects Its main goal is to ensure the protection of the rights and welfare of these individuals Additionally, the IRB may undertake other review functions as deemed necessary.

Research, as defined by the Common Rule, refers to a systematic investigation aimed at developing or contributing to generalized knowledge through research development, testing, and evaluation However, certain activities are explicitly excluded from this definition of research.

Scholarly and journalistic activities, such as oral history, journalism, and legal research, involve the collection and use of information focused on specific individuals Additionally, public health surveillance activities, which include the collection and testing of data or biospecimens, are conducted or authorized by public health authorities These activities are essential for identifying, monitoring, and assessing public health signals, disease outbreaks, and important health conditions, as well as analyzing trends and risk factors associated with diseases and consumer product-related injuries.

On March 19, 2020, it is essential to ensure timely situational awareness and prioritize actions during events or crises that threaten public health, whether due to natural or man-made disasters Additionally, the collection and analysis of information, biospecimens, or records by criminal justice agencies must be conducted legally and specifically for criminal justice or investigative purposes Furthermore, authorized operational activities, as determined by each agency, are critical to supporting intelligence, homeland security, defense, and other national security missions.

A "systematic investigation" refers to a structured research activity that follows a prospective study plan and includes data collection and analysis, whether quantitative or qualitative, aimed at addressing a specific research question Investigations intended to generate or enhance "generalizable knowledge" are designed to derive broad conclusions, meaning the insights obtained can be applicable to populations beyond the specific group studied.

Research (synonymous with Clinical Investigation, Study - for activities under FDA jurisdiction): any experiment that involves a test article and one or more human subjects, and that either:

To comply with FDA regulations, any use of a drug outside of its approved medical practice must meet the requirements outlined in section 505(i) or 520(g) of the Federal Food, Drug, and Cosmetic Act This includes activities that assess the safety or effectiveness of a device as specified in 21 CFR 812.2(a) and the definition of a drug use under 21 CFR 312.3(b).

Regulatory Compliance

The Human Research Protection Program (HRPP) ensures adherence to federal regulations, state laws, and institutional policies, including tribal laws from American Indian or Alaska Native tribes At the University, all human subjects research is conducted in alignment with the Common Rule and the regulations outlined in 21 CFR 50 and 56.

Regulatory compliance for research funded by other federal agencies (e.g., Department of Defense, Department of Energy, Department of Education etc.) is addressed in the SOP

Supplement: Additional Federal Criteria, as well as the Worksheet: Additional Federal Criteria to be used by IRB staff and members to ensure compliance with these specific regulations

The University implements the International Conference on Harmonization (ICH) Good Clinical Practices (GCP) Guidelines, also known as ICH-GCP or E6, in research projects when mandated by a sponsor, ensuring their application aligns with FDA and DHHS regulations.

The actions of the University will also conform to all other applicable federal, state, and local laws and regulations.

Federalwide Assurance (FWA)

Federally funded human subjects research must be conducted at facilities with a Federalwide Assurance (FWA) approved by the DHHS Office for Human Research Protections (OHRP) An FWA ensures compliance with federal regulations for the protection of human subjects and designates the Institutional Review Boards (IRBs) responsible for overseeing the research Additionally, it outlines the ethical principles guiding the research and identifies the individuals accountable for its proper conduct.

The University holds an OHRP-approved Federalwide Assurance (FWA# 00000125) and offers support for an on-site Institutional Review Board (IRB) Additionally, the Human Research Protection Program (HRPP) frequently collaborates with Advarra for industry-initiated and funded protocols, as well as the Pediatric and Adult Central IRBs of the National Cancer Institute for specific cooperative oncology group protocols.

On March 19, 2020, the process for utilizing external Institutional Review Boards (IRBs) is outlined on the Office of Research Compliance website The five designated IRBs are responsible for reviewing all human research protocols conducted under the University’s auspices, unless a reliance agreement is established to transfer IRB review to an external entity, as detailed in section 1.14 for multi-center research, including the SMART IRB Reliance Initiative (www.smartirb.org).

When human subjects research falls outside the Common Rule or FDA regulations, SBU ensures that participants receive comparable protections by implementing Common Rule standards, while allowing for intentional deviations that do not significantly reduce these protections, as outlined in the standard operating procedures (SOPs).

Management of pre-existing Studies once the Revised Common Rule Goes Into Effect

The revised Common Rule mandates that studies approved, waived, or exempted before January 21, 2019, will continue to follow the old regulations until their completion Conversely, all protocols approved or exempted on or after January 21, 2019, will adhere to the new rule Currently, Stony Brook University has no plans to transition individual studies from the old rule to the new one after this date.

Research Covered by the Human Research Protection Program

The University’s Human Research Protection Program (HRPP) oversees all research involving human subjects conducted under its auspices This includes studies that are externally funded, supported by internal University resources, or carried out without any direct funding.

Written Policies and Procedures

The University’s Standard Operating Policies and Procedures for Human Research Protection outline the essential regulations for conducting research involving human subjects and the submission process for proposals to the SBU IRB This document is dynamic, with regular updates made by the Assistant Vice President for Research Compliance in collaboration with relevant institutional bodies, including the Institutional Official, Office of Research Compliance staff, Institutional Review Boards, and University counsel The Institutional Official is informed of all significant changes to these policies and procedures.

The Assistant Vice President for Research Compliance will ensure that the University research community stays informed about updates affecting the human research protection program, including relevant laws, regulations, policies, and emerging ethical and scientific issues This information will be accessible on the University’s Human Research website, and copies of the policies and procedures can be requested.

Human Research Protection Program Organization

The Human Research Protection Program (HRPP) is a comprehensive framework designed to safeguard human subjects involved in research It encompasses various roles and entities, including the Institutional Official (IO), the Assistant Vice President for Research Compliance, the Office of Research Compliance (ORC), and the Institutional Review Board (IRB), along with additional committees focused on human subject protection, such as the Institutional Biosafety Committee and the Conflict of Interest Committee The primary aim of the HRPP is to ensure that the University adheres to ethical principles and regulatory standards for the protection of human participants in research studies.

The following officials, administrative units and individuals have primary responsibilities for implementing the HRPP

The Vice President for Research (VPR) holds the ultimate responsibility for the Human Research Protection Program (HRPP), with the Assistant Vice President for Research Compliance acting as the Institutional Official (IO) The IO serves as the main liaison with the Office for Human Research Protections, the Department of Health and Human Services, and the Food and Drug Administration In collaboration with the VPR, the IO is tasked with comprehensive oversight of the program.

The effective development, management, and evaluation of policies and procedures are essential for ensuring compliance with state and federal regulations governing research This involves actively monitoring changes in regulations related to human research protection and overseeing all facets of the Human Research Protection Program (HRPP).

 The Institutional Review Board and University Investigators, ensuring that all are appropriately knowledgeable to conduct research in accordance with ethical standards and applicable regulations

 Keeping other appropriate institutional officials apprised on key matters regarding research at the University

 Implementation the University’s HRPP policy

 Submission, implementation and maintenance of an approved FWA through the

Department of Health and Human Services Office of Human Research Protection (OHRP)

The assessment of the University’s Human Research Protection Program (HRPP) encompasses a thorough evaluation of its resources, including adequate staffing that aligns with the scale and intricacy of the research initiatives It also examines the availability of suitable office and meeting spaces, along with essential equipment, materials, and technology Additionally, the assessment focuses on resources dedicated to the production, maintenance, and secure storage of HRPP and Institutional Review Board (IRB) records, as well as those required for auditing, compliance activities, and the investigation of any instances of noncompliance.

D a t e : 3 / 1 9 / 2 0 2 0 o Access to legal counsel; and o Ensuring that the IRB, investigators, and staff receive training related to human research protections

 Ensuring assistance for investigators in their efforts to carry out University’s research mission

 Development and implementation of needed improvements and ensuring follow-up of actions, as appropriate, for the purpose of managing risk in the research program

 Development of training requirements as required and as appropriate for investigators, subcommittee members and research staff, and ensuring that training is completed on a timely basis

The University's Human Research Protection Program (HRPP) collaborates with University Counsel to interpret and apply New York State law, as well as relevant laws from other jurisdictions, in relation to human subject research.

The investigator serves as the primary protector of human subjects in research, adhering to the highest ethical standards and the principles outlined in the Belmont Report They must conduct research according to an approved protocol, supervise support staff, and ensure the informed consent process is properly managed, unless a waiver is granted by the IRB Maintaining open communication with all research participants is essential Additionally, the investigator must comply with all regulatory policies and institutional requirements, ensuring that research staff receive appropriate training and all necessary approvals are obtained before starting the research When using investigational drugs or devices, the investigator must either cede oversight to the research pharmacy or establish written procedures for their storage, security, dispensing, and disposal.

1.10.4.1 Office of Sponsored Programs (OSP)

The Office of Sponsored Programs (OSP) conducts thorough reviews of all research grants and agreements from federal, foundation, for-profit, and non-profit sponsors This institutional review process guarantees that the terms of each award comply with both institutional and federal policies, ensuring proper oversight and adherence to regulations.

On March 19, 2020, individuals within the Office of Sponsored Programs (OSP) possess the authority to approve and submit research proposals, as well as to execute research grants and agreements for the University To enhance oversight, OSP maintains internal documents during the application process for extramural funding, which include details on Institutional Review Board (IRB) approval status and disclosures of investigator conflicts of interest.

When a grant or contract involves human research activities conducted by external investigators, the University executes a subcontract with the collaborating institution This subcontract mandates that the collaborating institution ensures adherence to federal regulations for the protection of human subjects in research In cases of unfunded collaborations, while a subcontract is not established, the Office of Sponsored Programs (OSP) still verifies compliance by obtaining necessary documentation, such as the collaborating institution's IRB approval.

Pharmacists from the Investigational Drug Service (IDS) at the University’s Hospital Pharmacy Department play a crucial role as consultants and members of the Institutional Review Board (IRB) They receive comprehensive minutes and correspondence from all IRB meetings, ensuring the Pharmacy is fully informed about all IRB-approved research conducted at the University This collaboration allows pharmacists to effectively communicate information regarding studies involving investigational drugs to the Pharmacy staff Additionally, the University’s Hospital Pharmacy and Therapeutics Committee is kept informed about drug-related research reviewed by the IRB, fostering a cohesive approach to managing research and drug safety.

The Investigational Drug Service (IDS) manages the storage, dispensing, labeling, and distribution of medications for human research at the University Hospital, Health Science Center, Cancer Center, and Ambulatory Surgery building Additionally, the IDS evaluates and approves drug storage and distribution plans for human research conducted at other campus locations.

When a patient is admitted to the hospital as an inpatient and is involved in a research protocol that includes medication, it is essential for the Pharmacy to obtain all relevant study materials from the Principal Investigator (PI) This allows the patient to maintain their participation in the study during their hospital stay The Pharmacy will evaluate the protocol and, after consulting with the Assistant Vice President for Research Compliance and applicable Institutional Review Boards (IRBs), will determine if the patient's continued involvement in the study is appropriate.

The Pharmacy is available to provide guidance to investigators in relation to the management of the study drugs

The Office of Clinical Trials at Stony Brook University Hospital aims to simplify industry-sponsored clinical trials by serving as a single point of contact for industry sponsors Its primary functions include facilitating communication and collaboration between sponsors and the hospital to enhance the efficiency of the clinical trial process.

 Match trials to appropriate investigators

 Help find resources for those investigators who lack support

 Review and/or create budgets for assessment and identification of study procedures, study visits, etc

 Negotiate budgets with sponsors/Clinical Research Organizations

 Assist investigators with funding proposals, IRB, and regulatory submissions, if requested

 Collaborate with the Office of Sponsored Programs regarding CTA/Payment terms

 Collaborate with the Office of Grants Management regarding payments received

 Advertise current studies enrolling subjects for recruitment purposes

 Track enrollment of subjects on Cerner/PowerTrials and OCT database

 Manage Clinical Trials Management System (CTMS)

 Provide Study Coordinator services, if requested

 Mentor new investigators and study coordinators

Institutional Review Boards (IRBs) operate independently while coordinating with other University regulatory committees They determine the approval or disapproval of research protocols based on the adequacy of protection for human subjects The IRB oversees all research involving human subjects that is conducted or regulated by federal departments or agencies adhering to human subject regulations Even if research is approved by the IRB, it may still be subject to review by University officials, who cannot approve any research that has not received IRB approval.

The Clinical Trials Compliance Group convenes quarterly to facilitate communication among essential HRPP entities involved in clinical trials Membership includes representatives from Hospital Finance, the Cancer Center, the Office of Sponsored Programs, the Office of Research Compliance, the Office of Clinical Trials, Hospital Compliance, and other relevant areas The group evaluates existing clinical research practices to enhance effectiveness and recommend improvements, ensuring proper conduct and ongoing compliance of clinical trials at the University.

Human Research Protection Program Operations

In addition to the leadership structure described above, support staff members who dedicate 100% effort to the HRPP include, four (4) IRB Administrators and two (2) full-time IRB

Assistants See below for other individuals who contribute significant effort to the protection of human subjects at the University

1.11.1 Assistant Vice President for Research Compliance (AVP-RC) and Staff of the Office of Research Compliance

The Office of Research Compliance (ORC), part of the Office of Vice President for Research (OVPR), is led by an Assistant Vice President for Research Compliance (AVP-RC) and supported by a dedicated team of eight staff members This office is responsible for delivering essential administrative support for the effective management of research compliance activities.

The ORC staff report to the AVP-RC, who supervises their activities In relation to the HRPP, the AVP-RC acts as the Institutional Official (IO), providing overall oversight and implementing the responsibilities outlined in section 1.10.1.

The staff of ORC that is specific to SBU’s HRPP consists of:

Three and a half full-time equivalent (FTE) Institutional Review Board (IRB) Administrators play a crucial role in managing the IRB process for research proposals involving human subjects Their responsibilities encompass the pre-review of documents, screening research proposals before IRB evaluation, assigning reviewers, and acting as a liaison between researchers and the IRB.

On March 19, 2020, investigators and Institutional Review Board (IRB) Administrators collaborated to ensure thorough documentation of discussions, including any controversial topics and actions taken during IRB meetings Each full-time equivalent (FTE) IRB Administrator participates as a voting member on one of the two IRBs and serves as an alternate on the other These administrators are responsible for drafting or overseeing communication between the IRB and investigators.

The IRB Assistant plays a crucial role by delivering administrative support to IRB Administrators, focusing on managing exemptions and facilitating the review and assignment of reviewers for expedited studies.

 1 FTE HRPP Administrator (Research Subject Advocate, Sponsor-Investigator IND/IDE Support, Reliance Administrator, Community Outreach)

 1 FTE HRPP Assistant (assists with research subject advocacy, reliance agreements and community outreach)

 5 FTE QA Administrator (for-cause, not for cause audits, HRPP researcher and institutional COI

The campus community benefits from dedicated clerical support staff who manage all CITI and HRPP-related training initiatives This role involves triaging communications between external entities and the Office of Research Compliance (ORC) members, ensuring efficient support and coordination.

The AVP-RC serves as the Human Protections Administrator under the Federalwide Assurance (FWA), collaborating with an Assistant Director Together, they also oversee the administration and management of the Institutional Animal Care and Use Committee within the Office of Research Compliance (ORC).

The Institutional Biosafety Committee (IBC), along with the Dual Use Research of Concern (DURC), Radioactive Drug Research Committee (RDRC), and Stem Cell Research Oversight committees, play crucial roles in ensuring research compliance and safety The Assistant Vice President for Research Compliance (AVP-RC) also serves as the Research Integrity Officer (RIO), overseeing investigations into research misconduct allegations at the University.

The additional ORC Assistant Director oversees Export Controls, Investigator Conflicts of Interest (COI), and Responsible Conduct in Research and Scholarship This role involves assisting with research misconduct allegations and proceedings, as well as supporting the AAHRPP re-accreditation processes Additionally, this individual collaborates closely with the QA IRB Administrator to manage COI related to human research.

The IRB staff is readily available to assist investigators through phone or in-person consultations, especially for those submitting their proposals for the first time Individual meetings are highly encouraged to help navigate the IRB process effectively.

The Office of Research Compliance is structured to provide administrative support for various compliance committees, ensuring that all necessary compliance approvals are efficiently obtained for specific research activities.

1.11.2 Selection, Supervision and Evaluation of HRPP Supporting Staff

Selection Process: Policies and procedures of the Research Foundation of SUNY and SUNY, are followed for the recruitment and selection of HRPP professional and clerical staff The

The University is committed to being an Affirmative Action and Equal Opportunity employer and educator Hiring departments collaborate with the search committee and Human Resources Recruitment, alongside the Office of Diversity/Affirmative Action, to ensure equitable recruitment practices.

The Affirmative Action/Equal Employment Opportunity Committee is committed to showcasing the University’s sincere efforts in seeking and evaluating a diverse range of applicants This includes qualified individuals from underrepresented groups such as people of color, women, individuals with disabilities, and special disabled or Vietnam era veterans.

When selecting HRPP staff, it's essential to consider factors such as prior experience in IRB administration or related roles, like study coordinator For assistant or clerical positions, a strong desire to learn and actively engage in the regulatory, ethical, and procedural components of an HRPP is also crucial.

The IRB Assistant operates under the supervision of the IRB Administrators, who are accountable to the Assistant Director of the Office of Research Compliance (ORC) The Assistant Director reports directly to the Associate Vice President (AVP).

Evaluation: Research Foundation and SUNY policy requires that a written evaluation and performance program be completed for its employees on an annual basis

The program is designed to:

Human Research Protection Program Resources

The Office of Research Compliance (ORC) is situated in the Melville Library on the Main Campus of the University It is fully equipped with essential office space, meeting areas, storage facilities, and necessary equipment to effectively support the functions of the Human Research Protection Program (HRPP).

The Institutional Office (IO) is responsible for providing the necessary resources to the Institutional Review Boards (IRBs) and the Office for Research Compliance (ORC) This includes ensuring sufficient meeting and office space, as well as staffing to support IRB operations Additionally, essential office equipment and supplies, such as technical support, file cabinets, computers, software, laptops, internet access, and copy machines, are readily available for the IRBs and ORC staff to facilitate their work effectively.

The adequacy of personnel and non-personnel resources within the HRPP program, including IRB committees and ORC, is evaluated annually by the AVP-RC This assessment involves consultations with the Director of Grants Management, the Financial Administrator of ORC, and relevant representatives from other administrative units The Institutional Official (IO) is informed of the assessment results for any necessary follow-up actions.

Conduct of Quality Assurance/ Quality Improvement Activities for the IRB Operation

The University’s HRPP Quality Assurance/Quality Improvement Plan aims to enhance the effectiveness, quality, and compliance of human research protection in alignment with organizational policies and relevant laws This plan will be overseen and executed by the AVP-RC.

Directed audits of research studies approved by any SBU-recognized IRB are initiated in response to issues identified by the IRB, ORC, or complaints from subjects, investigators, or other parties These audits are conducted by the QA Administrator and may involve additional ORC staff, IRB members, or other relevant individuals as needed.

Auditors conducting directed audits may review various materials based on the specific issue under investigation, including research records held by investigators, patient medical records, financial disclosure forms, and other relevant activities as determined by Institutional Review Boards (IRBs).

For each active study undergoing ongoing review, the ORC staff conducts a not-for-cause review This process requires that continuing review submissions include copies of the consent, permission, or assent documents signed by the most recently enrolled subject.

On March 19, 2020, it is essential to redact the subject's signature and name while retaining all dates and the name of the consent-obtaining individual For studies classified as having more than minimal risk, redacted copies of the inclusion/exclusion (I/E) checklist for the last enrolled subject must be provided Random audits of source documents supporting the completed I/E checklist are conducted to ensure correct version status, accurate completion, and the identity of the consent-obtaining individual, confirming their status as an approved investigator and that their human research training is current Any non-compliance identified during these routine not-for-cause reviews will be presented at the next scheduled IRB meeting for committee evaluation.

NOTE: SBU HRPP also has a formal consent monitoring program See SOP section

External directed audits, also known as "for cause" audits, will be conducted on activities at non-University sites where the IRB acts as the "IRB of Record." These audits are initiated to address concerns about compliance with federal, state, and local laws, as well as to ensure the safety of research subjects and adherence to IRB policies and procedures The audits may encompass various activities related to these compliance issues.

Noncompliance identified through directed audits and not-for-cause reviews will be reported to the AVP-RC and the relevant IRB at their next scheduled meeting For studies overseen by external IRBs, reporting will take place at the next on-site IRB meeting If the noncompliance pertains to an investigator and is not specific to a study, all impacted IRBs will be informed of the findings Any noncompliance will be addressed in accordance with the procedures outlined in these SOPs.

In cases where an audit or review uncovers significant or ongoing noncompliance, or if subjects are found to be at risk of unsafe conditions, the Institutional Official (IO), Associate Vice President for Research Compliance (AVP-RC), and/or the Institutional Review Board (IRB) Chair are empowered to take immediate action to safeguard the health and welfare of study subjects, even before the IRB conducts a further investigation.

The AVP-RC, ORC staff, and relevant officials review audit findings to assess if investigators require further education or guidance to enhance the compliance and ethical conduct of their research activities This process also evaluates whether study applications need clarification or revision to ensure adherence to regulations.

The AVP-RC reviews all on-site IRB minutes and meeting documents to ensure proper documentation of discussions and appropriate actions taken This review verifies that federal approval criteria are met, quorum is maintained, conflicts of interest are managed correctly, and conflicted members recuse themselves appropriately Additionally, it assesses the committee's actions on substantive modifications, ensures documented protocol-specific protections for vulnerable populations, and evaluates the quality of IRB member reviews.

The IRB staff is responsible for ensuring that there are no lapses in approval during continuing reviews In the event of a lapse, they will require a report from the Principal Investigator (PI) outlining the activities that occurred during this period Any such activities will be reviewed at the next IRB meeting to assess noncompliance Additionally, the staff will confirm other IRB approvals and Federal Wide Assurances for collaborating institutions or external performance sites, particularly when federal funding is involved.

 The AVP-RC and IRB staff routinely review HRPP standard operating procedures and other documents to ensure consistency with practice

 Other monitoring or auditing activities will be conducted as deemed appropriate by the AVP-RC, and/or IO

The AVP-RC, in collaboration with IRB Chairs and staff, continuously establishes targeted measures for operational efficiency, effectiveness, and compliance within the HRPP To assess the achievement of these goals, the AVP-RC regularly reviews data and implements necessary changes, such as conducting education and modifying processes The IO and IRBs are updated on relevant outcomes, which often lead to targeted educational opportunities for the campus community.

Multi-site Research

When conducting non-exempt human subjects research, particularly in multi-site studies with external collaborators or involving multiple IRBs, the University recognizes its obligation to protect the rights and welfare of participants while adhering to federal regulations The University has the discretion to review the entire research project, focus on specific components, rely on another qualified IRB's review, or implement alternative strategies to minimize redundancy Additionally, when the University holds the primary award for an HHS grant, it is committed to ensuring compliance with these standards.

D a t e : 3 / 1 9 / 2 0 2 0 one IRB reviews the research in its entirety (see section 17.16 regarding the single IRB requirement for multicenter grants awarded from NIH, where all sites are conducting all research procedures)

When collaborating with an external organization or investigator, it is essential to establish a formal relationship through an IRB Authorization This is crucial when relying on another Institutional Review Board (IRB) or acting as the reviewing IRB for outside parties.

Before the University can accept any human research proposals from external organizations or investigators, a written agreement, such as a Memorandum of Understanding, must be executed This agreement is essential for the University to rely on the review conducted by an external Institutional Review Board (IRB).

IRB reliance agreements define the roles and responsibilities of both the reviewing IRB and the relying organization, outlining procedures for communication, information-sharing, and reporting The Reliance Administrator in the Office of Research Compliance uses a checklist to verify that these agreements meet all requirements and align with the University’s standards To promote compliance, the University strives for consistency across all reliance agreements.

The University has officially signed the SMART IRB joinder agreement, enabling participating organizations to request and document IRB reliance through the SMART IRB online platform For each study, the University will assess whether to use SMART IRB standard operating procedures or alternative methods, establishing reliance arrangements between the relying and reviewing sites.

To ensure a smooth grant or contract process, requests for SBU to utilize an external IRB or to act as the IRB of record for an external organization or investigator should be submitted as early as possible This can be done by following the reliance request instructions outlined in section 17.16 of the SOPs.

See section 17.16 for procedures and considerations involved in IRB reliance arrangements

When the SBU Principal Investigator (PI) leads a multi-site or collaborative research project, it is essential to document the communication of the research plan and human subjects protection issues among all participating sites and investigators This includes obtaining initial and continuing IRB approvals, reporting unanticipated problems, implementing study modifications, and sharing interim reports.

SBU's electronic management system facilitates web-based protocol sharing and collaboration among participating sites, streamlining the IRB's initial, continuing, and post-approval reporting submission requirements During the pre-review process, ORC staff plays a crucial role in ensuring compliance and thoroughness.

On March 19, 2020, the Principal Investigator (PI) or designated responsible party from each collaborating site can access the study through the electronic management system, enabling them to stay updated on the study's status and maintain effective reporting capabilities.

Policy

The University has an on-site Institutional Review Board (IRB) appointed by the Institutional Official (IO) to oversee human research The IRB is responsible for prospectively reviewing and making decisions on all non-exempt human research conducted at the University’s facilities or by its employees and agents.

The Institutional Review Board (IRB) at the University is dedicated to safeguarding the rights and welfare of human research subjects It fulfills this responsibility by adhering to the Common Rule, FDA regulations, and other pertinent federal and state regulations, along with the Federalwide Assurance (FWA) and University policies All non-exempt human subjects research conducted under the University's auspices is subject to these rigorous standards.

University must be reviewed and approved by an authorized IRB prior to the initiation of the research

The University also routinely utilizes the services of three off-site IRBs They are:

 Advarra: the Advarra IRB is required to be used by University investigators who wish to conduct industry-initiated, industry-funded research activities

 National Cancer Institute’s Adult CIRB: for applicable cooperative oncology group protocols involving adult subjects

National Cancer Institute’s Pediatric CIRB: for applicable cooperative oncology group protocols involving minor subjects

The University has established multiple Institutional Review Boards (IRBs) to ensure compliance with research protocols, all of which adhere to uniform policies and procedures This article outlines the authority, responsibilities, and operational procedures of the on-site IRBs.

IRB Authority

Under University policy P202R “Research Involving Human Subjects”, the IRB is authorized to:

Human subjects research activities, including exempt research under 45 CFR 46.104, must be approved, modified for approval, or disapproved by the Institutional Review Board (IRB) Limited IRB review is necessary for certain exempt research activities as stipulated in 45 CFR 46.104(d)(2)(iii).

 To require that informed consent is obtained and documented in accordance with regulatory and policy requirements unless the criteria for the waiver or alteration of such

On March 19, 2020, the Institutional Review Board (IRB) confirmed that all requirements were met and approved The IRB may mandate the provision of additional information to participants if it deems that such information would significantly enhance the protection of their rights and welfare.

Research subject to the Common Rule must undergo a continuing review by the convened IRB at intervals that reflect the research's risk level, ensuring that reviews occur at least annually.

Research subject to regulations such as the pre-2018 Common Rule, FDA, or DoJ, as well as specific grant or contract terms, must undergo continuing reviews These reviews should occur at intervals that correspond to the level of risk associated with the research, ensuring that they are conducted at least once a year.

 Suspend or terminate approval of research involving human subjects not being conducted in accordance with University’s IRB requirements or that has been associated with unexpected serious harm to subjects;

 Observe, or have a third party observe, the consent process; and

 Observe, or have a third party observe, the conduct of the research

Research approved by the Institutional Review Board (IRB) may still face additional review and potential disapproval by university officials These officials cannot approve studies that lack IRB approval They may impose stricter requirements or modifications to secure university approval or that of other committees Any university-driven changes to IRB-approved research must be reviewed and approved by the IRB, which will decide if the modifications necessitate a full or expedited review in consultation with the IRB chair.

Number of IRBs

There is currently one (1) on-site and three (3) off-site IRBs that may review research under the auspices of the University

The AVP-RC, in collaboration with IRB staff and IRB Chairs, will conduct an annual review of IRB activities to assess the necessary number of IRBs for the University This assessment will consider the volume and nature of research activities managed by the IRBs.

Roles and Responsibilities

The University Institutional Official appoints the IRB Chairs Any change in appointment, including reappointment or removal, requires written notification

An IRB Chair must be a highly respected individual within the University, skilled in managing the IRB and addressing matters with fairness and impartiality The responsibility of fostering the IRB's reputation within the institutional community lies jointly with the AVP-RC and the IRB Chairs Primarily, the IRB Chairs are tasked with ensuring that the IRB is viewed as fair and impartial, free from influence by the University’s administration, investigators presenting their protocols, and other external sources.

The IRB Chairs are responsible for conducting the meetings and delegates to the IRB

Administrators and Assistant (all IRB members) the responsibility of being signatory for correspondence generated by the IRB

The AVP-RC will conduct an annual review of the IRB Chairs' performance, offering feedback on their adherence to the IRB's mission and policies Chairs who fail to comply with these standards, exhibit excessive absences, or neglect their responsibilities may face removal from their position.

The IRB Chair, or designated IRB Administrators, has the authority to appoint subcommittees to assist in reviewing and executing various IRB functions These subcommittees are responsible for making recommendations to the IRB as needed Additionally, the IRB Chair or the IRB Administrators will select members to participate in each subcommittee, ensuring effective oversight and collaboration within the IRB.

Subcommittee created under this Section The number and composition of the IRB

Membership of the IRB

IRB members are chosen to ensure a diverse representation, taking into account factors such as race, gender, and cultural backgrounds This selection process also addresses specific community concerns and includes professionals from various fields who possess the necessary knowledge and experience to work with vulnerable populations.

On March 19, 2020, the composition of the Institutional Review Board (IRB) is crucial for effectively reviewing research It is essential to include both scientific and non-scientific members to ensure diverse perspectives The IRB's structure must align with the nature and scope of the research conducted at the University, aiming for representation from various specialties relevant to the studies being reviewed.

The IRB must include knowledgeable and experienced members when reviewing research involving vulnerable subjects, such as children, prisoners, and individuals with impaired decision-making abilities or those who are economically or educationally disadvantaged This ensures that the review process addresses the potential for coercion or undue influence Additionally, pregnant women are classified as a vulnerable population under FDA regulations.

The Institutional Review Board (IRB) plays a crucial role in protecting the rights and welfare of human subjects by ensuring adherence to its guidance and recommendations It is essential for the IRB to maintain the professional expertise required to effectively evaluate and oversee various research activities.

Individuals from the Offices of Sponsored Programs, Grants Management, Proposal

Members of the IRB cannot include individuals from Development or Technology Transfer, nor can they participate in the daily operations of the review process However, personnel from these offices may offer information to the IRB and attend meetings as guests.

Composition of the IRB

1 The IRB will have at least five members with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the University

The Institutional Review Board (IRB) will be composed of qualified members with diverse backgrounds, including race, gender, and culture, ensuring sensitivity to community attitudes This diversity enhances the IRB's credibility and effectiveness in protecting the rights and welfare of human subjects.

The Institutional Review Board (IRB) is equipped with the professional expertise required to evaluate specific research activities while ensuring compliance with University policies, applicable laws, and professional standards To achieve this, the IRB will comprise individuals who possess in-depth knowledge in these critical areas.

The Institutional Review Board (IRB) will consist of members with expertise in working with vulnerable populations, such as children, prisoners, individuals with impaired decision-making capacity, and economically or educationally disadvantaged individuals, ensuring their protection in research Additionally, for studies regulated by the FDA, pregnant women are recognized as a vulnerable group requiring special consideration.

The IRB will be composed of a balanced representation of both men and women, ensuring that gender does not influence the selection process, in compliance with FDA requirements Additionally, the IRB will include members from diverse professional backgrounds to avoid a homogeneous composition.

6 The IRB includes at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas

The Institutional Review Board (IRB) must consist of at least one member who is independent from the University and does not have any familial ties to individuals affiliated with it.

8 The IRB includes at least one member who represents the general perspective of subjects

9 One member may satisfy more than one membership category

10 IRB Staff of the ORC may be voting members of the IRB.

Appointment of Members to the IRB

The need for a new or replacement member, or alternate member for the IRB can be identified by the IRB Chairs, AVP-RC, ORC staff, IRB membership, or Institutional Officials Nominations for candidates may come from these individuals, department chairs, or other relevant University officials.

RC evaluates the suitability of the candidate by consulting with IRB Chairs and ORC Staff, considering their qualifications, reputation, and the specific needs of the committee.

Where there are no nominees, appropriate department chairs, program directors, or other University officials will be contacted in writing for candidate nominees by the AVP-RC

The final decision for appointing a new member rests with the IO, with appointments lasting for a renewable two-year term Members have the option to resign by providing written notice to the AVP-RC or IO, and may also be removed for cause by the appropriate authorities.

Each year, the IRB Chair, IRB Staff, and the AVP-RC, representing the Institutional Official, conduct a review of the IRB's membership and composition to ensure compliance with regulatory and institutional standards.

Alternate Members

Alternate members of the IRB share the same appointment process and responsibilities as primary members, bringing comparable expertise and perspectives Their primary role is to act as voting members when regular members are unavailable for convened meetings When stepping in for a primary member, alternate members receive and review the same materials prior to the IRB meeting, ensuring consistency in the decision-making process.

The IRB roster specifies the primary members for whom alternate members can serve as substitutes Alternate members are only considered voting members in the absence of the primary member Documentation in the IRB minutes will record instances when an alternate member steps in for a primary member.

IRB Member Conflict of Interest

Members of the IRB, including regular, alternate, ex officio, and consultants, must not participate in the review of any research project where they have a conflict of interest (COI), except to provide requested information Each IRB member is responsible for disclosing any COI related to a study under review and must recuse themselves accordingly During convened meetings, the member must leave the room to refrain from deliberations and voting Additionally, any reviewer—whether primary, secondary, or expedited—who identifies a COI is required to inform the IRB staff for protocol reassignment.

All voting, alternate, and ex officio members of the IRB complete a “IRB Member Human

Upon initial appointment and annually thereafter, individuals must complete the "Research Conflict of Interest Assessment Form." For comprehensive guidelines on managing conflicts of interest, refer to Section 14, "Conflicts of Interest in Research." The AVP-RC or their designee notifies IRB staff regarding any member's significant financial interests, ensuring appropriate management of review assignments.

Committee members and consultants may find themselves with any of the following COIs when reviewing research:

 Where the IRB member or consultant is involved in the design, conduct, and reporting of the research

 Where an immediate family member of the IRB member or consultant is involved in the design, conduct, and reporting of the research

 Where the IRB member holds significant financial interests (See Section 14 for a definition of significant financial interests) related to the research being reviewed

 Any other situation where an IRB member believes that another interest conflicts with his or her ability to deliberate objectively on a protocol

During each convened meeting, the IRB Chair will survey members to identify any conflicts of interest (COI) related to the protocols under review Members with a COI must recuse themselves by exiting the room during discussions and votes on the relevant protocol Additionally, those with a COI will not be included in the quorum count, and all recusals will be documented in the meeting minutes.

If the COI status of a IRB member changes during the course of a study, the IRB member is required to complete an amended “IRB Member Human Research Conflict of Interest

Assessment Form” and submit the completed document to the AVP-RC, who will, in turn advise the IRB Staff of the change

Use of Consultants

The IRB may seek external or internal experts to assist in reviewing protocols requiring specialized scientific or scholarly knowledge beyond the committee's expertise The need for a consultant can be identified before or during the study review The ORC staff ensures timely provision of relevant materials to the consultant once an outside review is deemed necessary If the convened IRB requires expert consultation, the study will be postponed and reviewed at the subsequent meeting.

Consultants' written statements will be archived in the IRB records, while key insights shared during meetings will be captured in the meeting minutes Additionally, written reviews from external reviewers will be stored alongside the study documentation.

The AVP-RC evaluates the Conflict of Interest (COI) policy for IRB members, requiring consultants to formally declare any potential COI before participating in reviews Consultants with a COI, or those whose spouse or dependent child has a COI with the research sponsor, will be excluded from providing consultation.

The consultant's findings will be presented to the entire board for review, either in person or through written communication Those present will offer consultation but will not engage in discussions or observe the voting process.

Individual members may request ad hoc or informal consultations, ensuring the investigator's confidentiality and adherence to the IRB conflict of interest policy, unless the inquiry is sufficiently generic to maintain the anonymity of the principal investigator and the research protocol.

Duties of IRB Members

One week before the scheduled meeting, the agenda, submission materials, protocols, proposed informed consent forms, and other relevant documents are electronically distributed to members for review.

Attendance Requirements of the IRB Members

IRB members are required to attend all scheduled meetings If a member cannot attend, they must notify an ORC staff member promptly For prolonged absences, members can request an alternate by contacting the AVP-RC.

An IRB member planning an extended absence, such as a sabbatical, must inform the IRB at least 30 days in advance to arrange for a suitable replacement This replacement may be temporary or permanent, depending on the decision made by the AVP-RC If the IRB member has a designated alternate, that individual is authorized to serve during the primary member's absence.

Training/ Ongoing Education for the IRB Chair and Members

An essential element of an effective human research protection program is the education of IRB Chairs and members The University is dedicated to offering continuous training and educational resources for IRB members and ORC staff, focusing on ethical issues and compliance with regulatory and University standards for safeguarding human subjects.

New IRB members, including alternate members, will meet with the AVP-RC or designee for a formal orientation/training session At the session, the new IRB member will be given:

 Web links to the SBU Human Research Protection Program and SOPs

 Stony Brook University HRPP Standard Operating Procedures;

 Federal regulations relevant to IRB

 Copy of the IRB Member Module (“What Every New IRB Member Needs to Know”)

In addition to the training session, the IRB members will complete the Biomedical Basic CITI Training

To maintain ethical oversight of human research and ensure that IRB decisions align with current regulations and policies, continuous training is essential for IRB members throughout their tenure This ongoing education encompasses a variety of activities designed to enhance their understanding and effectiveness in their roles.

 In-service training at IRB meetings;

 Copies of appropriate publications and articles;

The AVP-RC is responsible for identifying and disseminating crucial information that impacts the human research protection program This includes updates on laws, regulations, policies, procedures, and emerging ethical and scientific issues, which are communicated to IRB members through email, mail, or during IRB meetings.

The IO will provide support to send as many members of the IRB as are interested in attending the annual PRIM&R conference

IRB staff must complete relevant modules of the CITI Course focused on the Protection of Human Research Subjects and are required to participate in at least one annual conference or webinar, such as PRIMR.

Liability Coverage for IRB Members

The on-site Institutional Review Board (IRB) is established by the State University of New York (SUNY) According to New York State Public Officers Law, section 17, if the criteria outlined in this section are fulfilled, and pending a determination by the Attorney General of New York, the state will defend its employees and officers in civil actions or proceedings in any state or federal court This defense applies to allegations arising from actions or omissions that occurred while the state employee or officer was performing their public duties.

Review of IRB Member Performance

Annually, the following will be conducted:

 The IRB members are surveyed for feedback on the Chair of their committee

 The Chairs provide feedback on the members of their committee

 The IRB Staff provides feedback on the IRB members and Chairs

The IO or designated representative compiles the provided information and attendance records to create evaluations for each member and chair, which are then communicated to them This correspondence expresses gratitude for their ongoing contributions or informs them that their services will no longer be required.

IRB members who are not acting in accordance with the University mission or its policies and procedures may be removed outside of the formal annual evaluation process

The IRB members who are also IRB staff are annually evaluated by the AVP-RC.

Reporting and Investigation of Allegations of Undue Influence

If an IRB Chair, member, or staff member feels pressured by any party, they should confidentially report the matter to the Institutional Official (IO) or the Assistant Vice President for Research Compliance (AVP-RC) The designated official will carry out a comprehensive investigation and implement corrective measures to prevent future incidents.

Policy

All human subjects research conducted under the auspices of the University must meet the criteria for one of the following methods for review:

The IRB will ensure that the research meets all required ethical and regulatory criteria for initial and continuing review and any modifications of approved research

The following describe the procedures required for the review of research by the IRB.

Definitions

Minimal risk refers to the likelihood and extent of harm or discomfort expected in research, which should not exceed what individuals typically experience in everyday life or during standard physical or psychological assessments.

Minor Change: a change, in the judgment of the IRB reviewer, which makes no substantial alteration in:

 Level of risks to subjects

 Research design or methodology (adding procedures that are not eligible for expedited review would not be considered a minor change)

 Number of subjects enrolled in the research

 Qualifications of the research team

 Facilities available to support safe conduct of the research

 Any other factor which would warrant review of the proposed changes by the convened IRB

A quorum is defined as a simple majority of the voting members, which must include at least one individual with a primary focus outside of scientific disciplines In cases where research pertains to an FDA-regulated item, the presence of a licensed physician in the quorum is mandatory.

The suspension of IRB approval refers to a directive from the convened Institutional Review Board or an authorized individual to temporarily halt some or all previously approved research activities Despite the suspension, the protocols remain open and still require ongoing review.

Termination of IRB approval refers to the decision made by the convened Institutional Review Board (IRB) to permanently halt all activities related to a previously approved research protocol Once a protocol is terminated, it is classified as closed and does not necessitate any further continuing review.

Electronic Management System

The University has implemented an electronic management system to streamline the administration of its Institutional Review Boards (IRBs) This system facilitates the electronic management of protocols and documents, allows for online submissions, and enables web-based collaboration and protocol sharing Additionally, it features automatic notifications, electronic signatures, event tracking, and other essential electronic functions As of December, the University mandates electronic protocol submissions.

In 2007, all protocols, including their revisions and renewals, are required to be submitted electronically through the electronic management system, with review decision notifications also issued via this system Detailed instructions for utilizing the electronic management system can be found on the ORC website.

Human Subjects Research Determination

Certain university activities, such as academic classroom interactions and hospital quality assurance or quality improvement initiatives, may involve individuals; however, these activities do not necessarily qualify as human subject research.

Investigators are responsible for determining whether an activity qualifies as human subjects research, relying on the definitions of "human subject" and "research." To avoid potential liability for incorrect determinations, it is advisable for investigators to seek confirmation from the Office of Research Compliance (ORC) regarding their assessments Requests for confirmation should be submitted through the electronic management system and must include adequate documentation to support the activity's classification.

The revised Common Rule has eliminated the requirement from the Newborn Screening Saves Lives Reauthorization Act of 2014 that federally-funded research on newborn dried blood spots be classified as research involving human subjects Now, such research will be assessed using the same criteria applied to other studies involving human biospecimens, considering factors like the identifiability of subjects, specimen coding, access to the key, and whether the research evaluates the safety or effectiveness of FDA-regulated devices.

To address investigator inquiries, any activities deemed not to involve human subjects research will be recorded using the Human Subjects Research Determination form Conversely, if an activity is classified as human subjects research, the investigator will be guided to initiate the appropriate exemption or Institutional Review Board (IRB) application process.

The University maintains a clear policy differentiating between Quality Assurance/Quality Improvement (QA/QI) initiatives and research activities For comprehensive details, please refer to the section titled “Quality Assurance/Quality Improvement (QA/QI) Activities vs Research Activities.”

A case study or series involves the analysis of up to three clinical cases, focusing on aspects such as condition, treatment, presentation, or outcome For analyses that include more than three cases, review by the Human Research Protection Program is required, along with the completion of an application in the electronic management system, myResearch.

A case study or series is not intended to make wide-ranging conclusions about a population and does not fulfill the DHHS definition of research, which defines research as a systematic investigation aimed at developing or contributing to generalizable knowledge through research development, testing, and evaluation.

The use of Protected Health Information (PHI) in case studies does not necessitate Institutional Review Board (IRB) approval; however, the Health Insurance Portability and Accountability Act (HIPAA) mandates written authorization for specific uses and disclosures of a patient's PHI This means that either the patient must sign an Authorization Agreement, or a parent or legally authorized representative must do so if the patient is deceased or unable to consent If these conditions are not met, a waiver from the Stony Brook University Hospital Privacy Board for HIPAA Authorization would be required.

An Authorization Agreement is unnecessary when patient information is non-identifiable, meaning no photographs or distinctive features, such as tattoos or scars, are disclosed Furthermore, the case study information must be general enough to prevent identification by the patient's family or acquaintances.

NOTE: Some journals now require a letter or other form of acknowledgement from the

The Institutional Review Board (IRB) approval is required before submitting a case study or series to a journal For confirmation of Stony Brook University policy, please refer to the memo available at the following link: https://www.stonybrook.edu/commcms/research-compliance/Human-Subjects/sops This memo should be sent to the journal as part of the submission process.

Exempt Studies

All research involving human subjects at SBU requires approval, with certain categories exempt from IRB oversight However, the determination of exempt status must be made by ORC Staff, who are independent from the proposed research and free from conflicts of interest Reviewers will evaluate the submissions accordingly.

Exemption Determination Checklist to determine and document whether the protocol meets the exemption criteria

SBU may also choose to accept an exempt determination made by an external IRB; SBU will consider such requests on a case by case basis

Exempt studies, as defined by law or federal agency heads, are not subject to the Common Rule's requirements for IRB approval and full research consent, except for specific regulations regarding exemptions and limited IRB review However, ethical considerations remain paramount, and researchers must adhere to the principles outlined in the Belmont Report The individual responsible for determining exemption status may impose additional protections for subjects to uphold these ethical standards, such as requiring disclosure or consent.

The exemption remains in effect for the duration of the project or until any changes necessitate an amendment, whichever occurs first Investigators are required to inform the ORC of any proposed changes during the project's execution for review to assess the continued applicability of the exemption Written decisions regarding the exemption status will be communicated to the investigator, including documentation of the specific category or categories that justify the exemption.

Research involving children does not qualify for Exemption #2(i) and (ii) regarding surveys, interviews, or observations of public behavior unless the investigator is not participating in the observed activities Additionally, Exemption #2(iii), which pertains to identifiable information and limited IRB review, is also inapplicable to research with children Furthermore, Exemption #3 does not apply to studies involving child participants [45 CFR 46.104(b)(3)]

Prisoners: Exemptions do not apply except for research aimed at involving a broader subject population that only incidentally includes prisoners [45 CFR 46.104(b)(2)]

Research activities involving human subjects that fall under specific categories may be considered exempt from FDA regulations, provided they comply with applicable laws, regulations, and agency policies For detailed exemptions, refer to Section 3.5.3 regarding FDA guidelines.

For relevant information regarding the activity in question, refer to the Special Topics Section on Data/Tissue Registries/Banks and the Guidance on Research Involving Coded Private Information or Biological Specimens.

 SBU at this time has not adopted Broad Consent and therefore cannot accept applications for exempt categories reviewed under 45 CFR 46.104 (d)(7) and (8)

Research conducted in recognized educational environments focuses on standard practices that do not hinder students' learning opportunities or the assessment of educators This encompasses studies on both regular and special education instructional strategies, as well as evaluations of the effectiveness and comparisons of various instructional techniques, curricula, and classroom management methods.

Research involving educational tests, surveys, interviews, or public behavior observation is permissible if certain criteria are met: 1) the investigator records information in a way that conceals the subjects' identities; 2) any disclosure of subjects' responses poses no risk of legal or reputational harm; or 3) if subjects' identities are identifiable, a limited IRB review ensures adequate privacy protections and data confidentiality as per 45 CFR 46.111(a)(7).

Research involving benign behavioral interventions must include the collection of information from adult subjects through verbal or written responses, or audiovisual recordings, provided that the subjects consent to both the intervention and information collection Additionally, at least one specific criterion must be met to ensure ethical compliance.

The investigator ensures that the recorded information protects the identity of human subjects, making it difficult to identify them directly or through any associated identifiers.

Disclosure of human subjects' responses from the research will not pose any reasonable risk of criminal or civil liability, nor will it adversely affect their financial status, job prospects, educational opportunities, or reputation.

The investigator records information in a way that allows for the identification of human subjects, either directly or through linked identifiers An Institutional Review Board (IRB) performs a limited review to ensure compliance with 45 CFR 46.111(a)(7), confirming that adequate measures are in place to protect subjects' privacy and maintain data confidentiality.

Benign behavioral interventions are characterized by their brief duration, harmlessness, and non-invasive nature, ensuring they do not cause significant adverse effects on participants Investigators must ensure that subjects are unlikely to find these interventions offensive or embarrassing Examples of such interventions include engaging subjects in online games, solving puzzles under different noise conditions, or making decisions on the allocation of a small amount of cash between themselves and another person.

Research that involves deceiving participants about its nature or purposes does not qualify for exemption unless the participants consent to this deception in advance This consent must occur under conditions where they are informed that they will be misled or unaware of the true nature of the research.

Secondary research involving identifiable private information or biospecimens does not require consent if certain criteria are met These criteria include: i) the information or biospecimens are publicly available; or ii) the investigator records the information in a way that prevents easy identification of subjects, does not contact them, and will not attempt to re-identify them.

Expedited Review

The IRB may use the expedited review procedure to review either the following:

Research eligible for expedited review may include various categories, provided that the reviewer assesses and confirms that the research poses no more than minimal risk In cases where the research is subject to FDA regulations, the reviewer must ensure that it also meets the minimal risk criteria.

2 Minor changes (as defined in section 3.2) in research previously approved by the convened IRB Note: review of minor changes does not alter the end-date of study approval

3 Research for which limited IRB review is a condition of exemption under 45 CFR

3.6.1 Categories of Research Eligible for Expedited Review

Activities governed by the Common Rule are generally considered to pose minimal risk if they fall under specific categories However, this presumption can be challenged if a reviewer assesses and documents that the study presents more than minimal risk.

Activities regulated by the FDA should not be considered minimal risk solely due to their inclusion on a specific list This inclusion indicates eligibility for expedited review only when the proposed research presents no more than minimal risk to human subjects It is essential for the reviewer to specifically assess and confirm that the activity meets the criteria for minimal risk.

The categories in this list apply regardless of the age of subjects, except as noted in category 2 below

The expedited review procedure may not be used:

Identifying subjects or their responses may expose them to potential criminal or civil liability, harm their financial status, employability, insurability, or reputation, and lead to stigmatization Therefore, it is crucial to implement reasonable and appropriate protections to ensure that the risks of privacy invasion and confidentiality breaches remain minimal.

 For classified research involving human subjects

Research Categories one (1) through seven (7) pertain to both initial and continuing IRB review:

For relevant information regarding data and tissue registries or banks, refer to Special Topics Section 17.2, and for guidance on research involving coded private information or biological specimens, see Section 17.5.

Clinical studies involving drugs and medical devices can proceed only under specific conditions: either when research pertains to drugs that do not require an investigational new drug application (21 CFR Part 312) or when the study involves marketed drugs that significantly elevate associated risks.

On March 19, 2020, it was noted that certain medical devices are not eligible for expedited review if they decrease the acceptability of associated risks Specifically, research on medical devices does not require an investigational device exemption application under 21 CFR Part 812 if the device is already cleared or approved for marketing and is being utilized in accordance with its approved labeling.

Blood samples can be collected through various methods such as finger stick, heel stick, ear stick, or venipuncture For healthy, non-pregnant adults weighing at least 110 pounds, the maximum amount drawn should not exceed 550 ml within an eight-week period, and collections can occur no more than twice a week For other adults and children, the collection process must consider their age, weight, and health, limiting the amount to the lesser of 50 ml or 3 ml per kg over the same eight-week timeframe, also with a frequency of no more than twice a week.

3 Prospective collection of biological specimens for research purposes by noninvasive means

The article outlines various biological samples that can be collected in a non-invasive manner for clinical or research purposes These include hair and nail clippings, deciduous and permanent teeth during routine care, excreta and external secretions like sweat, saliva collected through unstimulated or stimulated methods, and the placenta at delivery Additionally, amniotic fluid can be obtained during labor, while supra- and subgingival dental plaque and calculus may be collected through standard prophylactic techniques Other samples include mucosal and skin cells from buccal scraping or swabbing, as well as sputum collected after saline mist nebulization.

Data collection through noninvasive procedures, which do not require general anesthesia or sedation, is commonly practiced in clinical settings This excludes methods that involve x-rays or microwaves When utilizing medical devices, these must be cleared or approved for marketing It's important to note that studies aimed at assessing the safety and effectiveness of medical devices typically do not qualify for expedited review, including those evaluating cleared devices for new indications.

Physical sensors can be utilized on the body's surface or from a distance, ensuring minimal energy input and maintaining the subject's privacy These sensors can also be employed to assess weight or evaluate sensory acuity, as well as for magnetic testing.

On March 19, 2020, various diagnostic techniques were highlighted, including resonance imaging, electrocardiography, electroencephalography, and thermography Additional methods such as the detection of natural radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, Doppler blood flow analysis, and echocardiography were also discussed Furthermore, the importance of moderate exercise, muscular strength testing, body composition assessment, and flexibility testing was emphasized, tailored to the individual's age, weight, and health status.

5 Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis)

Certain research studies may not be subject to DHHS regulations regarding the protection of human subjects, as outlined in the Exempt Categories and 45 CFR 46 101(b)(4) This article specifically focuses on research that does not qualify for exemption.

6 Collection of data from voice, video, digital, or image recordings made for research purposes

Research on individual or group characteristics and behaviors encompasses a wide range of topics, including perception, cognition, motivation, identity, language, communication, cultural beliefs, and social behavior This research often utilizes methodologies such as surveys, interviews, oral histories, focus groups, program evaluations, human factors evaluations, and quality assurance techniques to gather and analyze data effectively.

Certain research may be exempt from DHHS regulations concerning the protection of human subjects, as outlined in Exempt Categories and 45 CFR 46.101(b)(2) This information specifically pertains to research that does not fall under these exempt categories.

Categories 8 and 9 only apply to continuing review

Convened IRB Meetings

The IRB is responsible for conducting initial and ongoing reviews of all non-exempt research during convened meetings, ensuring that a quorum of members is present, unless an expedited review procedure is utilized for certain exempt research.

The Institutional Review Board (IRB) convenes weekly year-round, although meeting schedules may change due to holidays or insufficient quorum For detailed information on meeting dates and deadlines, please visit the ORC website.

Special meeting can be called at any time by the IRB Chair, the AVP-RC, or the IO

The ORC staff conducts an initial review of all study materials submitted for IRB evaluation to ensure completeness, accuracy, and compliance with special regulatory requirements, including necessary electronic signatures from the department chair and principal investigator Only submissions that are complete will be scheduled for review on the IRB agenda, and investigators will be informed of any missing information via the electronic management system.

Once a research study submission is deemed complete, the IRB Staff assigns it to reviewers, considering the scientific content of the protocol and the reviewers' areas of expertise to ensure both scientific and non-scientific perspectives are included Each initial or continuing protocol is reviewed by two assigned reviewers, who may also handle multiple protocols or research items In cases where the protocol exceeds the knowledge of the IRB members, an outside consultant will be engaged for additional expertise.

Protocols for which appropriate expertise cannot be obtained for a given meeting will be tabled and moved to a subsequent meeting agenda

The primary and secondary reviewers are responsible for:

1 Having a thorough knowledge of all of the details of the proposed research

2 Performing an in-depth review of the proposed research

During the convened meeting, the discussion of the proposed research was led by presenting both its positive and negative aspects, while guiding the Institutional Review Board (IRB) through the necessary regulatory criteria for approval.

4 Making suggestions for changes to the proposed research, where applicable

5 Completing all applicable IRB reviewer forms

In the event that both the primary and secondary reviewers are unavailable for the meeting, a consensus will be reached to decide whether the study will be postponed for review at a future meeting.

On March 19, 2020, it was confirmed that the current members possess adequate information and expertise to proceed with the review An absent reviewer may submit written comments for discussion during the meeting, provided another reviewer is present to act as the primary reviewer Importantly, all Institutional Review Board (IRB) members are required to review all studies, not limited to those for which they are designated as primary or secondary reviewers.

3.7.4 Pre-Meeting Distribution of Documents

To ensure inclusion on the IRB agenda, all required study materials must be submitted by the specified deadline The IRB Staff will prepare the meeting agenda and provide it to members through the electronic management system prior to the meeting IRB members will have access to protocol review materials at least five business days in advance to facilitate thorough review Additionally, prior meeting minutes, relevant business items, audits, and continuing education materials will be shared with members as early as possible.

3.7.4.1 Investigator Contact Before the Meeting

To enhance efficiency and communication between the IRB and investigators, IRB members are encouraged to reach out to principal investigators (PIs) with any questions or clarifications prior to meetings This proactive approach aims to streamline the review process and reduce the likelihood of deferrals or disapprovals.

3.7.5 Materials to be Submitted for IRB Full Committee Review

Each IRB member will be given access to all submission materials for all studies on the agenda: The following checklists summarize the document requirements for submission to the IRB:

Registration Form and /or Application

Data collection sheets (e.g., spreadsheets, case report forms)

 A: Pregnant Women, Fetuses, Non and Questionably Viable Neonates

Protocol Review Committee (PRC) Approval (oncology studies only)

Fee authorization form (for industry studies going to CRRI)

Scientific merit review (for industry studies going to CRRI or NCI CIRB)

Package inserts for approved drugs/devices

Investigator brochures for investigational drugs/devices

Registration Form and /or Application

Redacted consent/permission/assent documents of last subject enrolled

 Inclusion/exclusion checklist (clean, current)

 Redacted I/E checklist of last subject enrolled

 Data safety monitoring board reports

 Gov’t or sponsor audit/monitoring reports

Before submitting materials to the IRB members, IRB staff will confirm that the application package is electronically signed by the principal investigator and the chair of the departmental review committee Additionally, if the project affects resources from another department, the electronic signature of that department's chair is also necessary.

The electronic management system allows all IRB members to access submitted materials, but primary and secondary reviewers are specifically required to evaluate relevant grant applications, the sponsor's protocol, the investigator's brochure, the DHHS-approved sample informed consent document, and the complete DHHS-approved protocol, when available.

Reviewers will complete the IRB Member Worksheet(s) for Full Committee Review

A quorum for meetings requires a simple majority of the voting members, including at least one individual focused on a non-scientific area In cases involving FDA-regulated research, a licensed physician must be part of the quorum Prior to starting the meeting, the IRB Chair, aided by the IRB staff, will verify the presence of the necessary quorum Additionally, the IRB staff is tasked with maintaining the proper convening of the meetings.

To ensure valid voting, a quorum must be maintained during IRB meetings The IRB staff monitors member attendance and informs the chair if a quorum is absent If a quorum is lost due to a member's recusal from a Conflict of Interest, the proposal must be tabled Additionally, if quorum is not maintained for the rest of the meeting, it must be terminated.

IRB members can be deemed present when participating via teleconference or videoconference, provided they have received all relevant materials ahead of the meeting Active and equal participation in discussions is essential for these members.

Absentee opinions from Institutional Review Board (IRB) members communicated via mail, telephone, facsimile, or email can be taken into account by present IRB members; however, these opinions do not count as official votes and cannot fulfill the quorum requirements for convened meetings.

Criteria for IRB Approval of Research

In order for the IRB to approve human subject research, it must determine that the following requirements are satisfied:

To minimize risks to subjects, procedures are employed that align with sound research design and avoid unnecessary exposure to risk Additionally, whenever feasible, existing diagnostic or treatment procedures are utilized for the subjects involved.

The risks to research subjects must be justified by the anticipated benefits and the potential knowledge gained from the study When assessing risks and benefits, the Institutional Review Board (IRB) should focus solely on those directly associated with the research, rather than the inherent risks or benefits of standard therapies unrelated to the study Additionally, the IRB is not responsible for considering the long-term implications of the research findings, such as their potential impact on public policy.

The selection of research subjects must be fair and equitable, considering the research's objectives and the specific environment in which it will take place The Institutional Review Board (IRB) should be especially aware of the unique challenges associated with the research to ensure ethical standards are upheld.

D a t e : 3 / 1 9 / 2 0 2 0 involving subjects vulnerable to coercion or undue influence, such as children, prisoners, mentally disable persons, or economically or educationally disadvantaged persons

4 Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.117

5 Informed consent will be appropriately documented, in accordance with, and to the extent required by 45 CFR 46.117

6 When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects

7 When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data

When research involves vulnerable populations—such as children, prisoners, individuals with impaired decision-making abilities, or those who are economically or educationally disadvantaged—extra precautions are implemented to ensure their rights and welfare are protected.

The primary objective of the assessment is to confirm that the risks faced by research participants are warranted by the expected benefits to both the individuals involved and society at large To achieve this, the Institutional Review Board (IRB) must carefully evaluate the balance between risks and benefits.

When assessing risks that are considered more than minimal, it is essential to evaluate whether the expected benefits, such as gaining new knowledge or enhancing the health of research subjects, justify the potential risks involved for participants.

2 Not approve research in which the risks are judged unreasonable in relation to the anticipated benefits

The assessment of the risks and benefits of proposed research - one of the major responsibilities of the IRB - involves a series of steps:

1 Identify the procedures being conducted specifically for research;

2 Identify the risks associated with the research procedures, as distinguished from the risks of therapies the subjects would receive even if not participating in research;

3 Determine whether the risks will be minimized to the extent possible;

4 Identify the probable benefits to be derived from the research;

5 Determine whether the risks are reasonable in relation to the benefits to subjects, if any, and assess the importance of the knowledge to be gained;

6 Ensure that potential subjects will be provided with an accurate and fair description of the risks or discomforts and the anticipated benefits

Risks to subjects are minimized:

1 By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk; and

2 Whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes

Risks to subjects are reasonable in relation to anticipated benefits, if any, and to the importance of the knowledge that may reasonably be expected to result

When assessing risks and benefits, the Institutional Review Board (IRB) must focus solely on those associated with the research itself, rather than the risks and benefits related to treatments that participants would receive outside of the study.

The Institutional Review Board (IRB) is not responsible for evaluating the potential long-term impacts of research findings, such as their influence on public policy, as these considerations do not fall under the scope of research risks that the IRB oversees.

In order to assess the risks and benefits of the proposed research, the IRB must determine that:

 The research uses procedures consistent with sound research design;

 The research design is sound enough to reasonably expect the research to answer its proposed question; and

 The knowledge expected to result from this research is sufficiently important to justify the risk

The IRB relies on its own expertise and the insights of others, including departmental reviews by chairs or committees through e-signatures on submissions, as well as the peer review processes of funding agencies, to make informed determinations.

Before the Institutional Review Board (IRB) evaluates new and ongoing protocol applications, along with significant amendments, the institutional scientific review is confirmed through the e-signature of the administrative official overseeing the investigator's research unit.

3.8.2 Selection of Subjects is Equitable

The Institutional Review Board (IRB) evaluates research applications to ensure that the selection of participants is fair and considers factors such as gender, age, and socioeconomic status Studies lacking equitable subject selection or failing to justify the exclusion of certain groups that could benefit from the research will not receive IRB approval.

The Institutional Review Board (IRB) assesses several key factors when determining research approval, including the research's objectives, the environment in which it takes place, and the scientific and ethical rationale for including vulnerable populations such as children, prisoners, and individuals with impaired decision-making capacity Additionally, the IRB considers the justification for excluding certain groups who could benefit from the research, as well as the specific inclusion and exclusion criteria.

During the ongoing review, the Institutional Review Board (IRB) will assess whether the Principal Investigator (PI) has adhered to the subject selection criteria established during the initial IRB review and approval process.

Before utilizing any study recruitment materials, the recruitment plan must receive approval from the Institutional Review Board (IRB) This plan should provide detailed information regarding the media formats (such as flyers, newspapers, videos, or radio), specific locations (including on-campus or off-campus sites), and the conditions under which potential subjects will be approached Investigators must also consider any additional approvals needed for the sites included in the recruitment plan, and these should be submitted to the IRB for their records.

The HRPP policy mandates that initial contact with potential research subjects must be made by individuals who have an established relationship with the patients, such as healthcare providers involved in their treatment This approach respects patients, as they visit the hospital for clinical reasons, ensuring that discussions about research are conducted by familiar and trusted personnel.

Additional Considerations during IRB Review and Approval of Research

During the initial and ongoing review, the Institutional Review Board (IRB) assesses the risks linked to research protocols, categorizing them as either "minimal" or "greater than minimal" based on a strict interpretation of minimal risk The IRB's risk level determinations will be documented in the meeting minutes If the risk is classified as minimal, the IRB will vote on whether the study can undergo subsequent reviews through an expedited process.

The Institutional Review Board (IRB) determines the frequency of research protocol reviews during both initial and continuing evaluations All protocols are reviewed at intervals that reflect their risk level, with a minimum requirement of once per year For research governed by the Common Rule, the IRB conducts ongoing reviews at appropriate intervals based on risk, ensuring compliance with the minimum annual review requirement as outlined in the Standard Operating Procedures (SOPs).

In certain situations, it may be necessary to conduct reviews more frequently, such as biannually or quarterly, or after reaching a specific number of subjects The minutes from the meeting will document the IRB's decision on the review frequency.

3.9.2.1 Review More Often Than Annually

Certain variables may be considered by the IRB in determining those studies that require review more often than annually For example:

 Significant risk to research subjects (e.g death, permanent or long lasting disability or morbidity, severe toxicity) without the possibility of direct benefit to the subjects;

 The inclusion of significantly vulnerable populations where, even in the presence of possible direct benefit, there is also a possibility of significant risk associated with the research procedures

 A history of serious or continuing non-compliance on the part of the PI

 The likely medical condition of the proposed subjects

 The novelty of the research making unanticipated adverse events more likely

 Any other factors that the IRB deems relevant

The Institutional Review Board (IRB) may set an approval period of less than one year, defined by either a specific time frame or a maximum number of subjects to be studied or enrolled If the approval period is based on the number of subjects, it cannot exceed one year unless the study does not require ongoing review When an approval period under one year is designated for research requiring continuing review, the rationale for this more frequent evaluation must be clearly documented in the meeting minutes or the reviewer checklist.

3.9.3 Independent Verification That No Material Changes Have Occurred

The IRB acknowledges the importance of safeguarding the rights and welfare of research subjects, which may necessitate independent verification from sources beyond the investigator to ensure that no significant changes have occurred since the last IRB review This independent verification is particularly crucial in cooperative studies or multi-center research, where reliance on the investigator alone may not suffice.

The IRB will assess the necessity for external verification on a case-by-case basis, taking into account specific factors to determine which studies require independent verification This update reflects changes to the AAHRPP's Evaluation Instrument, and the considerations outlined by AAHRPP (#’s 1-7) are mandatory for FDA-regulated research.

1 The nature, probability, and magnitude of anticipated risks to subjects;

2 The degree of uncertainty regarding the risks involved;

3 Whether the research involves novel therapies or procedures;

4 The vulnerability(ies) of the subject population;

5 The projected rate of enrollment;

6 The experience and expertise of the investigators;

7 The IRB’s previous experience with the investigators or the sponsor (e.g., compliance history, complaints from subjects, etc.);

8 The probable nature and frequency of changes that may ordinarily be expected in the type of research;

9 Whether the research undergoes routine independent monitoring;

10 Whether concerns about possible material changes occurring without IRB approval have been raised based on information provided in continuing review reports or from other sources; and

11 Any other factors that suggest independent verification is warranted

If any material changes have occurred without IRB review and approval, the IRB will assess the issue in accordance with procedures for noncompliance detailed in Section 10

The Institutional Review Board (IRB) regularly evaluates the effectiveness of informed consent procedures in approved studies, as detailed in Section 5.9 Additionally, the IRB may occasionally require special oversight of the consent process by an impartial observer, known as a consent monitor, to mitigate risks of coercion and undue influence.

Monitoring is essential when research poses significant risks to participants or when they may struggle to comprehend the provided information Additionally, it serves as a corrective measure if the Institutional Review Board (IRB) identifies issues related to a specific investigator or research project.

See Section 5.9 for a detailed discussion of consent monitoring

All investigators must adhere to University Policy P209, which mandates the completion of disclosures regarding significant financial interests In cases where such interests are disclosed, both the Institutional Review Board (IRB) and the University Conflict of Interest (COI) Committee will independently evaluate the potential financial conflict of interest and determine if it can be managed according to Public Health Service (PHS) policy The IRB's role in the conflict management plan will prioritize the protection of human subjects In the event of a disagreement between the IRB and COI committees about the sufficiency of a management plan, the IRB's decision will be final For more details, refer to Section 14 on Conflict of Interest.

During research, new findings regarding the medication or test article may arise, necessitating the Principal Investigator (PI) to report these significant developments to the Institutional Review Board (IRB) The IRB will assess the implications of these findings on the subjects' rights and welfare If the new information impacts the risks or benefits for participants or their willingness to remain in the study, the IRB may mandate that the PI inform currently enrolled subjects through a consent addendum Consequently, the informed consent documents must be updated, and the IRB might require re-consenting of participants to confirm their understanding of the new information and their continued involvement in the research.

All advertisements for studies overseen by the IRB must receive prior approval before being posted or distributed The IRB will review all materials to ensure compliance with ethical standards.

1 The information contained in the advertisement;

2 The mode of its communication;

3 The final copy of printed advertisement; and/or

4 The final audio/video taped advertisements

This information should be submitted to the IRB with the initial application or as an addendum to the protocol

The IRB evaluates the material to ensure its accuracy and to prevent any coercive or overly optimistic language that could unduly influence subjects' decisions to participate.

1 Statements implying a certainty of favorable outcome or other benefits beyond what was outlined in the consent document and the protocol

2 Claims, either explicitly or implicitly, that the drug, biologic or device was safe or effective for the purposes under investigation

3 Claims, either explicitly or implicitly, that the test article was known to be equivalent or superior to any other drug, biologic or device

4 Using terms like “new treatment,” “new medication,” or “new drug” without explaining that the test article was experimental

5 Promising “free medical treatment” when the intent was only to say subjects will not be charged for taking part in the investigation

6 Emphasis on payment or the amount to be paid, such as bold type or larger font on printed media

7 The inclusion of exculpatory language

Advertisements for recruiting subjects should focus solely on the essential information needed for potential participants to assess their eligibility and interest Appropriate wording can include key details such as study objectives, eligibility criteria, participation requirements, and potential benefits or risks involved.

1 The name and address of the clinical investigator and/or research facility

2 The condition being studied and/or the purpose of the research

3 In summary form, the criteria that will be used to determine eligibility for the study

4 The time or other commitment required of the subjects

5 The location of the research and the person or office to contact for further information

6 A clear statement that this is research and not treatment

7 A brief list of potential benefits (e.g no cost for a health exam)

Advertisements for trials sponsored by companies will not offer compensation in the form of coupons that provide discounts on the product's purchase price after it receives marketing approval.

Once approved by the IRB, an advertisement cannot be altered or manipulated in any way without prior the IRB approval

Compensation for research participants serves as an incentive for involvement or as reimbursement for expenses like travel; however, it is not classified as a research benefit Researchers must ensure that payments do not lead to coercion, and the compensation should correspond to the level of risk, inconvenience, or discomfort associated with participation Ultimately, the amount of payment must be proportional to the challenges faced by participants in the study.

Investigators who wish to pay research subjects must indicate in their research project application the justification for such payment Such justification should:

1 Substantiate that proposed payments are reasonable and commensurate with the expected contributions of the subject;

2 State the terms of the subject participation agreement and the amount of payment in the informed consent form; and

3 Substantiate that subject payments are fair and appropriate, and that they do not constitute (or appear to constitute) undue pressure on the individual to volunteer for the research study

The IRB must review both the amount of payment and the proposed method of disbursement to assure that neither entails problems of coercion or undue influence

Possible IRB Actions

During its research review process, the Institutional Review Board (IRB) can undertake various actions, which apply to both expedited and convened board reviews, including limited IRB reviews However, disapproval of a study can only occur during a convened IRB meeting.

Approval: The study is approved as submitted

To obtain approval, specific modifications must be made, necessitating agreement from the Principal Investigator (PI) These revisions may include minor wording changes, with suggested replacements provided, or the PI's confirmation of the Institutional Review Board's (IRB) understanding of a specific issue.

For studies undergoing full review, the needed revisions are agreed upon at the meeting; for those undergoing expedited review, they are designated by the reviewer(s)

In order to receive approval for a protocol requiring modifications:

In full review studies, the IRB staff triages the investigator's response, revised protocol, and previously submitted protocol to determine if a final reviewer was designated during the initial meeting If no specific reviewer was assigned, IRB members will either conduct the final review themselves or collaborate with the IRB Chair or a subcommittee, including primary and/or secondary reviewers The reviewer(s) have the authority to approve the study based on the revised materials without requiring additional action from the IRB.

 For expedited studies, the investigator’s response, and all other materials will either be returned to the original reviewer, or handled by IRB staff

Approval of the protocol application will not be granted and certification will not be issued until all deficiencies, if any, are corrected to the satisfaction of the final reviewer(s)

The results of the IRB or expedited reviewer's discussions are communicated to the investigator in writing, with all deliberations documented in the meeting minutes and stored in the electronic study file for both full and expedited studies.

The expiration date for the protocol is determined by the date the convened Institutional Review Board (IRB) conducted its review, rather than the date of final approval.

Deferral (Expedited Review): If an expedited reviewer defers a study, the IRB Staff will place it on the agenda for the next IRB meeting

A deferral indicates that significant changes to the submission must be made before approval can be granted This action is necessary when substantial modifications or clarifications are needed, or when the information provided is inadequate to properly evaluate the protocol application, such as when the risks and benefits cannot be assessed The Institutional Review Board (IRB) will not approve the proposed research until it has conducted a subsequent review of the materials submitted by the Principal Investigator (PI).

In order to receive approval for a protocol deferred for substantive issues:

For a comprehensive review, the investigator's response must be presented at a future convened meeting of the same Institutional Review Board (IRB) The Office of Research Compliance (ORC) supplies the IRB with this response, ensuring that all previous and new materials are accessible to members through the electronic management system The item will then be included in the agenda for re-evaluation at the next meeting.

Approval of the protocol application will not be granted and certification will not be issued until all deficiencies, if any, are corrected to the satisfaction of the IRB

The outcome of the IRB's deliberations is communicated to the investigator in writing

The IRB's determination concerning the subsequent amended submission will be documented in the minutes of the IRB meeting

The Institutional Review Board (IRB) has concluded that the proposed research is not permissible at the University or by its employees or agents Such disapprovals are made during full committee meetings and cannot be decided through expedited review processes.

Tabled: The IRB is unable to review the research at the convened meeting (e.g., due to incomplete submission, loss of quorum, etc.).

Study Suspension, Termination

IRB approval can be suspended or terminated if research fails to comply with IRB or regulatory standards, or if it leads to unexpected issues or serious harm to participants For more details on unexpected problems, refer to Section 8.

The IRB has the authority to suspend or terminate any research that requires its approval, which includes exempt studies that undergo limited review and research that no longer needs ongoing evaluation.

The suspension of IRB approval, directed by the convened IRB, IRB Chair, AVP-RC, or the IO, temporarily halts some or all previously approved research activities while keeping the protocols open for continuing review In contrast, the termination of IRB approval is a directive from the convened IRB to permanently cease all activities associated with a previously approved research protocol, resulting in terminated protocols being considered closed and no longer requiring continuing review.

The IRB will inform the Principal Investigator (PI) and the PI's department chair in writing about any suspensions or terminations, including detailed reasons for these actions The suspension's terms and conditions must be clearly defined, and the investigator will have the opportunity to respond either in person or in writing.

The IRB Chair, AVP-RC, or IO has the authority to suspend research to protect the rights and welfare of participants Any suspension or IRB approval initiated by these individuals must be reported to a convened IRB meeting for further discussion and action.

Research may only terminated by the convened IRB Terminations of protocols approved under expedited review must be made by the convened IRB

When a study's approval is suspended or terminated by the convened IRB or an authorized individual, it is crucial to take necessary actions to safeguard the rights and welfare of currently and formerly enrolled subjects This includes informing them about the suspension or termination, facilitating safe withdrawal procedures such as transferring subjects to another investigator, arranging for ongoing care or follow-up outside the research, allowing certain research activities to continue under independent monitoring, and ensuring follow-up for safety reasons.

If the convened Institutional Review Board (IRB) or the individual who ordered the suspension or termination deems follow-up with subjects necessary for safety reasons, they will ensure that subjects are informed accordingly Additionally, any adverse events or outcomes must be reported to both the IRB and the sponsor.

The investigator is required to consistently report adverse events and unexpected issues to both the IRB and the sponsor, even during a suspension, ensuring that all events that necessitate reporting throughout the study are also documented during the suspension period.

Refer to Section 11 for the University’s requirements for reporting suspensions or terminations to external agencies

The Institutional Review Board (IRB) is responsible for conducting ongoing reviews of research that falls under the Common Rule, ensuring these reviews occur at suitable intervals based on the research's risk level, but at least annually The scheduled date for each continuing review is documented in the IRB's electronic management system as well as in the approval letters for both initial and continuing reviews.

Unless an IRB determines otherwise, continuing review of research subject to the Common Rule is not required in the following circumstances:

 Research eligible for expedited review in accordance with 45 CFR 46.110;

 Research reviewed by the IRB in accordance with the limited IRB review described in

Recent research has advanced to a stage where it focuses on either data analysis, which includes the examination of identifiable private information or biospecimens, or the retrieval of follow-up clinical data from procedures that participants would naturally undergo as part of their clinical care, all in accordance with an IRB-approved study.

Studies not requiring continuing review must still adhere to prompt reporting requirements for proposed amendments, unanticipated risks, and protocol violations Additionally, a status report must be submitted every two years to provide updates on the research activity Investigators will receive reminder emails for this report, which will be reviewed by ORC staff to ensure compliance with institutional policies, including human subjects training and conflict of interest review Non-compliance with the status report submission may lead to suspension of the study until the issue is resolved, in accordance with SBU’s HRPP policy.

Studies that fall into these categories may be determined to require continuing review For example, the IRB may determine that continuing review is required when:

1 Required by other applicable regulations (e.g., FDA);

2 Required by the terms of a grant, contract, or other agreement

3 The research involves topics, procedures, or data that may be considered sensitive or controversial;

4 The research involves particularly vulnerable subjects or circumstances that increase subjects’ vulnerability;

5 An investigator has minimal experience in research or the research type, topic, or procedures; and/or

6 An investigator has a history of noncompliance

When the Institutional Review Board (IRB) mandates a continuing review for specific research, it will record the rationale in its official documentation and inform the investigator through the IRB determination letter.

Continuing review is a mandatory requirement under FDA regulations, ensuring that the IRB evaluates ongoing FDA-regulated research and other studies requiring such reviews for funding or contractual purposes This review occurs at intervals appropriate to the research's risk level, with a minimum frequency of once per year while the research remains active The IRB will document the due date for continuing reviews in its electronic management system and on both initial and continuing review approval letters.

The Institutional Review Board (IRB) determines the approval period for research protocols during the initial and continuing reviews For studies governed by the Common Rule, the IRB conducts ongoing evaluations at intervals that correspond to the research's risk level, ensuring reviews occur at least annually, unless specified otherwise in the Standard Operating Procedures (SOPs).

The Institutional Review Board (IRB) specifies an approval period with a clear expiration date for both initial and continuing approvals IRB approval lapses at midnight on this expiration date, which is set no later than one year after the last review by the full committee For studies reviewed by the convened IRB, approval starts on the date of the final review, either when the research is approved or when a final reviewer approves it after addressing non-substantive modifications.

Amendment of an Approval Protocol

Investigators are required to obtain IRB approval before making any modifications to their approved research, regardless of the changes' significance The only exception is if a change is essential to eliminate an immediate hazard to a subject, in which case the IRB must be notified without delay.

Modifications to a study may be approved by the IRB if they align with the original authorization For instance, if a researcher intends to include an additional population in an existing study without altering its procedures or objectives, submitting a modification request is typically suitable Similarly, changes to a procedure that do not affect the study's purpose are also considered appropriate for modification.

On March 19, 2020, researchers must maintain the original aims, purpose, and intent of their study when working with human subjects If any changes to these elements are desired, a new application for human subjects approval will be necessary.

Investigators are required to submit all revised documents affected by modifications to the Institutional Review Board (IRB), along with a justification and summary of the changes Whenever feasible, materials should be provided with track changes to clearly highlight the revisions made.

IRB staff will assess if proposed changes qualify for an expedited review process, applicable for minor modifications that do not increase risk, or if they require a full board review In cases of expedited review, the IRB reviewer(s) hold the authority to approve the changes; otherwise, the protocol will be referred to the full board for further evaluation.

3.13.1 Expedited review of Protocol Modifications

The IRB can utilize expedited review processes to assess minor modifications in ongoing research that has already received approval, during the designated approval period This expedited review may be conducted by the IRB Chair or designated members of the IRB.

The reviewer(s) fill out the Amendment Review Sheet for IRB Members to assess if the proposed modifications qualify for expedited review They also evaluate whether the research, with the suggested changes, still adheres to the necessary regulatory approval criteria.

Reviewers will assess whether details about modifications could influence participants' willingness to remain involved in the research, and if so, they will determine whether to disclose that information to the participants.

3.13.2 Full Board Review of Protocol Modifications

When a significant change is proposed in a research study, such as adding procedures that increase risk or discomfort, it must be reviewed and approved by the Institutional Review Board (IRB) at a convened meeting before implementation The sole exception is for changes made to eliminate immediate hazards to research subjects, in which case the IRB should be promptly informed post-implementation and will review the change to ensure the ongoing welfare of the subjects is maintained.

All documents provided by the investigator are accessible to all IRB members

During the meeting, the primary reviewer provides a summary of the proposed changes and guides the Institutional Review Board (IRB) in assessing the regulatory criteria for approval The IRB's role is to evaluate whether the research, with the suggested modifications, still complies with the necessary regulatory standards for approval.

When the Institutional Review Board (IRB) evaluates modifications to previously approved research, it assesses how these changes may impact participants' willingness to continue their involvement If relevant, the IRB determines whether to disclose this information to the subjects.

Closure of Protocols

The conclusion or early termination of a study constitutes a significant activity change that must be reported to the IRB through the electronic management system While participants will no longer be "at risk," submitting a final report to the IRB is essential for closing their files and supplying valuable information for the assessment and approval of related studies.

Reporting IRB Actions

All IRB action letters are typically prepared by IRB staff and made accessible to the Principal Investigator (PI) and research team within ten working days after member review or the IRB meeting for expedited and full review studies, respectively Upon approval, a written notification will be sent along with the approved consent documents, which will include stamped approval and expiration dates While expiration date stamping is not necessary for studies approved under the new Common Rule, the study application must still include this information For required modifications or deferrals, the notification will specify the necessary changes and their rationale In cases of disapproval, termination, or suspension, the notification will outline the reasons for these decisions.

All correspondence between the IRB and investigators are retained in the electronic management system.

Appeal of the IRB Decisions

When a protocol is disapproved, deferred, or requires modifications at an IRB meeting, the IRB will provide the Principal Investigator (PI) with written notification detailing the specific deficiencies and necessary modifications for approval This notification will also include the reasons for the IRB's decision and allow the investigator the opportunity to respond in writing.

When disagreements arise between the Institutional Review Board (IRB) and the Principal Investigator (PI) concerning proposed changes, and informal resolutions fail, either party may appeal to the Institutional Official (IO) for a resolution The IO has the authority to convene a meeting to foster dialogue and facilitate a resolution between the IRB and the PI.

The Investigational Officer (IO) can offer input and suggestions to the Institutional Review Board (IRB) for the swift resolution of issues; however, the ultimate authority for approval lies with the IRB.

Policy

The University is responsible for maintaining comprehensive documentation of the Institutional Review Board's (IRB) activities These records must be readily accessible for inspection and copying by authorized representatives from the FDA, OHRP, sponsors, and other designated entities during reasonable hours and in an appropriate manner.

IRB Records

The IRB records include, but are not limited to:

3 Training records The ORC maintains accurate records listing research investigators, IRB members, and IRB staff that have fulfilled the facility’s human subject training requirements

4 IRB correspondence (other than protocol related)

5 IRB Study Files (See Section 4.3 for information included in study files)

6 Documentation of Emergency Exemption from Prospective IRB Approval (21 CFR

7 Documentation of Exceptions from Informed Consent Requirements for Emergency Use of a Test Article ((21 CFR 50.23)

8 Documentation of exemptions, including when limited IRB review is a condition of exemption

9 Documentation of convened IRB meetings minutes

10 Documentation of review by an external IRB when appropriate

11 Documentation of IRB reliance and cooperative review agreements

For nonexempt research involving human subjects under the Common Rule, or exempt research requiring limited IRB review, institutions must document their reliance on an external IRB for oversight This is essential when the IRB overseeing the research is not operated by the institution itself.

On March 19, 2020, it is essential to establish oversight of research activities and clearly define the responsibilities of each entity involved to ensure compliance with policy requirements This can be achieved through a written agreement between the institution and the Institutional Review Board (IRB), the implementation of a comprehensive institution-wide policy directive that delineates responsibilities between the institution and any unaffiliated IRB, or by outlining these responsibilities within the research protocol itself.

14 Protocol violations submitted to the IRB

16 Documentation of complaints and any related findings and/or resolution.

IRB Study Files

ORC will maintain an electronic study file for each IRB study submission that is submitted via the electronic management system for review

All communications related to the Institutional Review Board (IRB) are systematically preserved, utilizing various methods such as an electronic management system, IRB staff email, or physical documentation The IRB study files encompass a range of materials, ensuring comprehensive record-keeping.

1 Protocol and all other documents submitted as part of a new protocol application

The protocol and all accompanying documents submitted for the ongoing review or termination of a research application must include progress reports, statements of significant new findings shared with subjects, and reports detailing any injuries to patients.

3 Documents submitted and reviewed after the study has been approved, including reports of modifications to research/amendments and adverse event reports

4 Copy of the IRB-approved Consent/permission/assent forms

5 Sponsor-approved (including DHHS) sample consent form document and protocol, when they exist

6 IRB reviewer forms (when expedited review procedures are used)

7 Documentation of type of IRB review

To ensure an expedited review, it is essential to provide documentation of risk determination, the approval period, and any regulatory requirements This includes protocol-specific findings that support decisions related to waivers or alterations of the consent process, as well as research involving vulnerable populations such as pregnant women, fetuses, neonates, prisoners, and children.

9 For expedited review, the rationale for an expedited reviewer’s determination under 45 CFR 46.110(b)(1)(i) that research appearing on the expedited review list described in 45 CFR 46.110(a) is no more than minimal risk

10 Documentation of all IRB review actions, including the rationale for conducting continuing review of research that otherwise would not require continuing review

11 Notification of expiration of IRB approval to the PI and instructions for submitting relevant continuing review materials

12 Notification of suspension of research

14 Copies of approval letters and forms that describe what PI must have before beginning the study

15 IRB correspondence to and from research investigators

16 All other IRB correspondence related to the research

17 Reports of unanticipated problems involving risk to subjects or others and adverse events

18 Documentation of audits, investigations, reports of external site visits

19 Scientific evaluations, if any, beyond the scientific merit attestations provided by departmental chairs/review committees.

IRB Minutes

IRB proceedings must be documented and accessible for review by the next scheduled meeting, with the IRB Chair reviewing them beforehand Once approved, the IRB minutes cannot be modified by any authority without the convened IRB's consent Additionally, the minutes must include enough detail to clearly convey the meeting's outcomes.

Attendance records must include the full names of each member and their representative capacities, such as scientist, non-scientist, or representative of research subjects A roster sheet will accompany the minutes, detailing each IRB member's role It is essential to document members or alternates participating via videoconference or teleconference, confirming they received all relevant materials beforehand and could engage fully in discussions Additionally, the names of any alternates attending in place of absent members should be noted, along with their designated roles Consultants present must be identified, including a brief overview of their expertise and confirmation that they did not participate in voting Finally, the names of non-members and guests, including IRB staff, investigators, and study coordinators, should also be recorded.

Votes on each action will be based on the members present during the voting process Any member who recuses themselves due to a conflict of interest will be named, and the reason for their recusal will be documented.

2 The presence of a quorum throughout the meeting, including the presence of one member whose primary concern is in a non-scientific area

5 Actions taken, including separate deliberations, actions, and votes for each protocol undergoing initial review, continuing review, or review of modifications by the convened the IRB

6 Votes on these actions (total number voting; number voting for; number voting against; number abstaining; number of those recused)

7 Basis or justification for these actions including required changes in research

8 Summary of controverted issues and their resolution

9 Approval period for initial and continuing approved protocols, when applicable, including identification of research that warrants review more often than annually and the basis for that determination

10 The rationale for requiring continuing review of research that otherwise would not require continuing review

11 Risk level of initial and continuing approved protocols

The research must provide protocol-specific documentation demonstrating compliance with the necessary criteria outlined in 45 CFR 46.116(d) when approving a consent procedure that modifies or omits certain elements of informed consent or when waiving the informed consent requirement This documentation can also be found in a supplementary meeting document titled “Final Meeting Determination Supplement: CONSENT.”

WAIVERS”) available with the meeting minutes

The research must adhere to the necessary criteria outlined in 45 CFR 46.117(c) for protocol-specific documentation when consent documentation requirements are waived Alternatively, this documentation can be found in the supporting meeting document titled “Final Meeting Determination Supplement: CONSENT WAIVERS,” which is accessible alongside the meeting minutes.

When reviewing research involving populations protected under Subparts B, C, or D of 45 CFR 46, the IRB must provide documented justifications and findings in the meeting minutes or supporting documents These records include the "Final Meeting Determination Supplement: Minors," ensuring compliance with regulatory requirements.

The Determination Supplement addresses the considerations for pregnant women and prisoners in research studies The Institutional Review Board (IRB) may agree with the justifications provided by the investigator in the submission materials, including any modifications made during the review process.

Certain groups, including individuals with mental disabilities and those who are economically or educationally disadvantaged, require special protections in research settings This is essential to safeguard them from potential coercion or undue influence, irrespective of the research's funding source.

16 The rationale for significant risk/non-significant risk device determinations

17 Determinations of conflict of interest and review of management plans

18 Identification of any research for which there is need for verification from sources other than the investigator that no material changes are made in the research

19 A list of research approved since the last meeting utilizing expedited review procedures, including limited IRB review conducted using expedited procedures

When an IRB member has a conflicting interest regarding the research being reviewed, they must not participate in the deliberations or voting on that proposal, ensuring that the quorum is maintained throughout the process.

21 Key information provided by consultants will be documented in the minutes or in a report provided by the consultant

22 Justification of any deletion or substantive modification of information concerning risks or alternative procedures contained in the DHHS-approved sample consent document.

IRB Membership Roster

A comprehensive membership list of IRB members is essential, detailing each member's identity and their expected contributions to IRB discussions This list should include specific information about each member to ensure clarity regarding their roles and expertise in the deliberative process.

3 Affiliated or non-affiliated status (neither the member nor an immediate family member of the member may be affiliated with the University)

According to the Office for Human Research Protections (OHRP), individuals are classified as scientists or non-scientists based on their training and professional background Scientists are those whose education and occupation lead them to approach scientific activities from a behavioral or biomedical research perspective In contrast, non-scientists are individuals whose training and background orient them to view research activities from outside these scientific disciplines.

5 Indications of experience (specialties, etc.) sufficient to describe each member's chief anticipated contributions to the IRB deliberations

Each Institutional Review Board (IRB) member brings unique representative capacities, including a designated prisoner representative and members with expertise in working with vulnerable populations such as children, pregnant women, and adults with impaired decision-making abilities This diverse knowledge ensures that the IRB effectively addresses the ethical considerations and potential coercion or undue influence that may arise in research involving these sensitive groups at SBU.

7 Role on the IRB (Chair, Co-Chair, etc.)

8 Voting status (Any ex officio members are non-voting members)

9 For alternate members, the primary member for whom the member could substitute

The ORC is responsible for maintaining an up-to-date IRB membership list; however, it is not obligated to report any changes to the roster to the Office for Human Research Protections (OHRP) under the Department of Health and Human Services (DHHS).

Documentation of Exemptions

Documentation of verified exemptions requires the reviewer to cite a specific exemption category and confirm that the investigator's activity meets the criteria outlined in Section 3.5.2 If an exemption involves limited IRB review, the documentation must note this and detail the IRB's actions regarding the research aspects subject to limited review, following the established procedures for expedited or convened board reviews as specified in this policy.

Documentation of Expedited Reviews

IRB records for expedited initial and continuing reviews must confirm that the study meets the criteria for expedited review, specifying the applicable category or exempt status requiring limited IRB review Additionally, documentation must demonstrate that the activity fulfills the approval criteria, include the approval period if relevant, and provide necessary regulatory determinations, along with study-specific findings that justify these decisions.

1 Approving a procedure which waives or alters the informed consent process;

2 Approving a procedure which waives the requirement for documentation of consent;

3 Approving research involving pregnant women, human fetuses, or neonates;

Access to IRB Records

The IRB has policies and procedures to protect the confidentiality of research information:

1 All paper IRB records are kept secure in the ORC, which is closed and locked when unattended

2 The University’s IRB electronic management program, is hosted at a data center facility on the Main Campus Facilities are secure, data is mirrored, and is backed up nightly

Authorized users have limited access to the facility, with state-of-the-art security measures in place User IDs and passwords adhere to widely accepted commercial and federal security standards All web-based transmissions utilize certified SSL (256-bit Secure Socket Layer) encryption Strict permission protocols guarantee that only authorized individuals can access sensitive data.

Access to Institutional Review Board (IRB) records, whether in paper or electronic format, is restricted to specific individuals including the Institutional Official (IO), IRB Chair, IRB members, IRB Administrators, IRB staff, the Assistant Vice President for Research Compliance (AVP-RC), authorized institutional officials, and officials from federal and state regulatory agencies such as the Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA) Accreditation bodies are also granted access and may suggest additional security measures for the protection of IRB records All other requests for access are limited to individuals with a legitimate need, as determined by the AVP-RC or the IO.

4 Records are accessible for inspection and copying by authorized representatives of federal regulatory agencies during regular business hours

5 Paper records may not be removed from the ORC office; however, the IRB staff will provide copies of records for authorized personnel if requested

6 All other access to IRB study files, paper or electronic, is prohibited.

Record Retention

Records pertaining to IRB-approved research must be retained for a defined time period once the research is permanently closed

Research is permanently closed if all of the following conditions are met:

 No new subjects will be enrolled; and

 There are no more interventions or interactions with enrolled subjects; and

No additional analysis of identifiable data or tissue will take place, as all analyses are either complete or the data and tissue have been permanently de-identified, meaning all identifiers and keys to codes have been destroyed.

The time period during which records must be kept once the research is permanently closed depends on the study specifics:

 For records that DO NOT include identifiable health information and are not subject to

FDA regulation, contract or journal requirement: Records relating to the research must be retained for at least 3 years after completion of the research

 For records that are subject to specific contract or journal requirements: Records relating to the research must be retained per the stated contractual or journal obligation

 For records that DO include identifiable health information: Records relating to the research must be retained for at least 7 years after completion of the research

For Investigational New Drug (IND) research, the FDA mandates that sponsors and investigators maintain records and reports for two years following the approval of a marketing application for the drug If the application is not approved, these records must be retained for two years from the date of the application.

D a t e : 3 / 1 9 / 2 0 2 0 years after shipment and delivery of the drug for investigational use is discontinued and the FDA so notified.”

For Investigational Device Exemption (IDE) research, the FDA mandates that investigators or sponsors retain records for a minimum of two years following the later of two key dates: the termination or completion of the investigation, or the date when the records are no longer necessary for supporting a premarket approval application or a notice of completion for a product development protocol.

For research supported by industry or private foundations, investigators are required to retain records for a duration specified by the sponsor or for a minimum of three years, whichever period is longer.

5 Obtaining Informed Consent from Research Subjects

Policy

Researchers affiliated with the University must obtain legally effective informed consent from human subjects or their authorized representatives before involving them in research, unless a waiver has been granted by the IRB as outlined in Section 5.8 Informed consent must be documented using a written consent form that has received IRB approval, as specified in Section 5.6, except in cases detailed in Section 5.12.

The IRB will evaluate both the consent process and the procedures for documenting informed consent to ensure that adequate informed consent is obtained from subjects.

Definitions

A Legally Authorized Representative (LAR) is defined under federal regulations (45 CFR § 46.102(c)) as an individual or entity legally permitted to provide consent on behalf of a potential research participant for their involvement in specific procedures related to the study.

According to New York State's Family Health Care Decisions Act (FHCDA), in the absence of a designated health care agent, the highest-ranking available, willing, and competent individual on the surrogate list is authorized to make health care decisions for a patient who is unable to do so.

1 A court-appointed guardian (per NYS Mental Health Law Article 81);

A health care proxy must be properly executed and signed when the individual has decision-making capacity for it to be effective It designates a representative or agent to make health care decisions on behalf of the subject, reflecting their wishes, if any.

D a t e : 3 / 1 9 / 2 0 2 0 regard to research as expressed in the health care proxy govern (e.g prohibiting all research or permitting only research which may provide a direct benefit);

3 The spouse, if not legally separated from the patient, or the domestic partner;

4 A son or daughter eighteen years of age or older;

6 A brother or sister eighteen years of age or older; or

A close friend is defined as an individual who is at least eighteen years old and has established consistent communication with the subject, allowing them to be well-acquainted with the subject's activities, health, and beliefs.

Legal guardian: A person appointed by a court of appropriate jurisdiction.

General Requirements

Investigators must obtain consent prior to entering a subject into a study and/or conducting any procedures required by the protocol, unless consent is waived by the IRB

The Principal Investigator (PI) must ensure that all team members involved in the consent process are properly trained Those delegated to obtain consent should possess a thorough understanding of the research and the consent procedure, enabling them to effectively answer any questions from potential subjects.

Except as provided elsewhere in these Standard Operating Procedures:

1 Before involving a human subject in research, an investigator shall obtain the legally effective informed consent of the subject or the subject’s LAR

An investigator must obtain informed consent in a manner that allows the prospective subject or their legally authorized representative (LAR) ample opportunity to discuss and reflect on the decision to participate, while also reducing the risk of coercion or undue influence.

3 The information that is given to the subject or the LAR shall be in language understandable to the subject or the LAR

Prospective subjects or their legally authorized representatives (LARs) must receive essential information that a reasonable individual would require to make an informed decision regarding participation Additionally, they should be given the opportunity to discuss this information thoroughly.

Informed consent should start with a clear and concise summary of essential information that helps potential participants or their legally authorized representatives (LARs) understand the reasons for and against participating in the research This information must be organized effectively to enhance comprehension and facilitate informed decision-making.

6 Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists

D a t e : 3 / 1 9 / 2 0 2 0 of isolated facts, but rather facilitates the prospective subject’s or LAR’s understanding of the reasons why one might or might not want to participate

Informed consent must not contain any language that suggests the subject or their legally authorized representative (LAR) is waiving legal rights or releasing the investigator, sponsor, institution, or their agents from liability due to negligence.

The informed consent requirements outlined here do not override any relevant federal, state, or local laws, including those established by the official governing bodies of American Indian or Alaska Native tribes, which may impose additional criteria for informed consent to be legally valid.

Informed Consent Process

Informed consent must be obtained under the following circumstances:

Informed consent can only be acquired from individuals who possess the legal and mental capacity to do so; for those lacking this capacity, consent must be secured from a legal guardian or an authorized representative.

2 The informed consent process shall be sought under circumstances that provide the subject (or legally authorized representative) with sufficient opportunity to consider whether or not to participate

3 The informed consent process shall be sought under circumstances that minimize the possibility of coercion or undue influence

Informed consent information must be conveyed in clear, accessible language that is understandable to the participant or their legally authorized representative It is essential that the language used is suitable for individuals with an education level of at least 8th grade, utilizing layman’s terms to describe the research effectively.

Informed consent for non-English speaking subjects must be obtained in a language they understand, or through their legally authorized representative To comply with this requirement, the Institutional Review Board (IRB) mandates the presence of a qualified interpreter during consent conferences when the prospective subject is not fluent in the language of the person obtaining consent.

 See section 17.8 for additional policy governing inclusion of non-English speakers

The informed consent process must avoid any exculpatory language that could lead participants to waive their legal rights or suggest that investigators, sponsors, or university employees are exempt from liability for negligence.

The Principal Investigator (PI) can delegate the task of obtaining consent from research subjects to team members; however, the PI remains ultimately responsible for ensuring that each prospective subject is thoroughly informed about all aspects of the research.

D a t e : 3 / 1 9 / 2 0 2 0 understands the information provided It is the PI's responsibility to train and supervise the study personnel who are obtaining consent

The individual designated as the 'person obtaining consent' is crucial in guiding the potential subject through the consent process, which involves discussing all study aspects outlined in the consent form and thoroughly reviewing it while addressing any questions This person must assess the potential subject's understanding by asking relevant questions and ensuring they comprehend the implications of their participation Importantly, the potential subject should feel free to make an uninfluenced decision regarding their involvement in the study The consent process extends beyond the signing of the document, as the person obtaining consent is responsible for continually evaluating the subject's understanding and willingness to participate, as well as providing any new information that may impact their decision.

Determining a potential adult subject's ability to consent to research

For the purpose of this section, a subject has the capacity to consent to his or her own participation in a research activity if s/he demonstrates the following:

1 That the activity is research, not standard treatment;

2 The risks and benefits of a study;

3 The alternatives that are available if s/he does not participate; and

4 The decision not to participate will be accepted without penalty, i.e without jeopardizing clinical care

When deciding on participation, it is crucial for potential subjects to demonstrate the ability to rationally evaluate information This includes understanding the unique risks, benefits, and alternatives that pertain to their individual circumstances For instance, a person with severe depression may recognize these factors but may lack the motivation to care about them or may even desire to take risks Consequently, individuals in such situations should not be deemed capable of providing informed consent.

See Section 6.9 for further discussion regarding adults who cannot consent for themselves

Basic Elements of Informed Consent

This study entails comprehensive research aimed at understanding specific objectives, with participants expected to engage for a defined duration It includes a detailed outline of the procedures involved, highlighting any experimental methods utilized Additionally, the study provides a clear description of potential risks or discomforts that participants may encounter during their involvement.

2 A description of any benefits to the subject or to others which may reasonably be expected from the research;

3 A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

4 A statement describing the extent, if any, to which confidentiality of records identifying the subject must be maintained;

For research that poses more than minimal risk, it is essential to provide a clear explanation regarding the availability of medical treatment for any research-related injuries This includes details on who will be responsible for covering the costs of such treatment and whether additional financial compensation is offered, as outlined in section 17.6 of the SBU policy on industry-funded clinical trials.

For any inquiries regarding the research or to express concerns and complaints, please reach out to the designated member of the research team In the event of a research-related injury, contact the appropriate personnel immediately for assistance.

For inquiries regarding the research, concerns or complaints, and questions about participants' rights, individuals can contact the Institutional Review Board (IRB) This contact information is essential if research staff are unavailable or if subjects prefer to discuss matters with someone outside the research team.

Participation in this study is entirely voluntary, and individuals may decline to take part without facing any penalties or losing any benefits they are entitled to Participants also have the right to withdraw from the study at any time, ensuring that their benefits remain intact regardless of their decision.

When conducting research that involves identifiable private information or biospecimens, it is essential to include a clear statement regarding the potential use of this data Researchers must inform participants that identifiers may be removed, allowing the information or biospecimens to be utilized in future studies or shared with other investigators without requiring additional consent Alternatively, researchers may clarify that even with identifiers removed, the collected data will not be used or shared for future research purposes.

For FDA-regulated studies, add the possibility that the Food and Drug Administration may inspect the records needs to be included in the statement regarding subject confidentiality

For applicable clinical trials (see Section 17.4), the following statement must be included verbatim:

A detailed description of this clinical trial will be accessible at http://www.ClinicalTrials.gov, in accordance with U.S law The website will maintain your privacy by excluding any identifying information, and will primarily feature a summary of the trial results You can visit this site anytime for updates and information.

Additional elements of informed consent to be applied, as appropriate:

The treatment or procedure being considered may carry risks that are currently unknown, particularly when it involves investigational test articles or other procedures where the potential dangers to subjects are not well understood.

Pregnant women or those of childbearing potential should be aware that certain treatments or procedures may pose unforeseen risks to the embryo or fetus This is particularly relevant in research contexts where the effects of drugs, devices, or other interventions on fetal health are not yet fully understood.

The investigator may terminate a subject's participation in the study without their consent under specific anticipated circumstances, such as if the subject experiences adverse health effects, fails to adhere to study protocols, or if the study is deemed unsafe or unethical.

4 Any additional costs to the subject that may result from participation in the research (e.g include when it is anticipated that subjects may have additional costs)

5 The consequences of a subject’s decision to withdraw from the research (e.g include when withdrawal from the research is associated with adverse consequences)

6 Procedures for orderly termination of participation by the subject (e.g include when the protocol describes such procedures)

Participants will be informed of any significant new findings that arise during the research, particularly those that may influence their willingness to continue in the study This is especially important for long-term research where interim information is likely to emerge throughout the process.

8 The approximate number of subjects involved in the study (e.g include when the research involves more than minimal risk)

9 A statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit;

10 A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions;

When conducting research involving biospecimens, it is essential to identify whether the study will include whole genome sequencing, which entails sequencing a human germline or somatic specimen to generate the genome or exome sequence.

Documentation of Informed Consent

Except as provided in Section 5.12 of this document, informed consent must be documented by the use of a written consent form approved by the IRB

Informed consent is obtained through a written consent form, which must be approved by the Institutional Review Board (IRB) and signed by the subject or their legally authorized representative If the consent form is translated into a foreign language, an affidavit confirming the accuracy of the translation from an IRB-approved English version must be provided by an independent translator Both the translated form and the affidavit require IRB approval prior to use The person obtaining consent from non-English speaking subjects should be a fluent investigator or work with a qualified interpreter For further guidelines on including non-English speakers, refer to section 17.8.

2 For research conducted in accordance with ICH-GCP E6 or in facilities subject to Joint

Commission requirements, the name of the person who obtained consent and the date they did so is documented on the written consent form;

A signed and dated consent form must be provided to the individual who signed it, while the investigator retains the original in the research records Additionally, when applicable, a copy of the consent form should be uploaded into the electronic health record.

4 Documentation of consent must be either via:

A written consent document must include essential elements of informed consent The investigator should ensure that the subject or their legally authorized representative has sufficient time to read the informed consent form prior to signing Alternatively, the form can be read aloud to the subject or their representative to ensure understanding.

A brief written consent document confirms that the essential elements of informed consent were communicated orally to the participant or their legally authorized representative Key information was prioritized and presented to the subject before any additional details were shared This approach ensures clarity and understanding in the consent process.

 There must be a witness to the oral presentation; and

 The IRB must approve a written summary of what is to be signed by the subject or representative; and

 The witness must sign both the short form and a copy of the summary; and

 The person actually obtaining consent must sign a copy of the summary; and

 A copy of the summary must be given to the subject or representative, in addition to a copy of the short form

When this 'short form' procedure is used with subjects who do not speak English:

 The oral presentation and the short form written document should be in a language understandable to the subject;

 The IRB approved English language informed consent document may serve as the summary; and

A witness involved in the consent process must be proficient in both English and the subject's language If an interpreter aids in obtaining consent, they can act as the witness, provided they have no ties to the study Additionally, all foreign language versions of the short form document, along with a translator affidavit, must be submitted to and approved by the IRB before use.

Upon consenting to participate in the study, subjects will receive an English summary and a short form Additionally, they must be provided with a translated summary in their native language promptly after their enrollment in the study.

English and Spanish versions of an IRB-approved 'short form' document can be found in the Forms Library of the electronic management system Expedited review is permissible for these versions if the protocol, full English informed consent document, and English short form document have received prior approval from the convened IRB For further details on policies regarding non-English speakers, refer to section 17.8.

Special Consent Circumstances

See section 17.8 for SBU policy on non-English speaking subjects

The IRB may approve a Braille consent document for blind participants, ensuring its accuracy through a printed transcription or review by a Braille reader If feasible, participants will sign the Braille consent; if not, verbal consent will be obtained, witnessed, and documented as outlined in section 5.8.4.

5.8.3 Consenting in American Sign Language (ASL)

For deaf individuals proficient in American Sign Language (ASL), the Institutional Review Board (IRB) can authorize a consent process that incorporates ASL alongside an IRB-approved written consent form When this method is approved, a designated person must utilize a qualified ASL interpreter to facilitate the consent process, ensuring that all documentation adheres to the stipulations outlined in section 5.7.

In cases where participants cannot read a written consent form, such as individuals who are blind or illiterate, the Institutional Review Board (IRB) may authorize a verbal consent process This is contingent upon the participant's ability to comprehend the study's concepts and assess the associated risks and benefits when explained verbally, as well as their capacity to express their consent or refusal to participate in the study.

The consent process requires that the consent form be read to participants, allowing them the opportunity to ask questions An IRB-approved audiotape may be utilized during this process Participants capable of doing so will sign or mark an X on the consent form, while others may provide verbal consent Both the individual obtaining consent and a witness must sign the written consent form, noting that an oral process was employed and documenting any verbal consent given This consent procedure will also be recorded in the medical records or according to institutional policy Participants receive signed copies of the consent form, and when feasible, these documents may be provided in audio or video format.

For research that is no more than minimal risk, documentation of consent may be waived if the criteria at Section 5.12 are met.

Consent Monitoring

The Institutional Review Board (IRB) is empowered by 45 CFR 46.109(e) and 21 CFR 56.109(f) to implement specialized monitoring of the informed consent process in human research studies, ensuring the protection of participants' rights and welfare.

The Office of Research Compliance informs Principal Investigators (PIs) through the IRB approval letter to reach out when the first subject is set for consent as part of the regular QA assessment program If possible, an ORC staff member will observe the consent process to ensure compliance and quality.

 Assure that the research teams satisfy all federal, state and institutional requirements for obtaining consent from research participants;

 Assure that an appropriate consent process is followed, appropriately completed and documented;

 Assure the approved consent process is being followed;

 Assure the information provided to the participant was accurate and conveyed in understandable language;

 Assure the participant had sufficient time to consider study participation;

 Assure the possibility of coercion and undue influence are not evident;

 Ensure that subjects are truly giving Informed Consent; and

 Assure the subject appeared to understand the information and gave their voluntary

The consent monitoring process can also be done via general, random not-for-cause reasons, or it may be determined by the IRB that such consent monitoring is warranted

The factors that the IRB may consider in making the determination that special monitoring of the consent process may include, e.g.:

 Studies that involve complex and complicated procedures or interventions;

 Studies involving Vulnerable Populations (e.g., children, adults unable to consent for themselves);

 Studies involving study staff with minimal experience in administering consent to study participants;

 Concerns raised about study team performance, such as prior findings of noncompliance related to the consent process;

 Presence of study team conflicts of interest;

 Prior complaints about the consent process

Consent monitoring can be carried out by IRB staff, IRB members, or an appointed party designated by the IRB Chair The Principal Investigator (PI) will be informed about the upcoming consent monitoring process, and arrangements will be coordinated with the PI for overseeing the consent procedures.

After monitoring, a report detailing the findings will be submitted to the IRB and included in the meeting minutes The Board will then decide on appropriate actions based on the report, such as initiating non-compliance procedures The Principal Investigator (PI) will receive an email notification regarding the monitoring outcome and any subsequent IRB determinations.

Subject Withdrawal or Termination

Participants in research studies may choose to withdraw for various reasons, or investigators may terminate a participant's involvement regardless of their desire to continue This situation often leads to questions regarding the implications and processes surrounding withdrawal from research participation.

1 Whether the investigator may use, study, or analyze already collected data about the subject who withdraws from the research or whose participation is terminated by the investigator; and

Investigators should anticipate the potential withdrawal of subjects from research and must develop a strategy for continuing to gather data under specific circumstances This article explores the conditions under which data collection can persist and addresses related inquiries.

D a t e : 3 / 1 9 / 2 0 2 0 discussion of what withdrawal will mean and how it will be handled in their research protocols and informed consent documents

Regulatory requirements regarding the retention and use of data after subject withdrawal or termination differ depending on whether or not the research is subject to FDA regulations

When seeking informed consent from subjects, the following information regarding data retention and use must be included:

In FDA-regulated clinical trials, if a participant withdraws from the study, their data up to that point remains in the study database and cannot be deleted The consent form must not provide the option for participants to request the removal of their data.

In research not governed by FDA regulations, investigators must inform participants about their intentions regarding data handling Specifically, they should clarify whether they plan to retain and analyze data collected up to the point of a participant's withdrawal or if they will comply with a participant's request to destroy their data or exclude it from any analysis.

In certain cases, a participant may choose to withdraw from the main interventional aspect of a study while still permitting the investigator to proceed with other research activities outlined in the IRB-approved protocol and informed consent document that require their involvement.

 Obtaining data about the subject through interaction with the subject (e.g., through follow- up interviews, physical exams, blood tests, or radiographic imaging); or

 Obtaining identifiable private information from the subject’s medical, educational, or social services agency records or from the subject’s healthcare providers, teachers, or social worker

When a participant withdraws from the primary interventional component of a research study, other previously consented activities may still proceed Investigators should inquire if the participant is willing to provide ongoing follow-up and data collection after their withdrawal It’s essential to clarify the difference between study-related interventions and the continued follow-up of clinical outcomes, including noninvasive chart reviews of medical data Additionally, discussions must emphasize the importance of maintaining the participant's privacy and confidentiality throughout the process.

If a subject withdraws from the interventional portion of the study, but agrees to continued follow-up of associated clinical outcome information as described in the previous paragraph,

On March 19, 2020, investigators are required to obtain informed consent from participants for their limited involvement in the study, particularly if this was not specified in the original consent form Additionally, Institutional Review Board (IRB) approval for the informed consent documents is necessary.

If a participant withdraws from a study's intervention, does not consent to ongoing follow-up for clinical outcomes, and does not ask for their data to be removed, the investigator is prohibited from accessing the participant's medical or confidential records without consent However, the investigator is allowed to review any study data collected before the withdrawal and may consult public records to verify survival status.

Waiver or Alteration of Informed Consent

An IRB may waive the requirement to obtain informed consent, provided the IRB finds and documents that the below criteria are satisfied

An Institutional Review Board (IRB) can approve a consent process that modifies or omits certain basic and additional elements of informed consent, known as an "alteration," as long as the IRB determines and documents that specific criteria are met.

1 The research or clinical investigation involves no more than minimal risk to the subjects;

2 The research or clinical investigation could not practicably be carried out without the requested waiver or alteration;

Research that utilizes identifiable private information or biospecimens must do so in a manner that is essential for the feasibility of the study This requirement highlights the importance of using identifiable formats, as it may not be possible to conduct the research effectively without this specific data Notably, this criterion is not addressed in the regulations set forth by the FDA or the Department of Justice/National Institute of Justice.

4 The waiver or alteration will not adversely affect the rights and welfare of the subjects; and

5 Whenever appropriate, the subjects or LARs will be provided with additional pertinent information after participation

These criteria may be applied to research subject to FDA regulation as well (although criterion

#3 is not required for an FDA determination)

Waivers/Alterations of consent in research Involving public benefit and services programs conducted by or subject to the approval of state or local officials

An Institutional Review Board (IRB) can waive the informed consent requirement if it determines and documents that specific criteria are met Additionally, the IRB has the authority to approve a consent process that modifies or omits certain basic and additional elements of informed consent.

D a t e : 3 / 1 9 / 2 0 2 0 informed consent (an “alteration”), provided that the IRB finds and documents that the below criteria are satisfied

The research project aims to study and evaluate public benefit or service programs, focusing on procedures for obtaining these benefits, potential changes or alternatives to the programs, and adjustments in payment methods or levels for the services provided This initiative is subject to the approval of state or local government officials.

2 The research could not practicably be carried out without the waiver or alteration

This option does NOT apply to FDA-regulated research

Screening, recruiting, or determining eligibility

An Institutional Review Board (IRB) can approve a research proposal that involves collecting information or biospecimens for screening, recruiting, or assessing the eligibility of potential subjects without obtaining informed consent, provided that specific conditions are satisfied.

1 The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, or

2 The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens

The FDA does not classify records review or oral communication with a subject before obtaining consent as part of the clinical investigation Consequently, consent for these preliminary activities is not necessary, and waivers are not required.

Waiver of Documentation of Informed Consent

The IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds any of the following:

1 Only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality; or

When conducting research involving subjects, particularly in sensitive areas such as domestic violence, it is crucial to ask participants if they wish to receive documentation that connects them to the study Their preferences should take precedence, especially considering the potential risks, such as the possibility of an abuser discovering their communication with investigators.

To waive the requirement for written consent documentation, the Institutional Review Board (IRB) must confirm that the research is not regulated by the FDA, provided that the consent document is the sole link between the subject and the study.

2 The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context

When conducting research involving subjects or legally authorized representatives (LARs) from distinct cultural groups where signing forms is uncommon, it is essential to ensure that the research poses minimal risk of harm In such cases, an appropriate alternative method for documenting informed consent must be implemented However, this option is not applicable for research regulated by the FDA.

When documentation requirements are waived, the IRB mandates that investigators include a written summary in their application detailing the information to be shared with research subjects Additionally, the IRB will evaluate the necessity of providing subjects with a written statement about the research.

Investigators must conduct an appropriate consent process even if they receive approval for a waiver of documentation of consent, unless the Institutional Review Board (IRB) has granted a full waiver of the informed consent requirement.

Waiver of Informed Consent for Planned Emergency Research

In accordance with 21 CFR 50.24, the IRB will consider for review and approval planned research involving life-threatening emergencies where a waiver is proposed for requirement to obtain prospective informed consent

Research conducted in life-threatening emergencies, where obtaining informed consent is waived by the IRB, is governed by 21 CFR §50.24 for FDA-regulated studies and the HHS waiver at 61 FR 51531-33 for non-FDA research Such studies must adhere to an approved IND or IDE, receive prior IRB approval, and be publicly disclosed in the relevant community Notably, this waiver does not apply to research involving children, fetuses, pregnant women, human in vitro fertilization, or prisoners.

Research that proceeds according to this pathway is subject to prospective IRB approval, as opposed to Emergency Use research approved pursuant to 21 CFR §56.104(c)

Under FDA regulations 21 CFR 50.24, an exception to informed consent requirements allows for emergency research when human subjects require urgent medical intervention and are unable to provide informed consent This provision is crucial when the timing of the intervention makes it impractical to obtain consent from legally authorized representatives (LARs).

The Secretary of Health and Human Services (HHS) has established an Emergency Research Consent Waiver under 45 CFR 46.101(i), aligning closely with FDA provisions, except for the IND/IDE requirement Notably, the definition of family members includes spouses of siblings However, this waiver does not extend to research involving prisoners, as specified in 45 CFR.

An exception from consent in emergency medicine research supported by the DoD is prohibited unless a waiver is obtained from the Secretary of Defense

Planned emergency research typically utilizes an FDA-regulated test article, making it subject to strict FDA regulations Principal Investigators (PIs) are advised by the Institutional Review Board (IRB) to reach out to the Office of Research Compliance (ORC) for guidance at least 4-5 months before the intended start date The regulatory requirements are intricate and necessitate consultations with the University, the local community where the research will occur, and the FDA.

Department of Health and Human Services (DHHS)

These Emergency Research policies and procedures apply to Planned Emergency

Research Planned Emergency Research is different from Emergency Use of a Test Article as regulated under FDA 21 CFR 56.104(c)

Planned Emergency Research involves individuals in life-threatening situations who are unable to provide informed consent due to their condition, such as unconsciousness In these cases, timely intervention is crucial and must occur before it is feasible to obtain consent from the subject's legally authorized representative.

The IRB committee responsible for the initial review and approval of emergency research may authorize the study to proceed without obtaining informed consent from all participants beforehand, provided that the IRB includes a licensed physician who is not involved in the clinical trial and determines that specific criteria established by the FDA are met.

In life-threatening situations where available treatments are either unproven or inadequate, it is essential to gather valid scientific evidence to assess the safety and effectiveness of specific interventions This may involve conducting randomized placebo-controlled trials to ensure reliable results.

Obtaining informed consent poses significant challenges due to several factors: a) Subjects may be unable to provide informed consent due to their medical conditions; b) The necessary intervention must be given before it is possible to obtain consent from the subjects' legally authorized representatives; and c) There is no practical method for identifying individuals who are likely to become eligible for participation in the clinical investigation in advance.

Participation in the research offers potential direct benefits to subjects facing life-threatening situations requiring intervention Prior appropriate animal and preclinical studies have been conducted, providing evidence that supports the likelihood of the intervention benefiting individual subjects Additionally, the associated risks of the investigation are deemed reasonable when compared to the known medical conditions of the potential subjects, the risks and benefits of standard therapies, and the information available regarding the proposed intervention's risks and benefits.

4 The clinical investigation could not practicably be carried out without the waiver

The investigational plan outlines the duration of the potential therapeutic window based on scientific evidence, ensuring that the investigator will strive to reach out to a legally authorized representative for each subject within this timeframe If feasible, the investigator will seek consent from the contacted representative instead of proceeding without it Additionally, the investigator will document their efforts to contact these representatives and provide this summary to the Institutional Review Board (IRB) during the continuing review process.

The Institutional Review Board (IRB) has approved informed consent procedures and documentation in accordance with 21 CFR 50.25, which are to be utilized with participants or their legally authorized representatives when feasible Additionally, the IRB has sanctioned the protocols for addressing family members' objections regarding a subject's involvement in the clinical investigation, aligning with paragraph 7(e) of the relevant regulations.

To ensure the rights and welfare of participants in clinical investigations, additional protections will be implemented This includes consulting with representatives from the communities where the research will take place and from which the subjects will be selected, with the involvement of the Institutional Review Board (IRB) when appropriate.

On March 19, 2020, it is essential to ensure public disclosure regarding clinical investigations before they begin, informing communities about the study's plans, risks, and expected benefits Following the completion of the investigation, sufficient information must be shared to update both the community and investigators on the study's demographics and results An independent data monitoring committee should be established to oversee the investigation In cases where obtaining informed consent is not feasible and a legally authorized representative is unavailable, investigators must attempt to contact a family member within the therapeutic window to seek their opinion on the subject's participation These efforts to reach family members should be documented and provided to the Institutional Review Board (IRB) during ongoing reviews.

The Institutional Review Board (IRB) is tasked with ensuring that participants, or their legally authorized representatives, are promptly informed about their inclusion in clinical investigations, along with relevant details and information from the informed consent document Additionally, the IRB must establish procedures to notify participants or their representatives that they can withdraw from the study at any time without facing penalties or losing entitled benefits In cases where a representative is informed and the subject's condition improves, the subject should be updated as soon as possible If a subject enrolled with waived consent passes away before a representative can be contacted, the IRB is responsible for providing information about the clinical investigation to the subject's representative or family member, if feasible.

The Institutional Review Board (IRB) must retain the determinations and documentation specified in this section for a minimum of three years following the completion of the clinical investigation These records must be available for inspection and copying by the FDA, in compliance with 21 CFR 56.115(b).

Posting of Clinical Trial Consent Forms

Each clinical trial funded or supported by a Federal department or agency is required to have one IRB-approved informed consent form posted on a publicly accessible Federal website, such as clinicaltrials.gov This site will serve as a repository for these informed consent forms to ensure transparency and accessibility for enrolled subjects.

If a Federal department or agency involved in a clinical trial decides that specific information, such as confidential commercial data, should remain private, it has the authority to allow or mandate redactions of that information before it is published on a Federal website.

After the clinical trial has closed to recruitment, the informed consent form must be published on the Federal website within 60 days following the last study visit of any participant, in accordance with the protocol requirements.

Policy

Research involving vulnerable subjects at the University requires enhanced safeguards to protect their rights and welfare, particularly when there is a risk of coercion or diminished decision-making capacity The Institutional Review Board (IRB) is responsible for ensuring compliance with all regulatory requirements and implementing necessary additional protections for these individuals.

The following procedures describe the requirements for involving vulnerable subjects in research under the auspices of the University.

Definitions

Children are defined as individuals who have not reached the legal age for consenting to treatments or procedures involved in research, as per the applicable laws of the jurisdiction where the research is conducted In accordance with New York State Law, the Institutional Review Board (IRB) typically considers children to be persons under the age of eighteen For the purposes of these Standard Operating Procedures (SOPs), both "children" and "minors" refer to individuals under eighteen years old, as outlined in New York State Public Health Law, section 2504.

D a t e : 3 / 1 9 / 2 0 2 0 consent (to medical care in general, but NY state law does not specifically reference who may consent to participation in research) as follows:

Individuals aged 18 and older, as well as parents of minors or married individuals, can provide valid consent for their own medical, dental, and hospital services without needing approval from anyone else.

2 Any person who has been married or who has borne a child may give effective consent for medical, dental health and hospital services for his or her child

3 Any person who is pregnant may give effective consent for medical, dental health and hospital services related to the pregnancy

Although consent from 'emancipated' individuals is not typically standard, specific statutory provisions exist for minors in military service or those seeking treatment for AIDS and other sexually transmitted diseases, as outlined in PHL '2781' and PHL '2305'.

In New York State, minors are generally presumed to be unemancipated, placing the burden of proof on those claiming otherwise The law does not explicitly address the consent of children who have reached the age of majority.

"emancipation" with respect to research, the IRB will review issues of consent related to enrollment of these minor children in research on a case-by-case basis

In New York, the authority of a guardian is defined by the court-appointed guardian powers, which specify the scope and duration outlined in the guardian documents These powers can range from limited responsibilities, such as managing financial matters, to more extensive authority Before relying on a guardian's consent for any specific issue, it is essential to send a copy of the legal guardian papers to the Office of Research Compliance (ORC) The ORC, in consultation with the Counsel's office, will evaluate whether the guardian's powers include the authority to consent to research Failing to obtain ORC approval prior to seeking guardian consent is considered a violation of standard operating procedures (SOPs).

Delivery: complete separation of the fetus from the woman by expulsion, extraction, or any other means

Fetus: product of conception from the time of implantation until delivery

Viable fetus: now termed a “viable neonate.”

A nonviable fetus refers to a fetus that, although alive outside the womb, cannot survive independently due to an inability to sustain heart and respiratory functions This definition aligns with the criteria outlined in 45 CFR 46 Subpart B, which also characterizes a non-viable neonate.

Dead fetus: a fetus, which exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord if still, attached

In vitro fertilization: any fertilization either of human ova, which occurs outside the body of a female, through a mixture of donor human sperm and ova or by any other means

Under federal regulations (45 CFR § 46.102(c)), a legally recognized individual or entity has the authority to provide consent on behalf of a potential participant in research activities.

According to the Family Health Care Decisions Act (FHCDA) in New York State, when a patient is incapable of making health care decisions and lacks a designated health care agent, the highest-ranking available, willing, and competent individual from the surrogate list is authorized to make decisions on their behalf.

1 A court-appointed guardian (per NYS Mental Health Law Article 81);

A health care proxy must be properly executed and signed while the individual has decision-making capacity to be effective The wishes of the individual regarding research, as stated in the health care proxy, take precedence, allowing for either a complete prohibition of research or permission for research that offers direct benefits.

3 The spouse, if not legally separated from the patient, or the domestic partner;

4 A son or daughter eighteen years of age or older;

6 A brother or sister eighteen years of age or older; or

A close friend is defined as an individual who is at least eighteen years old and has maintained consistent contact with the subject, allowing them to be well-acquainted with the subject's activities, health, and beliefs.

Viable neonate: being able, after delivery, to survive to the point of being independently maintaining heart and respiration (given the benefit of available medical therapy)

Non-viable neonate: same as a non-viable fetus

Pregnancy is defined as the duration from the confirmation of implantation, which can be indicated by signs such as missed periods or through a medically recognized pregnancy test, until the fetus is either expelled or extracted.

A prisoner is defined as any person who is involuntarily confined in a penal institution This definition includes individuals sentenced under criminal or civil laws, those held in alternative facilities due to specific statutes, and individuals awaiting arraignment, trial, or sentencing.

Surrogate Consent: obtained from a legally authorized representative on behalf of a subject determined to lack decision-making capacity.

Involvement of Vulnerable Populations

When conducting research involving vulnerable populations, such as children, pregnant women, prisoners, and individuals unable to consent, it is essential for the Institutional Review Board (IRB) to implement additional safeguards These measures are crucial to ensure the protection of the rights and welfare of subjects who may be at risk of coercion or undue influence.

When the Institutional Review Board (IRB) evaluates research involving vulnerable subjects at risk of coercion or undue influence, it ensures that the review process includes individuals with expertise in these populations This includes professionals knowledgeable about or experienced in working with children, prisoners, or adults with limited decision-making capacity, thereby enhancing the ethical oversight of studies involving these groups.

FWA and the 45 CFR 46 Subparts

45 CFR 46 has additional subparts designed to provide extra protections for vulnerable populations that also have additional requirements for the IRB

Subpart B - Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research

Subpart C - Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects

Subpart D - Additional Protections for Children Involved as Subjects in Research

Procedures

Initial Review of Research Proposal:

1 The PI should identify the vulnerable subjects to be enrolled in the proposed research at initial review and provide the justification for their inclusion in the study

The IRB assesses the consent strategy for specific vulnerable populations involved in the research In cases where adults are unable to provide consent, the IRB reviews the plan for obtaining permission from legally authorized representatives.

3 The IRB evaluates and approves the proposed plan for the assent of subjects, if applicable

4 The IRB evaluates the research to determine the need for additional protections

5 The IRB assesses the adequacy of additional protections for vulnerable populations provided by the PI

Continuing Review and Monitoring At continuing review, the PI should identify the number of vulnerable subjects enrolled and any that needed an independent monitor in the progress report.

Research Involving Pregnant Women, Human Fetuses and Neonates

The following applies to all research regardless of funding source Since, according to the

University FWA, Subpart B of 45 CFR 46 applies only to DHHS funded research, the funding- source specific requirements are noted in the appropriate sections

6.6.1 Research Involving Pregnant Women or Fetuses

6.6.1.1 Research Not Funded by DHHS

Where the risk to the fetus is no more than minimal, no additional safeguards are required and there are no restrictions on the involvement of pregnant women in research

Where the risk to the fetus is more than minimal, pregnant women or fetuses may be involved in research if all of the following conditions are met:

Pre-clinical studies, including research on pregnant animals, alongside clinical studies involving non-pregnant women, have been conducted where scientifically appropriate These studies provide essential data for evaluating potential risks to pregnant women and their fetuses.

2 The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus;

3 Any risk is the least possible for achieving the objectives of the research;

If research offers potential direct benefits to both the pregnant woman and her fetus, informed consent must be obtained from the pregnant woman in accordance with established guidelines.

If research offers direct benefits exclusively to the fetus, informed consent must be obtained from both the pregnant woman and the father However, the father's consent is not required if he is unavailable, incompetent, temporarily incapacitated, or if the pregnancy is a result of rape or incest.

6 Each individual providing consent under paragraph 4 or 5 of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;

7 For children who are pregnant, assent and permission are obtained in accord with the provisions of permission and assent;

8 No inducements, monetary or otherwise, will be offered to terminate a pregnancy;

9 Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and

10 Individuals engaged in the research will have no part in determining the viability of a neonate

For research funded by the Department of Health and Human Services (DHHS), 45 CFR Subpart B governs the inclusion of pregnant women and fetuses This regulation allows their participation in research only if specific conditions are satisfied, ensuring ethical standards and protections for vulnerable populations.

Pre-clinical and clinical studies, including research on pregnant animals and non-pregnant women, have been conducted to gather data for evaluating potential risks to pregnant women and their fetuses.

The risk to the fetus arises only from interventions or procedures that offer potential direct benefits to the woman or fetus If no such benefits are anticipated, the risk to the fetus must remain minimal, and the research should aim to generate crucial biomedical knowledge that cannot be achieved through alternative methods.

3 Any risk is the least possible for achieving the objectives of the research;

When research offers potential direct benefits to a pregnant woman and her fetus, or when it poses minimal risk to both without any expected benefits, informed consent from the pregnant woman is required This is essential for studies aimed at advancing crucial biomedical knowledge that cannot be acquired through alternative methods.

When research offers direct benefits exclusively to the fetus, informed consent must be obtained from the pregnant woman and the father However, the father's consent is not required if he is unavailable, incompetent, temporarily incapacitated, or if the pregnancy is a result of rape or incest.

6 Each individual providing consent under paragraph 4 or 5 of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;

7 For children who are pregnant, assent and permission are obtained in accord with the provisions of permission and assent in Section 6.8.2;

8 No inducements, monetary or otherwise, will be offered to terminate a pregnancy;

9 Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and

10 Individuals engaged in the research will have no part in determining the viability of a neonate

6.6.2 Research Involving Neonates of Uncertain Viability, and Nonviable Neonates

Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:

1 Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates;

2 Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate;

3 Individuals engaged in the research will have no part in determining the viability of a neonate; and

4 The requirements of Neonates of Uncertain Viability or Nonviable Neonates (see below in this section) have been met as applicable

Neonates of uncertain viability cannot be included in research under this subpart until their viability status is determined Specific additional conditions must be met before involving these neonates in any research activities.

The research aims to significantly improve the survival chances of neonates, focusing on achieving viability while minimizing associated risks.

The research aims to advance crucial biomedical knowledge that cannot be acquired through alternative methods, ensuring that there is no additional risk to the neonate involved in the study.

Informed consent for medical procedures involving a neonate must be obtained from either parent, or if they are unavailable or incapacitated, from a legally authorized representative However, if the pregnancy is a result of rape or incest, the father's consent or that of his representative is not required.

Nonviable Neonates After delivery, nonviable neonates may not be involved in research covered by this subpart unless all of the following additional conditions are met:

1 Vital functions of the neonate will not be artificially maintained;

2 The research will not terminate the heartbeat or respiration of the neonate;

3 There will be no added risk to the neonate resulting from the research;

4 The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and

Informed consent from both parents of a neonate is required, adhering to the established guidelines for permission and assent However, if one parent is unavailable, incompetent, or temporarily incapacitated, the consent of the other parent is sufficient for nonviable neonates Additionally, if the pregnancy resulted from rape or incest, the father's consent is not necessary It is important to note that consent from a legally authorized representative of either parent does not fulfill the requirements outlined in this context.

Viable neonates, defined as those determined to be capable of surviving after delivery, may be included in research studies, provided that such inclusion adheres to the guidelines established by the IRB Review Process and complies with regulations concerning research involving children.

6.6.3 Research Involving, After Delivery, the Placenta, the Dead Fetus or Fetal Material

Research on the placenta, deceased fetuses, macerated fetal material, or tissues and organs obtained from a deceased fetus must comply with all relevant federal, state, and local laws and regulations governing these activities.

Research Involving Prisoners

Prisoners are classified as a vulnerable group in research, prompting the establishment of special protections to prevent exploitation Historically, they were seen as an ideal research demographic due to their confinement in a single location, large numbers, and stable routines However, these same factors that make them convenient for research also heighten the risk of their exploitation.

The concern Subpart C and this policy based on Subpart C attempts to address is whether prisoners have any real choice in participation in research, or whether incarceration prohibits free choice

The following applies to all research involving prisoners, regardless of funding source The requirements in this section are consistent with Subpart C of 45 CFR 46, which applies to DHHS funded research

Research sponsored by the Department of Defense (DoD) strictly prohibits involvement with prisoners of war (POW), which encompasses any individuals captured, detained, or under the control of DoD personnel, including military, civilian, or contractor employees.

This policy governs all biomedical and behavioral research at the University that includes prisoners as subjects While the Institutional Review Board (IRB) may sanction research protocols involving prisoners, investigators must still adhere to the Administrative Regulations of the New York State Department of Corrections and any relevant state or local laws.

Research sponsored by the Department of Defense (DoD) strictly prohibits involving prisoners of war (POWs), which encompasses any individual captured, detained, or under the control of DoD personnel, including military, civilian, or contractor employees.

Minimal risk, as defined in Subpart C, differs from its interpretation in other federal regulations Per 45 CFR 46.303, minimal risk refers to the likelihood and extent of physical or psychological harm that individuals typically experience in their everyday lives or during standard medical, dental, or psychological evaluations of healthy individuals.

In addition to satisfying the general requirements detailed in the IRB section of this manual, when reviewing research-involving prisoners, the IRB must also meet the following requirements:

 A majority of the IRB (exclusive of prisoner members) must have no association with the prison(s) involved, apart from their membership on the IRB

At least one member of the Institutional Review Board (IRB) must be a prisoner or a qualified prisoner representative, ensuring they have the relevant background and experience However, if a specific research project is reviewed by multiple IRBs, only one of them is required to meet this criterion.

 At least one of the IRB committees will be duly constituted to review research involving prisoners Consultation with ORC is strongly recommended if such research is proposed

6.7.4 Review of Research Involving Prisoners

1 The prisoner representative must review research involving prisoners, focusing on the requirements in Subpart C

2 The prisoner representative must receive all review materials pertaining to the research (same as primary reviewer)

A prisoner representative must be present at any meeting reviewing research involving prisoners; without their presence, the research cannot be reviewed or approved The representative can participate via phone, video conference, or webinar, ensuring they can engage fully as if they were there in person.

4 The prisoner representative must present his/her review either orally or in writing at the convened meeting of the IRB when the research involving prisoners is reviewed

5 Modifications a) Minor modifications to research may be reviewed using the expedited procedure described below, using either of the two procedures described based on the type of modification

On March 19, 2020, modifications that exceed minor changes and require convened IRB review must adhere to the same procedures as the initial review This includes the obligation for the prisoner representative to evaluate the modification and take part in the meeting.

Continuing review processes should adhere to the same protocols as the initial review, ensuring that the prisoner representative is responsible for examining the continuing review materials and actively participating in the meeting.

Research involving prisoner interactions can undergo expedited review if it poses no more than minimal risk, requiring agreement from a prisoner representative This representative may act as a sole reviewer or alongside others, and the same procedures apply for modifications and ongoing reviews Conversely, research without direct prisoner interaction, such as data analysis, may also qualify for expedited review under similar risk conditions, but does not necessitate a prisoner representative's involvement unless designated by the IRB Chair Consistent procedures for initial, modification, and continuing reviews must be maintained.

If a subject becomes a prisoner while enrolled in a research study that was not reviewed according to Subpart C and Subpart C applies, the IRB must:

1 Confirm that the subject meets the definition of a prisoner

2 Terminate enrollment or review the research study under Subpart C if it is feasible for the subject to remain in the study

Before terminating the enrollment of an incarcerated subject in a study, the Institutional Review Board (IRB) must carefully evaluate the associated risks If termination is not feasible due to health or safety concerns, two options arise: first, the subject may remain enrolled while the research is reviewed under Subpart C, with the IRB required to inform the Office for Human Research Protections (OHRP) if certain Subpart C requirements cannot be met but it is deemed in the subject's best interest to continue; alternatively, the subject can be removed from the study while still receiving the study intervention through methods such as compassionate use or off-label use.

If a participant is temporarily incarcerated during a study, they should remain enrolled if their incarceration does not impact the study's outcomes However, if the temporary incarceration affects the study, follow the established guidelines for managing such situations.

The IRB Chair mandates that all research interactions and interventions involving prisoner-subjects, including the collection of identifiable private information, must be halted until the convened IRB reviews and approves any changes to the research protocol.

Upon learning that a previously enrolled human subject has become a prisoner, the convened Institutional Review Board (IRB) must swiftly re-evaluate the research protocol to safeguard the rights and welfare of the now-imprisoned subject If the IRB lacks a prisoner representative, it is essential to consult with a subject matter expert who has the necessary expertise to ensure ethical oversight.

If a prisoner-subject is able to continue giving consent and meets the research protocol requirements, their confinement conditions will not hinder the ethical conduct of the study Provided there are no significant issues obstructing the research involving human subjects, the convened Institutional Review Board (IRB) may approve modifications to the study, allowing the prisoner-subject to remain involved in the research.

6.7.6 Additional Duties of the IRB

Research Involving Children

All research involving children, irrespective of funding source, must adhere to specific requirements that align with Subpart D of 45 CFR 46 for DHHS-funded studies and Subpart D of 21 CFR 50 for FDA-regulated research.

Research involving children must be evaluated by the Institutional Review Board (IRB) and classified into specific categories If multiple study arms are present, a component analysis is required to assess the risk associated with each arm.

45 CFR 46.404; OHRP and if applicable, 21 CFR 50.51; FDA

Research not involving physical or emotional risk greater than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (i.e., minimal risk)

 Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth in Section 6.8.2

45 CFR 46.405; OHRP, and if applicable 21 CFR 50.52; FDA

Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subject

 The risk is justified by the anticipated benefit to the subjects;

 Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth in Section 6.8.2

45 CFR 46.406; OHRP and if applicable 21 CFR 50.53; FDA

Research involving greater than minimal risk and no reasonable prospect of direct benefit to the individual subject, but likely to yield generalizable knowledge about the subject's disorder or condition

 The risk represents a minor increase over minimal risk;

 The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;

 Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth in Section 6.8.2

Research aimed at understanding, preventing, or alleviating serious health or welfare issues affecting children requires specific approvals Federally-funded studies must receive authorization from the Secretary of Health and Human Services, while FDA-regulated research needs the approval of the Commissioner of Food and Drugs For non-federally-funded and non-FDA research, the Institutional Review Board (IRB) will seek guidance from a panel of experts across relevant fields such as science, medicine, ethics, and law The IRB may then approve the research based on the panel's recommendations.

1 That the research in fact satisfies the conditions of the previous categories, as applicable; or

 The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;

 The research will be conducted in accord with sound ethical principles; and

Informed consent will be acquired following the guidelines outlined in this manual, ensuring compliance with all relevant sections Additionally, appropriate measures will be taken to obtain the assent of children, along with the necessary permission from their parents or guardians, as detailed in Section 6.8.2.

The Institutional Review Board (IRB) is responsible for ensuring that appropriate measures are in place to obtain consent from each child's parents or guardians In certain cases, the IRB may determine that the consent of just one parent is adequate for research compliance under sections 404 and 405 This decision regarding parental consent will be recorded in the electronic system for protocols undergoing expedited review, and it will also be reflected in the meeting minutes of the convened committee.

Consent from both parents is required for research to be conducted under 406 & ‘Research not otherwise approvable’ above unless:

1 One parent is deceased, unknown, incompetent, or not reasonably available; or

2 When only one parent has legal responsibility for the care and custody of the child

The IRB may waive the requirement for obtaining permission from a parent or legal guardian if:

1 The research meets the provisions for waiver in Section 5.9; or

If the Institutional Review Board (IRB) finds that a research protocol involves subjects, such as neglected or abused children, where obtaining parental or guardian consent is not feasible, it may allow for a waiver of this requirement This waiver must be accompanied by a suitable protective mechanism for the child participants and must comply with federal, state, and local laws The selection of this protective mechanism should consider the specific activities outlined in the protocol, as well as the associated risks and benefits for the research subjects, taking into account their age, maturity, status, and overall condition.

Permission from parents or legal guardians must be documented in accordance with and to the extent required by Section 5.7

Assent refers to a child's active agreement to participate in research, requiring more than mere compliance or lack of resistance When evaluating a child's capacity for assent, the IRB must consider the nature of the research, along with the children's ages, maturity, and psychological states Given the diverse abilities within the minor population, some children may not possess the cognitive or developmental capacity to provide assent, irrespective of their chronological age Consequently, the IRB may mandate that the principal investigator develop a plan to assess and document each child's ability to assent and comply with the study requirements.

On March 19, 2020, the Institutional Review Board (IRB) may waive the requirement for children's assent in research if it determines that their ability to provide informed consent is significantly limited This waiver is applicable when the research offers important direct benefits to the children's health or well-being that are only accessible through participation in the study Even if the IRB finds that the children are capable of assenting, it can still waive this requirement under specific circumstances outlined in the Waiver of Informed Consent section of the manual.

Each protocol is unique and is reviewed by the IRB accordingly As such, the IRB’s decision regarding assent (and documentation thereof) may necessarily vary from the general parameters below

Assent will be required for:

Non-therapeutic protocols require documented assent from participants For individuals aged 12 to 17, this is achieved through a simplified assent form that the child must sign For those aged 7 to 11, documentation in the research record is necessary to confirm that the assent discussion took place and the child's agreement was obtained.

When considering potentially therapeutic protocols that are FDA-approved or investigational, it is important to recognize that alternatives with similar risk/benefit profiles may exist outside of research To ensure ethical compliance, assent must be documented appropriately: for children aged 12-17, an assent form with simplified consent information is required, while for those aged 7-11, a note in the research record confirming the discussion and the child's agreement is necessary.

The therapeutic protocol under consideration involves the experimental use of FDA-approved drugs, devices, radiation, and procedures, with specific attention to dosages and scheduling For participants aged 12 to 17, documentation of assent is required through a simplified assent form that the child must sign In the case of participants aged 7 to 11, a note must be recorded in the subject's research file indicating that a discussion took place and the child's agreement was obtained.

Protocols that fall outside the defined categories but still require assent by the NCI CIRB for cooperative oncology studies or as mandated by the IRB must have documented consent For children aged 7 to 11, this documentation should include a note in the research record confirming that a discussion took place and the child's agreement was secured.

1 Non-therapeutic protocols where results of biological tests are required in order to determine eligibility for potentially therapeutic protocols (certain COG protocols)

Experimental therapeutic protocols may be necessary for children when standard treatment options are either unavailable or present a less favorable risk/benefit profile Participation in these protocols can be crucial for the health and well-being of pediatric patients facing challenging medical conditions.

3 Studies where the subject population is too young, or the capability of some or all of the children is so limited, that they cannot reasonably be consulted

Whether assent is required or waived, no physical or chemical means of restraint may be used on a minor subject unless specifically approved prior to use by the IRB

This document serves as a clear and simplified version of the approved consent form for the study, ensuring it is accurate and complete It is designed to be easily understood by a twelve-year-old, making it accessible to those around the 7th-grade reading level.

Investigators should create an age-appropriate and study-specific assent form that considers a child's typical experiences and understanding This document must treat the child with respect while clearly conveying essential information about the study.

1 Tell why the research is being conducted;

2 Describe what will happen and for how long or how often;

3 Say it's up to the child to participate and that it's okay to say no;

4 Explain if it will hurt and if so for how long and how often;

5 Say what the child's other choices are;

6 Describe any good things that might happen;

7 Say whether there is any compensation for participating; and

6.8.2.3 Children who are Wards (‘Foster Children”)

Persons with Impaired Decision-Making Capacity

All research involving adults with impaired decision-making capacity must adhere to the outlined requirements, regardless of the funding source It is essential to consult Section 5.5 for the necessary procedures to determine a subject's capacity to provide consent for participation in research.

To include a specific population in research, the investigator must provide a compelling justification to the IRB, demonstrating that the research objectives cannot be achieved without their participation.

A legally authorized representative (LAR) must provide permission for a patient’s participation in research, aiming to ascertain the patient's preferences if they were competent, or to act in the best interest of the individual if their wishes are unclear Whenever feasible, the subject's assent should be sought Additionally, if the subject's condition allows for the possibility of regaining decision-making capacity, the investigator is required to revisit the consent process and obtain the subject’s consent to continue in the study.

6.9.1 IRB Composition and Additional Protections

For research involving more than minimal risk, it is essential that at least one member of the Institutional Review Board (IRB) possesses expertise or experience in working with decisionally-impaired subjects during the review process.

For research that presents more than minimal risk and lacks direct benefits for participants, the Institutional Review Board (IRB) may impose additional protective measures for subjects, which could include one or both of the following requirements, as deemed necessary.

1 A documented determination by the IRB that the research is of vital importance, i.e., there is clear and significant evidence that the use of such a procedure or intervention presents a

D a t e : 3 / 1 9 / 2 0 2 0 reasonable opportunity to further the understanding of the etiology, prevention, diagnosis, pathophysiology, or alleviation or treatment of a condition or disorder; and/or

2 Consultation with one or more representatives of a relevant advocacy group

As with any study, the IRB retains the right to have a member of the IRB or ORC to monitor/witness the consent processes with the patient’s LAR

(See Section 5.5 for general discussion of the consent process required to determine the decision-making capacity of all potential research subjects.)

1 Certain individuals, such as those with severe dementia, or severe mental retardation, will have a diminished capacity to provide consent For these individuals, see the section on 'Surrogate Consent,' below

2 For other individuals, it will not always be easy to predict whether capacity will be diminished given the following:

 Many individuals with psychiatric illnesses have the capacity to provide consent

 Medical illnesses (e.g cerebral insult) may be accompanied by an impaired capacity to consent

 Upon learning of a serious diagnosis (e.g cancer), psychological "shock" may temporarily impair a person's capacity to provide consent, although the illness does not affect decisional capacity in and of itself

 Individuals who are intoxicated with alcohol or with drugs may be unable to consent to research until the intoxication resolves

In assessing capacity, it is important to note that capacity is neither a constant nor an absolute For example:

 Stroke victims may not have the capacity to consent to research immediately after the onset of stroke, but may develop capacity as recovery progresses

Patients with early-stage Alzheimer's disease can initially provide informed consent for research participation; however, as the condition advances, they may lose the ability to make decisions regarding their continued involvement or withdrawal from the study.

 Patients with schizophrenia often experience acute psychotic episodes followed by periods of lucidity

 Patients who learn they are terminally ill, often experience an initial short-lived period of emotional shock and denial which impairs their capacity to provide consent

The requisite level of capacity will necessarily vary from study to study and will depend on:

 The complexity of the information being presented, and

 The relative risks and benefits of the study (deciding to participate in a blood drawing protocol is 'easier' than deciding to participate in an experimental drug trial)

When creating a research proposal, it is crucial for the investigator to assess whether any participants may lack the capacity to provide informed consent, either at the outset or during the study If participants exhibit diminished capacity, the investigator must evaluate whether this impairment is temporary (such as due to shock from a medical diagnosis or intoxication), permanent (like severe intellectual disability), progressive (as seen in Alzheimer's disease), or fluctuating (as in bipolar disorder).

In research protocols involving participants with fluctuating or limited decision-making capacity, it is essential for the Institutional Review Board (IRB) to ensure that investigators maintain continuous communication with caregivers In certain situations, periodic re-consent should be considered Additionally, utilizing third-party consent monitors during recruitment and the consent process, as well as implementing waiting periods, can provide subjects with ample time to contemplate the information presented to them.

Investigators can facilitate voluntary and informed decision-making for individuals with decisional impairments regarding research participation through various methods These methods may include repetitive teaching, group sessions, audiovisual presentations, and recall tests, alongside follow-up questions to gauge understanding Additional strategies encompass recording consent interviews, obtaining second opinions, employing independent consent observers, providing interpreters for hearing-impaired participants, allowing a waiting period before enrollment, and involving trusted family members or friends in the decision-making process.

Investigators and IRB members should recognize that some subjects may experience fluctuations in their decision-making capacity In cases where subjects have inconsistent or diminishing ability to provide consent, implementing a re-consenting process that includes surrogate consent may be essential.

If research participants lose their decision-making capacity after enrollment, the Principal Investigator (PI) must promptly inform the Institutional Review Board (IRB) and the Office of Research Compliance (ORC) Additionally, the PI is tasked with creating a monitoring plan that adheres to established guidelines for managing research subjects with impaired decision-making abilities.

The IRB may mandate that investigators engage independent, qualified professionals—unaffiliated with the study and knowledgeable about consent capacity—to evaluate whether potential subjects can provide voluntary, informed consent, based on the study's risk/benefit ratio and the inclusion of adults who can or cannot consent for themselves.

If the IRB requires such formal documentation of a subject's capacity, the following statement is added to the end of the consent form:

I, a licensed health care provider, confirm through my signature that I interviewed (name of patient) on (date) Based on my assessment, I have determined that s/he does _ does not _ possess the capacity to consent to participation in this research activity Specifically, s/he is is not able to understand that this activity is research rather than standard treatment, the associated risks and benefits, the available alternatives to participation, and that choosing not to participate will not affect his/her clinical care.

Some individuals may oppose participating in a research study even if their legally authorized representative (LAR) has granted permission It is essential to ensure that participation is entirely voluntary, and no subject should ever be subjected to force or coercion.

When subjects lack the capacity to give consent, investigators may obtain permission from the legally authorized representative of a subject as described below

Individuals deemed unable to consent for research participation should be informed about the study in a manner they can understand Whenever feasible, their assent should be obtained through a signed and dated informed consent or separate assent form It is crucial to respect any objections raised by the individual regarding participation.

Where subjects lack the capacity to give consent, surrogate consent may be obtained from the subject’s legally authorized/empowered representative (as defined in Section 5.2)

Definitions

Biological products encompass a diverse array of items, including vaccines, blood components, allergenics, somatic cells, gene therapies, tissues, and recombinant therapeutic proteins These biologics may consist of sugars, proteins, nucleic acids, or complex combinations of these substances, and can also include living entities like cells and tissues Sourced from various natural origins—human, animal, or microorganisms—biologics can be produced through biotechnology and other advanced methods Generally, the term "drugs" also refers to these therapeutic biological products.

Clinical investigation refers to experiments involving a test article and one or more human subjects, which may require prior submission to the Food and Drug Administration (FDA) under sections 505(i) or 520(g) of the act It also includes studies not subject to these submission requirements but intended for future submission or inspection by the FDA as part of a research or marketing permit application However, it excludes experiments governed by part 58 concerning nonclinical laboratory studies.

A dietary supplement is an oral product designed to enhance the diet, containing various dietary ingredients such as vitamins, minerals, herbs, amino acids, and other substances These ingredients may come in the form of concentrates, metabolites, extracts, or combinations of these components, aimed at providing additional nutritional support.

Emergency use refers to administering a test article to a human subject facing a life-threatening situation where no standard treatment exists, and there is insufficient time to secure Institutional Review Board (IRB) approval, as outlined in [21 CFR 56.102(d)].

A Humanitarian Use Device (HUD) is a medical device designed to aid patients in diagnosing or treating diseases or conditions that impact no more than 8,000 individuals annually in the United States.

Investigational Drug Investigational or experimental drugs are new drugs that have not yet been approved by the FDA or approved drugs that are being studied in a clinical investigation

An investigational device refers to any device, including transitional devices, that is under investigation This investigation involves clinical research with one or more subjects to assess the device's safety and effectiveness.

IND IND means an investigational new drug application in accordance with 21 CFR Part 312

IDE IDE means an investigational device exemption in accordance with 21 CFR 812

In vitro diagnostic products (IVDs) are essential tools that include reagents, instruments, and systems designed for diagnosing diseases and assessing health conditions These products play a crucial role in the collection, preparation, and analysis of human specimens, aiding in the treatment, mitigation, and prevention of diseases and their complications.

Non-Significant Risk (NSR) Device A non-significant risk device is an investigational device that does not meet the definition of a significant risk device

Significant Risk (SR) Device Significant risk device means an investigational device that:

1 Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; or

2 Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject; or

The use of this substance is crucial for diagnosing, curing, mitigating, or treating diseases, and it plays a significant role in preventing health impairments However, it also poses a potential serious risk to the health, safety, or welfare of individuals.

4 Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject

FDA Exemptions

The following categories of clinical investigations are exempt from the requirements of FDA regulations for IRB review:

Emergency use of a test article must be reported to the Institutional Review Board (IRB) within five working days, and any further use of the test article at the institution requires IRB review, as outlined in [21 CFR §56.104(c)].

Taste and food quality evaluations, along with consumer acceptance studies, indicate that wholesome foods without additives are preferable Foods containing safe levels of ingredients, as determined by the FDA, or agricultural and environmental contaminants approved by the Environmental Protection Agency and the U.S Department of Agriculture, can also be consumed safely.

Clinical Investigations of Articles Regulated as Drugs or Devices

When conducting studies on the safety or effectiveness of medical devices or experiments involving drugs, biologics, dietary supplements, or other compounds regulated by the FDA, investigators must specify on the IRB application whether an Investigational Device Exemption (IDE) or Investigational New Drug (IND) is in place If an IDE or IND is not applicable, the investigator must provide a justification for its absence.

Documentation must be provided by the sponsor or the sponsor-investigator Documentation of the IND/IDE could be a:

1 Industry sponsored study with IND/IDE number indicated on the protocol;

3 Letter/communication from industry sponsor; or

4 Other document and/or communication verifying the IND/IDE

Investigational device studies may be categorized as IDE-exempt or classified as Non-significant Risk (NSR), allowing them to bypass formal FDA approval When a sponsor identifies a study as IDE-exempt or NSR, the investigator must submit documentation justifying this classification for the IRB's review Additionally, if the FDA has made a determination regarding the IDE-exempt or NSR status of the study, that documentation must also be included in the submission.

The IRB will review the application and, based upon the documentation provided, determine:

1 That there is an approved IND/IDE in place;

2 That the FDA has determined that an IND is not required or that a device study is IDE- exempt or NSR; or,

Determining whether an Investigational New Drug (IND) application is necessary, or if a device study is exempt, Non-Significant Risk (NSR), or requires submission to the FDA for an Investigational Device Exemption (IDE) or a determination, involves evaluating specific criteria outlined below.

The IRB cannot grant approval to the research until the IND/IDE status is determined, and, if necessary, an approved IND or IDE is in place

For drugs, an IND is not necessary if the research falls in one of the following seven (7) categories:

Under 21 CFR 312.2(b)(1), research involving a lawfully marketed drug in the United States must meet specific criteria Firstly, the study should not aim to support a new indication or significant labeling changes For prescription drugs, it should not seek to alter advertising substantially Additionally, the research must avoid any factors that could significantly increase risks or diminish risk acceptability Compliance with IRB review and informed consent requirements is essential, as outlined in 21 CFR parts 56 and 50 Furthermore, the study must adhere to 21 CFR 312.7, ensuring it does not promote or commercialize the drug Lastly, it should not intend to invoke FDA regulations for planned emergency research.

NOTE: FDA has provided specific guidance for evaluating whether this exemption applies to studies of marketed drugs/biologics for the treatment of cancer

According to 21 CFR 312.2(b)(2), an Investigational New Drug (IND) application is not required for clinical investigations involving specific in vitro diagnostic biological products, such as blood grouping serum, reagent red blood cells, and anti-human globulin, if these products are intended to confirm diagnoses established by other medically recognized diagnostic methods and are shipped in accordance with 312.160 regulations.

3 21 CFR 312.2(b)(5): A clinical investigation involving use of a placebo is exempt from the requirements of part 312 if the investigation does not otherwise require submission of an IND

According to 21 CFR 320.31(b) and (d), Bioavailability or Bioequivalence (BA/BE) studies are permissible under specific conditions: the drug product must not contain a new chemical entity, should not be radioactively labeled or cytotoxic; the dose must not exceed that specified in the approved labeling; the investigation must comply with IRB review and informed consent requirements; and the sponsor must adhere to the retention requirements for test article samples.

Research involving a radioactive drug or biological product is permissible under 21 CFR 361.1 if it meets specific criteria: it must focus on basic research without immediate therapeutic or diagnostic intentions; approval must come from a Radioactive Drug Research Committee (RDRC) sanctioned by the FDA; the administered dose must not produce any clinically detectable pharmacological effects in humans; and the total radiation exposure must be minimized to the lowest practical amount while still ensuring the study's benefits and remaining within established limits.

The FDA exercises enforcement discretion for research involving cold isotopes of unapproved drugs, provided that specific conditions are fulfilled This research must aim to gather fundamental information about the metabolism of these substances.

The research focuses on the kinetics, distribution, and localization of a drug labeled with a cold isotope in relation to human physiology, pathophysiology, or biochemistry It is important to note that this study does not aim to provide immediate therapeutic, diagnostic, or preventive benefits to participants The administered dose is established to be free from clinically detectable pharmacologic effects in humans, supported by clinical data from published literature and valid human studies Additionally, the cold isotope used meets all relevant quality standards, and the investigation adheres to the necessary requirements for IRB review and informed consent, as outlined in [21 CFR parts 56 and 50].

For clinical investigations of medical devices, an IDE is not necessary if:

The study focuses on a device, distinct from transitional devices, that was commercially available prior to May 28, 1976, and was utilized or examined according to the labeling guidelines that were in place at that time.

The research pertains to a device, distinct from a transitional device, that was introduced into commercial distribution on or after May 28, 1976 The FDA has classified this device as substantially equivalent to one that was already in commercial distribution prior to that date This device is utilized or studied based on the indications specified in the labeling reviewed by the FDA under subpart E of 21 CFR 807, which is part of the determination process for substantial equivalence, commonly referred to as a “510k” device.

The research focuses on a diagnostic device that adheres to the requirements outlined in 21 CFR 809.10(c) It emphasizes that the testing must be noninvasive, should not involve any invasive sampling procedures that pose significant risks, must not intentionally introduce energy into the subject, and cannot be used as a diagnostic procedure without confirmation from an established medical diagnostic product or procedure.

The study focuses on a device that is being evaluated for consumer preferences, modifications, or combinations of multiple devices available in the market, provided that the testing is not aimed at assessing safety or effectiveness and does not pose any risks to participants.

5 The research involves a device intended solely for veterinary use;

6 The research involves a device shipped solely for research on or with laboratory animals and labeled in accordance with 21 CFR 812.5(c);

7 The research involves a custom device as defined in 21 CFR 812.3(b), unless the device is being used to determine safety or effectiveness for commercial distribution

7.3.4 Significant and Non-Significant Risk Device Studies

A device study is a Non-Significant Risk (NSR) Device study if it is not IDE exempt and does not meet the definition of a Significant Risk (SR) Device study

Under 21 CFR 812.3(m), an SR device means an investigational device that:

1 Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;

2 Is purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;

The use of this treatment is crucial for diagnosing, curing, mitigating, or treating diseases, and it also plays a significant role in preventing impairment of human health However, it carries a potential risk that could seriously impact the health, safety, or welfare of individuals.

4 Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject

If the FDA has already determined a study to be SR or NSR, the FDA’s determination is final and the IRB does not have to make the device risk determination

The IRB will evaluate studies proposed as Non-Significant Risk (NSR) during a convened meeting, unless the FDA has already established a device risk determination for the study, to ascertain whether the device is classified as Significant Risk (SR) or NSR.

Diagnostic or Treatment Use of Humanitarian Use Devices

A Humanitarian Use Device (HUD) is a medical device approved for use in treating or diagnosing rare diseases affecting fewer than 8,000 individuals annually in the U.S According to federal law, the use of a HUD at a facility must be approved by an Institutional Review Board (IRB) Once granted approval, a HUD can be utilized like any other approved medical device, although it is important to note that its effectiveness has not been established through clinical trials.

A Humanitarian Device Exemption (HDE) is a premarket approval application submitted to the FDA under 21 CFR Part 814, allowing for an exemption from the effectiveness requirements of the FD&C Act The FDA grants HDE approval based on the assessment that the Humanitarian Use Device (HUD) does not pose an unreasonable risk of illness or injury to patients, and that the health benefits of using the device outweigh potential risks compared to existing treatments An HDE Holder is defined as the individual or entity that receives FDA approval for an HDE.

A Humanitarian Use Device (HUD) can only be utilized in a facility after receiving approval from an Institutional Review Board (IRB), unless specific emergency situations arise The holder of the Humanitarian Device Exemption (HDE) is accountable for ensuring that the HUD is supplied exclusively to facilities that have a properly constituted IRB, which operates in compliance with FDA regulations (21 CFR Part 56) and conducts ongoing reviews of the device's usage.

In clinical investigations involving a Humanitarian Use Device (HUD), compliance with IRB review and informed consent regulations (21 CFR 50 and 56) is mandatory, along with other relevant regulations It is crucial to identify whether the HUD is being evaluated for its approved indications or for alternative uses If the HUD is studied for its approved indications, the IDE regulations at 21 CFR 812 do not apply Conversely, if the HUD is assessed for different indications, the IDE regulations are applicable, necessitating an FDA-approved IDE prior to commencing the clinical investigation of a Significant Risk device.

The guidelines and processes outlined in this manual for research are applicable to clinical investigations of Humanitarian Use Devices (HUDs) This section specifically addresses the diagnostic and treatment applications of HUDs.

Health care providers must secure IRB approval before utilizing a Humanitarian Use Device (HUD) at SBU facilities They are also responsible for adhering to relevant regulations, including medical device reporting, organizational policies, and IRB requirements.

Health care providers must submit specific materials to the IRB when seeking initial approval for the diagnostic or treatment use of a Humanitarian Use Device (HUD) in accordance with its approved labeling indications.

2 A copy of the HDE approval letter from the FDA;

3 A description of the device, such as a device brochure;

4 The patient information packet for the HUD; and

5 The proposed clinical consent process

The Institutional Review Board (IRB) conducts a thorough review of proposals during convened meetings, ensuring the presence of relevant expertise, either from its members or external consultants It assesses the risks outlined in product labeling and related documents, evaluating proposed procedures for risk minimization while weighing these risks against potential patient benefits Additionally, the IRB examines the patient information packet and consent process to ensure that the materials are suitable and effective for the target patient population.

The Institutional Review Board (IRB) can impose restrictions on device usage, mandate extra screening and follow-up procedures, request interim reports, and conduct more frequent reviews than once a year These measures aim to minimize patient risks and ensure the device's safe application within the facility.

Once the HUD usage is authorized, the healthcare provider must submit any proposed modifications to the IRB-approved plan or patient materials for approval before implementation, unless the change is essential to mitigate an immediate risk to a patient Proposed changes must include revised materials or supporting documentation The IRB may utilize expedited review procedures for these changes or refer them to the convened IRB for evaluation.

Healthcare providers must report to the FDA, IRB, and manufacturer/HDE Holder if a Humanitarian Use Device (HUD) may have caused or contributed to a death or serious injury, as mandated by 21 CFR 803.30 and 814.126(a) A serious injury is defined as life-threatening, resulting in permanent impairment or damage, or requiring medical intervention to prevent such outcomes (21 CFR 803.3) These reporting requirements fall under the Medical Device Reporting (MDR) Regulation, specified in 21 CFR Part 803 The IRB will review these reports through expedited or convened review, determining if any modifications to the IRB-approved plan or patient materials are necessary.

Health care providers must submit continuing review materials to the Institutional Review Board (IRB) well ahead of the expiration date to guarantee timely review and re-approval Required submissions include all relevant documentation necessary for the IRB's assessment.

2 The most recent periodic report to the FDA by the HDE holder;

3 The current patient information packet, if applicable;

4 The current consent, if applicable;

5 Any other new relevant information or materials

The IRB may conduct continuing review using expedited review procedures or review by the convened IRB

In emergency situations, a trained and licensed health care provider may utilize a Humanitarian Use Device (HUD) without prior Institutional Review Board (IRB) approval if obtaining such approval would delay necessary treatment that could prevent serious harm or death to a patient The provider is required to notify the Office for Research Compliance (ORC) in writing within five days of the device's emergency use, including details such as the patient's identity, the date of use, and the justification for its application, as stipulated by [21 CFR 812.124].

If a Health and Human Services-approved device is needed in an emergency or when no alternative exists, a licensed healthcare provider should consult the holder of the Humanitarian Device Exemption (HDE) and the Institutional Review Board (IRB) beforehand, if feasible It's essential to obtain informed consent when possible and implement measures to safeguard the patient's well-being, including a structured plan for follow-up examinations and monitoring procedures.

On March 19, 2020, it is essential for healthcare providers to consider the individual needs of patients alongside the known risks and benefits of medical devices Providers are required to submit follow-up reports to both the Humanitarian Device Exemption (HDE) holder and the Institutional Review Board (IRB), while also adhering to medical device reporting regulations.

The IRB may require additional reports, patient protection measures, or other requirement, as appropriate given the specifics of the situation.

Expanded Access to Investigational Drugs, Biologics, and Devices

Expanded access pathways aim to provide investigational medical products to patients lacking therapeutic options who are ineligible for approved therapies or clinical trials This approach allows the use of unapproved medical products outside of clinical trials, prioritizing treatment over research However, since these products have not received FDA approval for safety and efficacy, it is crucial to communicate to patients or their legal representatives that the products may be ineffective and could have unforeseen serious adverse effects, necessitating careful safety monitoring.

Charging for expanded access use of investigational products is discussed in Section 7.6

7.5.1 Expanded Access to Investigational Drugs and Biologics

The FDA's expanded access rule facilitates access to investigational drugs, including biologics, for patients with serious or life-threatening conditions who have no other treatment options This program, often known as compassionate use or treatment use, aims to provide potentially beneficial investigational agents to those in urgent need.

Expanded access to investigational drugs is defined for immediately life-threatening diseases or conditions as those where death is likely within months or where early treatment is crucial to prevent premature death A serious disease or condition significantly affects daily functioning and may involve persistent or recurrent morbidity, although it doesn't need to be irreversible Determining the seriousness of a disease relies on clinical judgment, considering its effects on survival, daily activities, and the potential for progression to a more severe state if left untreated.

Expanded access may be applicable in several scenarios: (1) when a drug has been withdrawn due to safety concerns but still offers benefits that outweigh risks for certain patients; (2) during drug shortages, when a similar, unapproved drug (such as a foreign-approved product) is used for treatment; (3) when an approved drug's availability is restricted by a risk evaluation and mitigation strategy (REMS); and (4) for other specific reasons All these situations are classified as “investigational” under these standard operating procedures (SOPs).

Under the FDA’s expanded access rule, access to investigational drugs for treatment purposes is available to:

 Individual patients, including an emergency [21 CFR 312.310]

 Intermediate-size patient populations [21 CFR 312.315]

 Widespread use under a treatment protocol or treatment IND [21 CFR 312.320]

This section discusses expanded access for individual patients, emphasizing that investigators looking for expanded access for larger populations should consult with the ORC It is important to note that a convened IRB review is typically necessary for intermediate or widespread expanded access unless a waiver has been granted by the FDA.

Physicians interested in obtaining investigational drugs through expanded access must collaborate with the sponsor or manufacturer, the FDA, and the ORC to identify the suitable access method and adhere to regulatory protocols The FDA's website offers detailed information on the expanded access procedures and requirements, along with contact details for further assistance.

7.5.1.1 Expanded Access to Investigational Drugs for Individual Patients

Expanded access to investigational drugs may be sought under an “Access Protocol” or an

Access INDs are encouraged by the FDA as they streamline the review process for safety and other relevant information, typically managed by the sponsor of an existing IND However, they are also available for individual patient treatment in cases where the current IND sponsor declines to oversee the individual use, preferring the physician to act as the sponsor-investigator, or when no existing IND is available.

Before submitting requests to the FDA or IRB for expanded access to an investigational drug, physicians should first reach out to the sponsor or manufacturer This step is crucial to confirm the availability of the investigational drug, assess if the patient can be treated under an existing IND study or sponsor-held Access Protocol, or determine if an Access IND is necessary.

D a t e : 3 / 1 9 / 2 0 2 0 determine if the drug will be provided free or if there will be a charge A Letter of Authorization (LOA) from the sponsor or manufacturer should be obtained

When a commercial sponsor provides access under an Access Protocol, they are responsible for managing the process and obtaining FDA approval, along with fulfilling all sponsor obligations A licensed physician overseeing the administration or dispensing of an investigational drug for expanded access is classified as an "investigator" under FDA regulations and must adhere to all relevant investigator responsibilities as outlined in 21 CFR 312.

If a sponsor or manufacturer refuses to treat a patient under an existing IND study or Access Protocol but is willing to provide the investigational drug, physicians can submit an individual patient Access IND application to the FDA using Form FDA 3926 This streamlined application is specifically designed for such cases and is available on the FDA website Form FDA 3926 allows investigators to request alternative IRB review procedures, enabling the IRB Chair or a designated member to conduct the review instead of the full convened IRB This process, known as "concurrence review," requires the IRB Chair to evaluate the same materials and make the same determinations as the full board Additionally, this review method can be utilized for post-approval reviews, including unanticipated problems and continuing reviews.

In emergency situations where there is not enough time to submit a written application to the FDA before treatment, a request for emergency use can be made via telephone or other rapid communication methods It is essential to submit a written expanded access application within 15 days of receiving authorization from the FDA.

A physician who secures an Access IND is designated as a "sponsor-investigator," assuming the dual responsibilities of both sponsors and investigators as outlined in 21 CFR 312 This includes the obligation to submit IND safety reports, annual reports, and ensure proper maintenance of drug accountability records.

Before starting treatment with an investigational drug, it is essential to obtain Institutional Review Board (IRB) approval unless the criteria for an emergency use exemption are met If the FDA has authorized alternative IRB review procedures, typically indicated by a request on Form FDA 3926, the review may be carried out by the IRB Chair or a designated representative If not, the review must involve the convened IRB.

Physicians administering investigational drugs through compassionate use must create and submit a comprehensive treatment and monitoring plan tailored to the drug's characteristics and the patient's specific needs This plan should incorporate vigilant monitoring to identify any potential complications associated with the drug's use.

To request IRB approval for single patient expanded access, investigators should contact the ORC and submit the following via the IRB electronic management system:

1 A complete patient history justifying the use, and details concerning the plan for treating and monitoring the patient;

2 A copy of the letter of authorization (LOA) from the Commercial Sponsor or

Manufacturer or other documentation supporting sponsor/manufacturer approval;

3 A copy of the information submitted to the FDA (and FDA approval, if available);

4 A copy of the Investigator’s Brochure or similar documentation that provides information regarding the potential risks and benefits of the investigational drug;

5 A copy of the draft informed consent document

The IRB can review an expanded access application before receiving FDA approval; however, it cannot grant final approval until the FDA approval documentation is submitted Following its review, the IRB will provide the investigator with written documentation.

Charging Subjects for Investigational Products

The FDA allows charging subjects or their insurers for investigational products, provided these charges meet specific criteria However, this approval does not relieve the investigator and Institutional Review Board (IRB) of their ethical responsibilities, which include minimizing risks to participants (Beneficence), ensuring equitable distribution of research risks and burdens (Justice), and guaranteeing that subjects are adequately informed without undue pressure to accept unacceptable risks or costs for potential benefits (Respect for Persons) All costs to participants or insurers must be clearly outlined in both the IRB application and the informed consent document.

7.6.1 Charging for Investigational Medical Devices and Radiological Health Products

Under IDE regulations, sponsors are permitted to charge for investigational devices, but the fees must not exceed the costs associated with manufacturing, research, development, and handling [21 CFR 812.7(b)] In the IDE application, sponsors are required to justify the proposed charges, specify the amount, and clarify how the charge does not equate to commercialization [21 CFR 812.20(b)(8)].

7.6.2 Charging for Investigational Drugs and Biologics

In 2009, FDA updated its rules at 21 CFR 312 regarding charging for Investigational Drugs Under an IDE These rules:

 Provide general criteria for authorizing charging for an investigational drug [21 CFR 312.8(a)]

 Provide criteria for charging for an investigational drug in a clinical trial [21 CFR 312.8(b)]

 Set forth criteria for charging for an investigational drug for an expanded access for treatment use [21 CFR 312.8(c)]

 Establish criteria for determining what costs can be recovered when charging for an investigational drug [21 CFR 312.8(d)]

Additional information is available in FDA guidance: Charging for Investigational Drugs Under an IND — Questions and Answers.

Responsibilities for FDA-Regulated Research

Under FDA regulations, clinical investigators are required to possess the necessary training and experience to ensure the proper conduct of clinical studies They lead the research team and must pledge to the study sponsor their commitment to adhere to federal regulations concerning investigational drugs and devices before commencing participation in any clinical investigation.

2 Ensuring the informed consent is obtained from subjects in accordance with IRB approval

3 Retaining records for two years following the date the marketing application is approved by FDA or withdrawn and making those records available for inspection

4 Furnishing the required reports to the sponsor, including reports of adverse events and study completion

Timely reporting to the Institutional Review Board (IRB) is essential, particularly regarding any changes in research activities that may pose immediate hazards to participants This includes notifying the IRB of protocol deviations and unanticipated problems that could introduce risks to participants or others involved in the study For detailed procedures, refer to Section 8 of the Standard Operating Procedures (SOPs).

It is essential to inform potential participants that the test articles, such as drugs, are being utilized for investigational purposes Additionally, it is crucial to ensure compliance with the requirements for obtaining informed consent and securing Institutional Review Board (IRB) review and approval.

7 Ensuring that changes are not implemented without prospective IRB approval, unless required to eliminate immediate hazard to participants

8 Complying with the requirements of the Controlled Substances Act

9 Complying with all FDA test article requirements

10 Adequately maintaining control of test articles, including appropriate tracking documentation for test articles to the extent that such control and documentation are not centrally administered

11 Supervising the use and disposition of the test article

12 Disclosing relevant financial information and conflicts of interest

13 Ensuring that all associates, colleagues, and employees assisting in the conduct of the investigation(s) are informed about their obligations in meeting the above commitments

1 The clinical investigator must comply with the requirements specified in FDA Form 1572:

 Personally conduct or supervise the described investigation(s)

All studies must be conducted in line with the approved IRB protocols, and any modifications to these protocols should be communicated to the sponsor, unless changes are required to ensure the safety, rights, or welfare of the participants.

 Comply with all requirements regarding the obligations of clinical investigators and all other pertinent regulatory requirements

Investigators must promptly report any serious adverse events to the sponsor, regardless of their relation to the drug, including those specified in the protocol or investigator brochure This report should assess the likelihood of the drug causing the event Serious adverse events, such as all-cause mortality, must be reported per the protocol unless evidence indicates a causal link between the drug and the event, such as death from anaphylaxis, in which case immediate reporting is required Nonserious adverse events should also be recorded and reported to the sponsor according to the specified reporting timetable in the protocol.

 Read and understand the information in the investigator's brochure, including the potential risks and side effects of the drug

 Ensure that all associates, colleagues, and employees assisting in the conduct of the study(ies) are informed about their obligations in meeting the above commitments

 Ensure that an investigation is conducted according to the signed statement (Form FDA

1572), the investigational plan, and applicable regulations

 Protecting the rights, safety, and welfare of participants under the clinical investigator’s care

Clinical investigators conducting drug or biologic research must adhere to the University’s Investigational Drug Service plan, ensuring proper storage, security, and dispensing of the substances They are also responsible for maintaining accurate records of accountability, including the accounting, return, and disposition of the drugs or biologics in accordance with the study protocol.

At the University Hospital's Health Sciences Center, Cancer Center, and Ambulatory Surgery Building, the Principal Investigator (PI) will assign the Investigational Drug Service within the Pharmacy Department to manage the accountability of drugs and biologics This includes overseeing their storage, dispensing, labeling, and distribution.

Research conducted at any campus site will be reviewed and evaluated by the IRB, in collaboration with the Investigational Drug Service, at the time of submission.

The Principal Investigator (PI) overseeing investigational drug studies must submit the study for ancillary review within the electronic management system to the Investigational Drug Service, ensuring that the status of Institutional Review Board (IRB) approval is monitored and verified.

 The PI must inform the IRB and Pharmacy Service when a study involving investigational drugs has been terminated by the sponsor

3 The clinical investigator will administer the drug only to participants under the clinical investigator’s personal supervision or under the supervision of a sub-investigator responsible to the clinical investigator

4 The clinical investigator will not supply the investigational drug to any person not authorized to receive it

Clinical investigators must keep thorough records of the drug's distribution, detailing dates, quantities, and participant usage, in compliance with the guidelines established by the Investigational Drug Service.

Upon the termination, suspension, discontinuation, or completion of an investigation, the clinical investigator is required to return any unused drug supplies to the sponsor or arrange for their disposal, as permitted by the sponsor.

A clinical investigator must prepare and maintain comprehensive and precise case histories that document all relevant observations and data for each individual receiving the investigational drug or serving as a control in the study.

Case histories encompass case report forms and essential supporting documents, such as signed consent forms and medical records, including physician progress notes, hospital charts, and nurses' notes Each individual's case history will confirm that informed consent was secured before their participation in the study.

A clinical investigator is required to maintain records for two years after the approval date of a marketing application for the drug being studied If no application is filed or if the application is not approved, records must be kept for two years after the investigation ends and the FDA is notified [21 CFR §312.62]

9 A clinical Investigator must maintain the following:

 Records of receipt and disposition of drugs

 List of any co-investigators with their curriculum vitae

 Certification that all physicians, dentists, and/or nurses responsible in the study have appropriate valid licenses for the duration of the investigation, and

The article highlights case histories that provide detailed documentation on the effects of drugs, with a particular focus on toxicity and potential adverse events It emphasizes the importance of reporting any unforeseen issues that may pose risks to participants or others, in compliance with Section 8 regulations.

 Other documents as outlined in the Human Research Protection Program Standard Operating Procedures

1 The clinical investigator must sign an agreement with the sponsor that includes a statement of the clinical investigator’s commitment to: [21 CFR §812.43(c)(4)]

 Conduct the investigation in accordance with the agreement, the investigational plan, applicable FDA regulations, and conditions of approval imposed by the reviewing IRB or FDA;

 Supervise all testing of the device involving human participants; and

 Ensure that the requirements for obtaining informed consent are met

2 The clinical investigator must ensure that an investigation is conducted according to the signed agreement, the investigational plan and applicable FDA regulations

Policy on Research with Dietary Supplements

Research on dietary supplements may or may not be regulated by the FDA, depending on the intent of the study According to the Dietary Supplement Health and Education Act (DSHEA) of 1994, dietary supplements are not classified as drugs and do not require premarket approval if marketed solely to affect the body's structure or function, rather than for therapeutic purposes If a clinical investigation aims to assess a dietary supplement's impact on body function, it falls outside FDA oversight Conversely, if the study seeks to evaluate the supplement's ability to diagnose, cure, mitigate, treat, or prevent a disease, it is subject to FDA regulations Regardless of FDA oversight, all research involving dietary supplements must be reviewed by an Institutional Review Board (IRB).

The necessity of an Investigational New Drug (IND) application for studies on dietary supplements depends on the study's intent If the research aims solely to assess the dietary supplement's effects on bodily structure or function, an IND is not needed However, if the study seeks to evaluate the supplement's potential to diagnose, cure, mitigate, treat, or prevent diseases, an IND is required in accordance with part 312.

When conducting research involving a test article, investigators must provide the Institutional Review Board (IRB) with comprehensive information to ensure approval criteria are met and to assess whether an Investigational New Drug (IND) application is necessary Applications should include detailed information comparable to that found in a drug protocol, reflecting the anticipated level of risk associated with the research At a minimum, the research plan must include essential details about the supplement, such as its name, manufacturer, formulation, dosage, and method or route of administration.

The administration of the product requires a comprehensive understanding of its mechanism of action, known drug interactions, and risk profile, alongside an IND number or justification for its absence Documentation of approval for human use and certification of quality or purity is essential An accountability plan must outline the product's storage, dispensing, usage tracking, and disposal or return processes Additionally, if the study involves more than minimal risk, a Data and Safety Monitoring plan is necessary to ensure participant safety.

8 Unanticipated Problems Involving Risks to Subjects or Others (a type of ‘Reportable New Information-RNI’)

Policy

The University adheres to DHHS and FDA regulations, requiring institutions to maintain written policies for reporting unanticipated problems that pose risks to subjects or others These reports must be submitted to the IRB, institutional officials, and pertinent federal agencies and departments.

Definitions

Unanticipated problems involving risk to subjects or others: refers to any problem, event, or new information that:

Unexpected events in research can arise when they differ significantly in nature, severity, or frequency from what is outlined in the IRB-approved research protocol and informed consent documents, as well as the characteristics of the subject population under study.

2 Indicates that subjects or others are at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized

3 Is possibly or probably related to the research procedures described in the protocol-related documents

Note: Unanticipated problems occurring in subjects whose participation in the study ended within 30 days of the unanticipated problems are considered applicable to this policy

An Adverse Event (AE) refers to any unfavorable physical or psychological occurrence experienced by a human subject involved in research This includes unintended events such as abnormal laboratory findings, symptoms, or diseases that may arise in connection with the research or the use of a medical investigational test article.

A Serious Adverse Event (SAE) refers to a critical health occurrence that can threaten life or result in significant consequences This includes situations such as hospitalization of a previously healthy individual, extended hospitalization for someone already admitted, persistent disability, congenital anomalies, or birth defects Additionally, an SAE may involve events that endanger the patient and necessitate medical or surgical intervention to avert these serious outcomes.

An Unexpected Adverse Event (UAE) refers to any adverse occurrence or reaction that deviates from the details outlined in the informed consent, investigator brochure, or product labeling Additionally, it does not align with the risk information provided in the general investigational plan or proposal.

An Adverse Device Effect (ADE) refers to any unexpected adverse event or effect linked to the use of a medical device that was not anticipated or documented in the study protocol or Investigator’s Brochure.

Related: An event is “related” if it is likely to have been caused by the research procedures

Unexpected death refers to the demise of a research participant where the risk of death was not anticipated, as outlined in the protocol, informed consent, or sponsor documentation This term excludes fatalities linked to terminal illnesses unless the research intervention is proven to have accelerated the subject's death Additionally, if a subject's death is assessed to be unrelated to the research, it does not qualify as an "unexpected death" under the reporting guidelines.

Procedures

The following procedures describe how unanticipated problems involving risk to subjects or others are handled in research conducted under the auspices of the University

Investigators must report the following problems to the IRB (see Section 8.3.2 for timelines)

1 Serious adverse events which in the opinion of the principal investigator are both unexpected and related to the research activity

Adverse events, excluding serious adverse events (SAEs), that the principal investigator believes qualify as unanticipated problems must meet specific criteria These events should be unanticipated, related to the research, and present an increased risk to subjects or others involved in the study.

3 An unanticipated event related to the research that exposes subjects to potential risk

4 An unanticipated event related to the research that exposes individuals other than the research subjects (e.g., investigators, research assistants, students, the public, etc.) to potential risk

5 Information that indicates a change to the risks or potential benefits of the research For example:

 An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits may be different than initially presented to the IRB

 A paper is published from another study that shows that the risks or potential benefits of the research may be different than initially presented to the IRB

7 Incarceration of a subject in a protocol not approved to enroll prisoners

8 Changes increasing the risk to subjects and/or significantly affecting the conduct of the trial

9 Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a research subject

10 Complaint of a subject when the complaint indicates unexpected risks or cannot be resolved by the research team

A protocol violation occurs when there is an accidental or unintentional alteration to the IRB-approved protocol, which can lead to harm for subjects or others involved Such violations may also suggest an increased risk of harm to these individuals.

12 Event that requires prompt reporting to the sponsor

13 Sponsor imposed suspension for risk

14 Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol

Unanticipated adverse device effects refer to serious health or safety issues, including life-threatening problems or fatalities, linked to a medical device that were not previously identified in the investigational plan or application These effects can significantly impact the rights, safety, or welfare of subjects involved in clinical trials, as outlined in 21 CFR 812.150(a).

Any other event that indicates subject or others might be at risk of serious, unanticipated harms that are reasonably related to the research

Unanticipated Problem Reports, also known as 'Reportable New Information,' must be submitted to the ORC promptly, ideally within five working days of the incident or upon receipt by the University Investigator if the subject is not affiliated with the University.

Problems/AE’s/SAE’s that occur that are anticipated should be submitted as a cumulative summary report (by sponsor, if applicable) required at time of Continuing Review

8.3.3 IRB Procedures for Handling Reports of Possible Unanticipated Problems

8.3.3.1 Review of Unanticipated Problem Reports: University Subjects

Unanticipated Problem Reports will be evaluated by IRB staff to verify if the incident qualifies as an unanticipated problem, consulting with the IRB Chair or AVP-RC when necessary, and will subsequently make an initial decision on the appropriate course of action.

When an unanticipated problem arises, it is forwarded to the IRB Chair for evaluation If immediate action is deemed necessary, the Principal Investigator (PI) will be informed of the required steps to protect the rights and welfare of subjects, pending a full committee review In the absence of the IRB Chair, the AVP-RC or Institutional Official (IO) will make decisions regarding immediate protective measures If no immediate action is needed, the issue will be scheduled for a comprehensive review at the next IRB meeting, which may include a pre-review by one or more IRB members.

8.3.3.2 Review of UP Reports: Non-SBU Subjects

Unanticipated Problem Reports concerning subjects or others not enrolled through the

The IRB staff will review the university's submission to ensure it meets the criteria for an unanticipated problem (UP) This review will verify that both the sponsor and the FDA have been informed as required by the UP/USAE form Additionally, the Institutional Official (IO) will notify the Office for Human Research Protections (OHRP) in compliance with the Federalwide Assurance (FWA) requirements, and the report along with the study history will be included in the agenda for the relevant IRB meeting.

For studies under External IRB oversight, the report will be included in the agenda of the next meeting, with the corresponding form filed in the relevant IRB records The ORC reviewer has the option to refer the USAE to an IRB member or the full committee for evaluation An acknowledgment letter for submitted USAEs will only be issued to the Principal Investigator if the IRB decides that additional action or clarification is necessary.

If the Institutional Review Board (IRB) determines that an event constitutes an unanticipated problem posing risks to subjects or others, as defined by policy, it may suggest various actions in response.

 Requiring modifications to the protocol

 Revising the continuing review timetable

 Providing additional information to current subjects (e.g whenever the information may relate to the subject’s willingness to continue participation)

 Providing additional information to past subjects

 Requiring additional training of the investigator and/or study staff

 Requirement that current subject’s re-consent to participation

 Referral to other organizational entities (e.g., legal counsel, risk management, institutional official)

 Other actions appropriate for the local context

If a report indicates a potential risk to participant safety, the Institutional Review Board (IRB) has the authority to immediately suspend or terminate the research study Such actions will be promptly documented and reported in writing to the Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA), if applicable, by the Institutional Official (IO).

If the IRB determines that an event is an unanticipated problem posing risks to subjects or others, or if suspension or termination of approval is necessary, it will take appropriate action based on its findings.

1 Notify the investigator in writing of its findings, with copies to the chair of the investigator’s department and/or research unit, and the investigator’s supervisor; and

2 Report its findings and recommendations to the IO for further reporting to the appropriate federal officials (OHRP, and FDA)

Any unanticipated problems involving risks to subjects or others occurring in DoD-supported research will be reported within thirty (30) days to the DoD human research protection officer

Policy

It is the policy of the IRB to be notified of any protocol deviations or exceptions that result in an increase in risk or a decrease in benefit to subjects

The following procedures describe how protocol exceptions and deviations are reported to the IRB.

Protocol Exceptions

Protocol exceptions occur when adhering to specific procedures outlined in a protocol may not serve the best interests of an individual subject For instance, if a subject has an allergy to one of the medications included as supportive care, it may be necessary to deviate from the established protocol to ensure their safety and well-being.

Exceptions in research protocols require prior approval from both the sponsor and the Institutional Review Board (IRB) These exceptions should be submitted through the electronic management system, and depending on their nature, they may qualify for expedited review For IRB approval, it is essential that these exceptions do not increase risk, diminish benefits, or compromise the rights, safety, and welfare of subjects, nor affect the integrity of the resulting data.

A protocol exception does not need prior approval from the sponsor and Institutional Review Board (IRB) if it is necessary to prevent immediate harm to the subject It is essential to report such incidents using the specified application for IRB review.

Protocol Deviations (a type of ‘Reportable New Information; RNI’)

Protocol deviations: Circumstances that are unanticipated and happen without any prior sponsor or IRB approval (e.g protocol visit scheduled outside protocol window, blood work drawn outside protocol window, etc.)

All deviations must be reported to the ORC through the electronic management system, except for minor scheduling deviations of study visits that are unavoidable and do not affect subject safety.

Deviations are assessed to determine if they are minor and do not affect subject safety, acknowledged by the ORC, or if they signify noncompliance Noncompliance cases are evaluated by the IRB to classify them as non-serious, serious, or continuing, with the latter two requiring reporting to the OHRP and relevant federal agencies, such as the FDA, as well as sponsors when applicable Additionally, deviations may involve unanticipated problems that pose risks to subjects or others, which the IRB reviews to confirm their status If confirmed as unanticipated problems, these must also be reported to the OHRP and other relevant entities For more details on unanticipated problems, refer to section 8.

Reporting & Review

The IRB staff will assess the submitted information and determine whether it requires expedited review, IRB chair review, or a full committee review The results of this evaluation will be uploaded to the electronic management system for the investigator's review and any necessary actions If the information raises serious concerns, the staff will promptly engage the Chair, AVP-RC, or IO before the IRB meeting to take any necessary actions to ensure the safety of enrolled subjects.

10 Complaints and Non-compliance (types of ‘Reportable New Information- RNI’)

Policy

The University is dedicated to safeguarding the rights, safety, and welfare of human subjects in research by thoroughly reviewing all complaints and allegations of non-compliance, taking appropriate actions to uphold ethical research practices.

The following procedures describe how complaints and allegations of non-compliance are handled by the IRB.

Definitions

Non-compliance refers to the failure to adhere to the regulations and policies outlined in this document, as well as not following the determinations made by the IRB This non-compliance can range from minor or sporadic issues to serious or ongoing violations.

Serious non-compliance refers to the failure to adhere to the regulations and policies outlined in this document, as well as the determinations made by the Institutional Review Board (IRB) Such non-compliance, as assessed by the IRB Chair or the convened IRB, can elevate risks to research subjects and diminish potential benefits.

On March 19, 2020, it was emphasized that conducting non-exempt research without prior Institutional Review Board (IRB) approval undermines the integrity of the human research protection program Additionally, involving subjects in research activities without their informed consent—unless consent was explicitly waived by the IRB—constitutes serious noncompliance.

Continuing non-compliance refers to a persistent pattern of non-compliance that indicates, according to the IRB Chair or convened IRB, a probable continuation of such behavior without intervention This includes situations where non-compliance persists despite previous IRB interventions and instances where there is a failure to address requests aimed at resolving the non-compliance issue.

Allegation of Non-Compliance: An unproved assertion of non-compliance

A finding of non-compliance occurs when an allegation is substantiated or a report is clearly validated, such as an audit revealing an unsigned consent document or an investigator admitting to willful protocol violations These situations require no additional verification, resulting in confirmed findings of non-compliance Once established, these findings must be classified as serious, non-serious, or continuing.

Complaints

Complaints and concerns received by the ORC from investigators, subjects, and other parties will be reviewed in collaboration with the IRB Chair, AVP-RC, and/or IO as necessary The IRB Chair will conduct a preliminary assessment to determine if the complaint necessitates an immediate suspension of the research project If a suspension is deemed necessary, the procedures outlined in Section 3.11.1 will be implemented.

If the complaint meets the definition of non-compliance, it will be considered an allegation of non-compliance according to Section 10.4

If the complaint meets the definition of an unanticipated problem involving risk to subjects or others, it will be handled according to Section 8.

Non-compliance

Investigators and study staff must report any instances of potential non-compliance, with the Principal Investigator (PI) being responsible for notifying the Office of Research Compliance (ORC) about such occurrences Additionally, any individual or employee can report observed or suspected non-compliance to the ORC, provided they do so in good faith while ensuring confidentiality and cooperating with any reviews conducted by the ORC, Institutional Review Board (IRB), or relevant institutional bodies.

If there is uncertainty about the need to report noncompliance, individuals such as investigators or study staff can reach out to the ORC staff for an informal discussion regarding the situation.

Non-compliance reports must be submitted to the ORC within ten working days of discovery, either verbally or in writing These reports should provide a comprehensive description of the noncompliance and detail the personnel involved Complainants have the option to remain anonymous.

10.4.1 Review of Allegations of Non-compliance

Allegations of non-compliance will be initially assessed by the IRB Chair for merit, especially in cases involving multiple studies or off-site IRB oversight, which will be reviewed at the next scheduled meeting The IRB Chair will examine all relevant documents related to the allegation and the study, accessible through the electronic management system If non-compliance poses a risk to subject safety, the IRB Chair, or the AVP-RC or IO in their absence, has the authority to implement immediate actions such as study or enrollment suspension before a full committee review.

Allegations of non-compliance considered valid by the IRB chair will be reviewed at the next full committee meeting If an allegation is directed at a specific individual, that person will be informed of the allegation by the IRB Chair or ORC staff and will have the opportunity to respond prior to the meeting, if feasible.

The IRB will assess the allegation's validity and may seek additional information from the reporting party If necessary, the IRB can establish an ad hoc committee to provide expertise and assist in the review and fact-gathering process related to the research in question The findings of this committee are then communicated through a written report presented at a convened meeting, or delivered verbally, involving members from the ORC and/or IRB.

If it is concluded that noncompliance did not happen because the incident fell within the boundaries of an approved research protocol, this finding will be documented in writing and communicated to the Principal Investigator (PI) and the reporting party, if relevant A copy of the determination letter will also be provided to the Institutional Official (IO) when they and other involved parties were informed at the beginning of the process.

If a determination is made that the reported allegation of non-compliance is true, the non- compliance will be processed according to Section 10.4.2 Review of Findings of Non- compliance

10.4.2 Review of Findings of Non-compliance

Noncompliance is not serious or continuing:

When the IRB identifies noncompliance that is neither serious nor continuing, the ORC staff will provide a written report to the Principal Investigator (PI) and, if relevant, the reporting party This report includes a requirement to develop a corrective action plan to mitigate future noncompliance Should the PI decline to cooperate with this plan, the issue will be escalated to a convened IRB meeting, with notification to the Institutional Official (IO) if necessary.

When the IRB determines that noncompliance has occurred and that the noncompliance meets the definition of serious or continuing noncompliance, they may:

1 Require submission of a corrective action plan from the PI;

2 Require re-training in human subject protections;

3 Direct that a for-cause (directed) audit be conducted of all the PI’s research activities, and/or;

4 Notification of appropriate institutional officials in cases where other University policies may have been violated (e.g scholarly misconduct, financial disclosure/COI, etc.);

5 Increase in data and safety monitoring of the research activity;

6 Request a status report after each subject receives intervention

7 Modify the study’s continuing review cycle;

8 Notify current subjects, if the information about the non-compliance might affect their willingness to continue participation;

9 Require modification of the protocol;

10 Require modification of the information disclosed during the consent process;

11 Require current subjects to re-consent to participation;

12 Suspend the study (See below); or

13 Terminate the study (See below)

When the IRB identifies a noncompliance event that qualifies as an unanticipated problem posing risks to subjects or others, the established policy and procedure for reviewing such incidents will be implemented The investigator will receive a written notification regarding the IRB's determination and the rationale behind it.

11 Reporting to Regulatory Agencies and Institutional Officials

Policy

Federal regulations require prompt reporting to appropriate institutional officials, and the department or agency head of (i) any unanticipated problems involving risks to subjects or

On March 19, 2020, Stony Brook University’s Human Research Protection Program (HRPP) outlined its commitment to addressing serious noncompliance with policy and IRB requirements, including any suspension or termination of IRB approval The following procedures detail the handling of such reports to ensure compliance and maintain research integrity.

Procedures

The IRB staff will promptly inform the Institutional Official (IO) of any 'reportable' determinations made by the IRBs, including unanticipated problems that pose risks to subjects or others, serious or ongoing non-compliance issues, as well as suspensions and terminations, shortly after the relevant meeting.

2 The IO or designee is responsible for preparing reports or letters which includes the following information:

 The nature of the event (unanticipated problem involving risks to subjects or others, serious or continuing non-compliance, suspension or termination of approval of research);

 Title of the research project and/or grant proposal in which the problem occurred;

 Name of the principal investigator on the protocol;

 Number of the research project assigned by the IRB and the number of any applicable federal award(s) (grant, contract, or cooperative agreement);

 A detailed description of the problem including the findings of the organization and the reasons for the IRB’s decision;

The institution is implementing several measures to address the issue, including revising the protocol, suspending subject enrollment, and potentially terminating the research Additionally, steps will be taken to update the informed consent document, inform currently enrolled subjects, and enhance monitoring of participants to ensure their safety and compliance with ethical standards.

A follow-up or final report will be provided by the earliest of either a specified date or upon the completion of the investigation and implementation of a corrective action plan.

3 The IO is the signatory for all correspondence from the University

4 The IO or designee sends a copy of the report to the following federal agencies:

 OHRP, if the study is subject to DHHS regulations or subject to a DHHS federalwide assurance

When a study is conducted or supported by a Common Rule agency other than the Department of Health and Human Services (DHHS), the report must be submitted to the Office for Human Research Protections (OHRP) or the head of the respective federal agency, in accordance with the agency's requirements.

If a study is conducted or funded by a federal agency that does not follow the Common Rule, any required reports will be submitted to the designated party specified by that agency.

 FDA, if the study is subject to FDA regulations

 Others as deemed appropriate by the IO

Reports are not submitted to federal departments or agencies such as OHRP or FDA unless the research is subject to federal regulations or another mandate that necessitates such reporting

Reporting to a regulatory agency is unnecessary if the event took place at a location not directly overseen by the organization, provided that the agency has already been informed of the incident by another party, such as the sponsor.

SBU’s Human Research Protection Program is accredited by the Association for the

The Accreditation of Human Research Protection Programs (AAHRPP) mandates that organizations report specific incidents promptly, typically within 48 hours, once they or their researchers become aware of them This requirement supplements the routine information provided to AAHRPP in annual reports and re-accreditation applications, ensuring timely communication of critical developments.

 Any negative actions by a government oversight office, including, but not limited to, OHRP

Determination Letters, FDA Warning Letters, and FDA 483 Inspection Reports highlight official actions and compliance measures taken regarding human research protections Additionally, FDA restrictions imposed on Institutional Review Boards (IRBs) or investigators, along with related compliance actions from non-US authorities, underscore the importance of adhering to regulatory standards in human subject research.

 Any litigation, arbitration, or settlements initiated related to human research protections; and/or

 Any press coverage (including but not limited to radio, TV, newspaper, online publications) of a negative nature regarding SBU's HRPP

The Associate Vice President for Research Compliance is tasked with submitting reports to AAHRPP and notifying relevant organizational officials It is the duty of investigators, research staff, HRPP/IRB personnel, IRB members, and other officials, including the Institutional Official and legal counsel, to promptly inform the Office of Research Compliance (ORC) upon discovering any pertinent information, ensuring that reporting obligations are met efficiently.

The AVP-RC, on behalf of the IO ensures that all steps of this policy are completed within thirty

(30) days of the convened IRB’s determination of an unanticipated problem, serious or continuing noncompliance, suspension, or termination

Policy

Principal Investigators (PIs) hold the primary responsibility for ensuring ethical and compliant research conduct While PIs can delegate certain research tasks to study team members based on specific licensure or training requirements—such as venipuncture or medication administration—they must maintain oversight and remain ultimately accountable for the actions of those they delegate responsibilities to.

The following procedures describe the investigator responsibilities in the conduct of research involving human subjects.

Investigators

Only individuals with a current faculty appointment are eligible to be the Principal Investigator (PI) on research projects involving human subjects However, the Institutional Review Board (IRB) may allow University staff to serve as PIs on a case-by-case basis, considering various criteria.

 The individual is not a student;

 Nature of the study; study must be deemed minimal risk to human subjects;

 The individual's training in conducting research involving human subjects;

 The individual's experience in conducting research involving human subjects;

 The individual’s education level, masters or doctorate preferred;

 The individual’s motivation in performing research (e.g must not be doing the research toward a degree or certification);

 Approval and signatory certification of, and oversight by their supervisor

Individuals seeking a waiver from the faculty PI requirement must meet all specified criteria, submit a resume or CV, and send their application to the ORC for IRB review It is essential that these applicants are currently employed at Stony Brook University.

The IRB recognizes one PI for each study The PI has ultimate responsibility for the research activities

Protocols that require skills beyond those held by the PI must be modified to meet the investigator's skills or have one or more additional qualified faculty as co-investigator(s)

Students may not serve as PIs They must have a faculty sponsor who fulfills the PI eligibility criteria and who will serve as PI and faculty advisor on the study

The research team is comprised of members who directly engage with subjects, including tasks such as recruitment and obtaining consent, as well as those who analyze data and tissue samples derived from humans for the specific activity at hand.

Responsibilities

In order to satisfy the requirements of this policy, investigators who conduct research involving human subjects must:

1 Develop and conduct research that is in accordance with the ethical principles in the

2 Develop a research plan that is scientifically sound and minimizes risk to the subjects;

To effectively protect human subjects in research, it is essential to ensure access to a suitable population for recruitment, allocate sufficient time for the study's completion, and employ an adequate number of qualified staff Additionally, the research must be conducted in appropriate facilities, with a clear process in place to inform all team members about the protocol and their specific roles Finally, it is crucial to provide access to necessary medical or psychological resources for subjects that may arise as a result of the research.

Ensure that all study procedures are conducted under proper supervision and carried out solely by licensed or qualified individuals in accordance with New York laws and SBU policies.

5 Assure that all key personnel are educated in the regulatory requirements regarding the conduct of research and the ethical principles upon which they are based;

6 Protect the rights and welfare of prospective subjects;

To minimize risks to subjects, it is essential to employ research procedures that align with sound design principles, ensuring that participants are not subjected to unnecessary risks Additionally, whenever possible, utilize existing diagnostic or treatment procedures already being conducted on the subjects.

8 Recruit subjects in a fair and equitable manner;

9 Obtain and document informed consent as required by the IRB and ensure that no research procedure is performed prior to obtaining and documenting consent from the human subject.;

10 Have plans to monitor the data collected for the safety of research subjects;

11 Protect the privacy of subjects and maintain the confidentiality of data;

When conducting research involving vulnerable populations—such as children, prisoners, pregnant women, individuals with mental disabilities, or those who are economically or educationally disadvantaged—it's essential to implement extra safeguards These measures are crucial to protect the rights and welfare of these subjects, ensuring ethical standards are upheld throughout the study.

13 Have a procedure to receive complaints or requests for additional information from subjects and respond appropriately;

14 Ensure that pertinent laws, regulations, and institutional procedures and guidelines are observed by participating investigators and research staff;

15 Ensure that all research involving human subjects receives IRB review and approval in writing before beginning the research;

16 Comply with all the IRB decisions, conditions, and requirements;

17 Ensure that protocols receive timely continuing IRB review and approval (as applicable);

18 Report deviations, noncompliance, and unanticipated problems involving risks to subjects or others in accordance with these SOPs;

Before making any changes to approved protocols or consent forms, ensure that you obtain written approval from the IRB, except in cases where modifications are required to address immediate hazards to the subjects.

20 Seek IRB assistance when in doubt about whether proposed research requires the IRB review.

Training/ Ongoing Education of Investigators and Research Team

A key element of a robust human research protection program is the education and training of all individuals involved with human subjects The University is dedicated to offering ongoing training for investigators and their research teams, focusing on ethical considerations and regulatory requirements for safeguarding human subjects For instance, initial and continuous research ethics education is mandatory for all personnel engaged in human subjects research sponsored by the Department of Defense.

Approval for new and continuing review submissions will be delayed if any individuals listed on the electronic submission form as part of the study team lack current certification for conducting human subject research The Office of Research Compliance (ORC) oversees the database of training certifications.

All PIs and members of their research team must:

Review essential training materials such as the "SBU Standard Operating Policies and Procedures for Human Research Protection" and the "Belmont Report," which outlines ethical principles and guidelines for safeguarding human subjects in research.

 Be familiar with the University HRPP website, and the availability of links and other information contained within;

 Complete the University-required Basic Modules in the CITI Course in the Protection of Human Research Subjects, and pass the required quizzes with a score of 80 or better

Refresher training must be completed every 3 years

Study Coordinators registered with the Office of Clinical Trials are required to complete the CITI course on Clinical Research Coordinators (CRC) once Additionally, NIH-funded investigators and clinical trial site staff overseeing NIH-funded clinical trials must undergo Good Clinical Practice (GCP) training every three years.

12.4.1.1 The Collaborative Institutional Training Initiative (CITI)

The University provides access to the CITI program for all faculty, staff, and students Non-University investigators may also utilize the CITI program if they are registered with the IRB as an investigator on an approved or pending IRB application However, unauthorized use of the CITI program is strictly prohibited.

The CITI web-based program can be accessed at http://www.citiprogram.org, where investigators can register under SUNY University at Stony Brook Upon logging in, users will answer questions to determine the necessary training based on specific criteria, making it the investigator's responsibility to select the answers that best reflect their situation.

 Level of University training (initial, refresher);

 Type of research (biomedical, social behavioral); and

 Role in the research activities (data/tissues only, interaction with subjects, etc.)

Completion of the initial training through CITI takes approximately four to six (4-6) hours, although the trainee can go back over multiple sessions to complete training

The Biomedical Research Alliance of New York (BRANY), which offers IT and administrative support along with hosting the CITI Program, provides CME/CEU credits for a fee To earn these credits, participants must complete and pass all required modules for their selected group For more detailed information, please click the CME/CEU credits link in the Learner's Menu.

New investigators or research team members who have completed equivalent CITI training at their previous institution may request a waiver for Initial Education requirements at the University However, they must still review the "SBU Standard Operating Policies and Procedures for Human Research Protection" and associated website materials.

All researchers and their teams are required to fulfill the University’s continuing education mandate every three years following their initial certification, as long as they are engaged in human subject research This requirement is mandatory and applies without exception.

 The University required CITI Refresher Modules (chosen in accordance with the criteria referenced above in Section 12.4.1.1), with a passing score on the required quizzes with a score of 80 or better

The ORC offers a refresher course in human research protections for groups of twenty or more trainees, which includes a requirement to complete a modified CITI refresher course To demonstrate competency in the course material, participants must achieve a score of 80 or higher on the necessary quizzes.

Stay informed with the latest HRPP updates, reminders, guidance, and hot topics shared regularly through emails from the ORC and the Vice President for Research's quarterly 'Research News' These resources are essential for keeping the campus community updated on important developments in human research protections.

 Attendance at PRIM&R or OHRP seminars, conferences and webinars, and/or attendance at an ORC sponsored workshop, and/or

 Required training for investigators who are also IRB Chair, IRB members, or ORC staff

(described in this policy under Section 2.13)

The ORC website will provide ongoing access to human research protection information, along with regular updates from the IRB This initiative aims to keep the University research community informed about current regulatory requirements, policy changes, and available training opportunities.

Investigator Concerns

If investigators have concerns or suggestions about the University’s human research protection program, they should reach out to the AVP-RC, the IO, or relevant authorities such as the college dean or departmental chair The AVP-RC will investigate the issue and, if necessary, bring together the involved parties to formulate a response or implement required changes to procedures or policies.

D a t e : 3 / 1 9 / 2 0 2 0 warranted In addition, the IRB Chair, AVP-RC, or the IO will be available to address investigators’ questions, concerns and suggestions.

Investigator Disclosures of Significant Financial Interest

Investigators at the University must maintain a clear distinction between their responsibilities and personal financial interests It is essential to safeguard public funds and ensure that University research, education, and public service remain uncompromised by any private obligations of investigators.

Investigators will follow these SOPs located at Section 14, which set forth requirements and guidelines for:

 Disclosure of outside interests by investigators at the University who engage in University activities funded by specified internal and external entities;

 Review of investigator disclosures by University officials; and

 Identifying, reporting and managing conflicts of interest

Policy

It is University policy that any sponsored research conducted under the auspices of the

University is conducted in accordance with federal guidelines and ethical standards

The following describe the procedures required to ensure that all sponsored research meets this requirement.

Definitions

Sponsor: The company, institution, individual donor, or organization responsible for the initiation, management or financing of a research study.

Responsibility

All sponsor contracts for research involving human subjects undergo a thorough review by the Office of Sponsored Programs (OSP) To maintain consistency across each sponsored protocol, the Office of Research Compliance collaborates with OSP to share essential contract and study information Furthermore, OSP evaluates sponsor contracts to ensure compliance with relevant standards.

1 All sponsor contracts will indicate that the University will follow the protocol, applicable regulations and its ethical standards;

2 All sponsor contracts will define who will be responsible for research related injuries, where applicable (see section 13.4 below for University policy);

If the sponsor oversees the research, the contract must specify that any findings from the study monitor that could impact participant safety, their willingness to continue, or the study's conduct, as well as any changes to the IRB's approval, must be promptly communicated to the IRB by the sponsor.

4 If the sponsor discovers results that could affect the safety or medical care of subjects, the sponsor will make sure the IRB is notified;

When the sponsor is tasked with data and safety monitoring, the agreement mandates that they submit monitoring reports to the IRB and communicate any findings that could impact participant safety or affect the research's integrity during or after the study's conclusion.

All sponsor contracts will include clauses about the dissemination of research findings, ensuring that the University investigator has the right to publish results However, sponsors may reserve the right to review the findings before publication and, in specific situations, may delay publication for a reasonable duration.

All sponsorship contracts and funding agreements mandate that sponsors must report any findings that may impact subject safety, affect study conduct, or change the IRB's approval status within thirty (30) days.

Policy on Payment of Research-related Injury Costs in Industry-funded and Initiated

The University plays a vital role as a participating site in industry-funded clinical trials, including those initiated by pharmaceutical and device companies This involvement is essential for the evaluation and marketing of innovative investigational drugs, devices, and biologics, as well as new indications for approved products.

Patients play a crucial role in aiding companies to market test products for both public benefit and profit Therefore, it is essential that the costs related to research-related injuries incurred by subjects participating in these trials be covered by the companies involved Subjects should not be held financially responsible, either directly or through their insurance, for any expenses arising from research-related injuries in industry-sponsored clinical trials.

This policy is not intended to waive any of a research subject’s legal rights; or release the investigator, the sponsor, the University or its agents from liability for negligence

Waivers of this policy will be considered on a case by case basis by the AVP-RC, the IO, and other University Officials as deemed necessary

Research-related injuries refer to harm that occurs directly from the test product or from correctly executed study procedures These injuries do not encompass the natural progression of a participant's existing disease or injuries arising from interventions that would have taken place regardless of the subject's involvement in the clinical trial.

14 Conflict of Interest in Research

Policy

Investigators at the University must maintain a clear distinction between their responsibilities to the institution and their personal financial interests or obligations It is essential to ensure that public funds are managed wisely, safeguarding the integrity of University research, education, and public service from potential conflicts arising from private interests.

This policy sets forth requirements and guidelines for:

 Disclosure of outside interests by investigators at the University who engage in University activities funded by specified internal and external entities;

 Review of investigator disclosures by University officials; and

 Identifying, reporting and managing conflicts of interest.

Definitions

A conflict of interest arises when an investigator has the potential to influence decisions or activities related to externally or internally supported projects, which could result in personal financial benefits for themselves or their immediate family members This situation may also provide unfair advantages to third parties in their interactions with the University.

Conflicts of interest can occur when Investigators or their Immediate Family Members have external commitments that significantly clash with the Investigator's responsibilities to the University or the public interest.

The Designated Institutional Official (DIO) is tasked with soliciting and reviewing certifications from investigators while also creating management plans to address financial conflicts of interest or significant obligations Appointed by the Vice President for Research (VPR), the DIO plays a crucial role in ensuring compliance and serves as the final decision-maker in the appeals process.

A Financial Conflict of Interest (FCOI) arises when a Significant Financial Interest (SFI) is linked to activities that could directly or significantly impact their design, conduct, or reporting The Determining Institutional Official (DIO) is responsible for assessing whether an SFI qualifies as a FCOI This evaluation is particularly critical when the activities involve human subjects.

OHRP and/or FDA as applicable, the IRB will also make an independent decision regarding the presence of a FCOI

1 Any remuneration to the Investigator (and/or those of the Investigator’s Immediate Family Member) from outside the University, and/or

2 Any equity holdings or ownerships of the Investigator (and/or those of the Investigator’s Immediate Family Member), and/or

3 Intellectual property rights and interests (e.g., new technology disclosures, patents, copyrights) where a company has entered into an option to license, or license, such rights and interests from the University

4 Intellectual property rights and interests upon receipt of income related to such rights and interests

Note: All royalties, including those received by the Investigator from this University, are to be disclosed

 Income from investment vehicles, such as mutual funds and retirement accounts, as long as the Investigator does not directly control the investment decisions made in these vehicles;

Income generated from seminars, lectures, or teaching engagements sponsored by federal, state, or local government agencies, as well as institutions of higher education, academic teaching hospitals, medical centers, or research institutes affiliated with such educational institutions, is included in this context.

 Income from service on advisory committees or review panels for a federal, state or a local government agency, a (United States) institution of higher education as defined at 20 U.S.C

1001 (a), an academic teaching hospital, a medical center, or a research institute that is affiliated with an institution of higher education

Institutional responsibilities encompass all professional duties and activities that an investigator is contracted to undertake at the University, for which they receive compensation These responsibilities include, but are not limited to, conducting research, providing research consultation, teaching, engaging in professional practice, serving on institutional committees, and participating in panels like Institutional Review Boards or Data and Safety Monitoring Boards.

Investigator (specific to IRB submissions only): All study team members listed in the electronic management system for a project submitted to the IRB For the purposes of this policy,

"investigator" shall include the investigator's spouse and all dependent children

Obligation: An unpaid position - held as an officer, trustee, director, adjunct professor, advisor, scientific advisor, board member or consultant of a for-profit or not-for-profit entity

Significant Financial Interest (SFI) refers to financial interests of the Investigator or their Immediate Family Members that are reasonably related to the Investigator's Institutional Responsibilities.

A publicly traded entity is defined as one where the total value of any remuneration received in the twelve months prior to disclosure, combined with the value of any equity interest held in the entity at the time of disclosure, exceeds $5,000.

A non-publicly traded entity is defined by the total remuneration received, which must exceed $5,000 within the twelve months prior to disclosure Additionally, this definition includes instances where the investigator or their immediate family member holds any equity interest in the entity.

Intellectual property encompasses rights and interests such as patents and copyrights, along with the associated royalties and agreements for sharing these royalties At SBU, it is mandatory to disclose all royalties, including those received by investigators from the University.

Investigators at PHS/NIH must disclose any reimbursed or sponsored travel related to their Institutional Responsibilities that exceeds $5,000 from a single entity within the past 12 months This disclosure should include details such as the sponsor, destination, duration, and purpose of the travel However, travel funded by federal, state, or local government agencies, institutions of higher education, academic teaching hospitals, medical centers, or research institutes affiliated with higher education is exempt from this requirement.

Significant Obligations (SO): Significant Obligations (SO) includes obligations that would reasonably appear to be related to an investigator’s institutional responsibilities.

Procedures for Financial Disclosure

In research involving human subjects, the Designated Institutional Official (DIO) and the Institutional Review Board (IRB) are responsible for reviewing financial disclosures from investigators and developing conflict management plans Additionally, the IRB staff collaborates closely with the DIO, while the Assistant Vice President for Research Compliance (AVP-RC) holds a non-voting ex officio position on the Conflict of Interest (COI) Committee.

The University Policy P209 outlines the Investigator Conflict of Interest Policy, detailing the requirements for certification submissions and reviews It specifies how to determine when significant financial interests or obligations may lead to conflicts of interest, the creation of conflict management plans, and the necessary reporting requirements.

In human subjects research, the QA Administrator in ORC informs the DIO about all funded studies submitted to the IRB The DIO assesses whether any investigator listed in the submission has a Significant Financial Interest (SFI) or Significant Outside Interest (SO) These instances are then reviewed by the full committee to evaluate potential conflicts and management plans, ensuring the protection of human subjects involved in the research.

If any of the Investigators on the protocol have an FCOI or SO the IRB requires (where it is determined that the conflict can, in fact, be managed) that:

The DIO must provide a written confirmation indicating that the conflict of interest can be effectively managed, along with a proposed management plan The IRB will then review this plan and has the authority to modify or enhance it as necessary In cases of any discrepancies or disagreements, the IRB's decision will take precedence over that of the DIO.

The Investigator must not participate in recruiting or consenting subjects, and this limitation should be clearly stated in the consent documents If the Investigator is listed as not involved in these processes, any discussions regarding the research protocol must be handled by an IRB-approved co-investigator If the Investigator is also the patient's treating physician, they can inform the patient about standard therapies and available research studies Should the patient express interest in learning more about research options, a referral to the IRB-approved co-investigator is required.

 The Investigator cannot place undue pressure on, or offer incentives to, other investigators to enroll subjects

The consent form must include a section titled "Notice of Investigator Conflict of Interest," which identifies the investigator(s) with a Financial Conflict of Interest (FCOI) or Significant Other (SO) This section should explain, in simple terms, the nature of the FCOI or SO and clarify that the named investigator(s) will not participate in the recruitment or consenting of study subjects Additionally, it should outline any other necessary components of a management plan as mandated by the Institutional Review Board (IRB).

 As with any study, the consent processes for any or all subjects may be witnessed by an IRB or ORC representative

Clinical studies that utilize investigational human drugs, biological products, or medical devices must adhere to specific certifications and disclosure requirements outlined in the FDA regulations, specifically Title 21 CFR Part 54.

Institutional Conflict of Interest

As an organization that conducts and reviews research involving human subjects, the University recognizes its obligation to protect the rights and welfare of those subjects, and ensure the

On March 19, 2020, it is crucial to uphold the integrity of research and the human research protection program To achieve this, it is essential to identify, evaluate, manage, and minimize or eliminate any financial interests held by the University or senior administrative officials at both campus and central levels, ensuring that these interests do not compromise our obligations.

14.4.1 Definition of Institutional Financial Conflicts of Interest

An "Institutional Financial Conflict of Interest" in human subjects' research occurs when Stony Brook University's financial interests could influence or appear to influence various aspects of the research process, including its design, conduct, reporting, review, or oversight These conflicts are particularly concerning as they may compromise the integrity of the research and the safety of the participants involved To address these potential conflicts, all forms must be disclosed, evaluated, and either managed or eliminated in accordance with established policies.

An “Institutional Financial Conflict of Interest” (IFCOI) exists when:

The University is likely to receive royalty income from products associated with any patent, license, or copyright held by SUNY/RF, whether issued or pending, that are intended for use in human subjects' research projects at Stony Brook University.

The University engages in technology licensing activities that may involve holding equity interests in research sponsors of human subjects’ research projects, regardless of whether these sponsors are public or non-public entities.

The University has obtained significant contributions, including in-kind donations, from a prospective commercial sponsor involved in human subject research or from a company that owns or manages products currently being researched or tested on human subjects.

Senior Administrative Officials responsible for human subject research, along with their spouses and dependent children, must adhere to specific criteria These officials may hold positions such as officers, trustees, directors, employees, or consultants in commercial research sponsors or companies that own products under study They may also receive various forms of remuneration from these entities, including salaries, consulting fees, honoraria, or payments for services not classified as salary Additionally, they might possess equity interests, such as stocks or stock options, in the commercial research sponsors or companies involved in the research of human subjects.

D a t e : 3 / 1 9 / 2 0 2 0 d Holds intellectual property rights and interests (e.g., patents, copyrights), royalties from such rights, etc relating to products being studied or tested in a human subject

The following offices report at least semi-annually to the QA Administrator within ORC on interests described above:

1 Technology Licensing and Industry Relations Office: o to report licensing arrangements, patents, invention disclosures;

2 Advancement Office/Stony Brook Foundation o to report gifts

Senior administrative officials are required to disclose their significant financial interests related to human research initially and annually thereafter They must submit a new disclosure form if any details change, which will be reviewed for potential conflicts of interest (ICOI), accompanied by necessary management plans.

 Chairs (of departments identified by Office of Research Compliance [ORC] as conducting human research activities)

IRB proposals submitted to the Office of Research Compliance prior to IRB review will be evaluated by the QA Administrator for potential Investigators' Financial Conflicts of Interest (IFCOI), based on the relevance of information in the associated reports and forms.

The University has a strict policy against participating in human subject research projects when there is an Identified Financial Conflict of Interest (IFCOI) An exception to this policy may only occur if the Institutional Review Board, in consultation with the Conflict of Interest Administrator and/or the Conflict of Interest Committee as outlined in University Policy P209, concludes that participation is justified.

 Circumstances exist to justify SBU’s participation in the project while still maintaining the protection of human subjects, and

 A conflict management plan is adopted to maintain research integrity and serve the best interests of subjects enrolled in the research

These circumstances and conflict management plans will be documented

If the University’s participation in a project is permitted notwithstanding the IFCOI, the

University participation requires an approved conflict management plan by the IRB For senior administrative officials, the conflicted individual must agree to the plan The IRB holds the ultimate authority to assess whether any identified financial conflicts of interest (IFCOI) and their management permit research approval.

Options for managing institutional conflict of interest, include but are not limited to the following:

 Disclosing the institutional conflict of interest to research subjects in the consent process and documents

 Disclosing the institutional conflict of interest to any journals or other publications for which the results of the research will be submitted

 Recusing conflicted senior administrative officials from scientific merit review of human research

 Having an external, independent IRB review the research in question

 Monitoring of research by independent reviewers

 Divestiture of financial conflicts of interests

 Severance of relationships that create actual or potential conflicts

 Prohibiting the conduct of the research at the University

Investigator Conflict of Interest Unrelated to Current Financial Conflict of Interest

In cases where a study team member has a personal interest in the future success of a drug or device being researched, such as involvement in its discovery or patenting, but lacks a significant financial interest that necessitates a conflict of interest review, it is permissible for that investigator to recruit or consent potential subjects However, it is essential to include a specific statement in the consent form addressing this situation.

"Investigator’s Personal Interest in this Study"

Dr , who is one of the investigators conducting this study has a personal commercial interest in, or may financially benefit in the future from, the development of the

[drug, device, etc.] being tested in this study

Policy

The University is dedicated to providing educational opportunities for research subjects, prospective participants, and community members, aimed at improving their understanding of human participation in research activities at SBU.

Research Subject Advocate (RSA)

The Institution demonstrates its dedication to both current and future research subjects by appointing a dedicated ORC IRB staff member to oversee research participant welfare.

Advocate (RSA) This individual will:

 Work within University Hospital to promote educational efforts for patients regarding participation in research, and assist with, and streamline, procedures relating to recruitment of patients into research studies

 Assist patients with navigating the research informed consent process

 Disseminate materials, and organize educational events to train research volunteers, investigators, and staff regarding participant rights and protections

 Serve as institutional liaison for ResearchMatch, the national recruitment registry that matches researchers to individuals who are interested in participating in research (see Section 17.13 for more details on process)

Outreach Resources and Educational Materials

The RSA is enhancing the Human Research website by creating a section titled “Volunteering in Research,” which offers an overview of research volunteering, answers to Frequently Asked Questions (FAQs), and access to institutional brochures This section also features links to the Office for Human Research Protections (OHRP) to educate the public about research participation, aiming to raise awareness and highlight the critical role individuals play in advancing scientific knowledge.

The RSA participates in outreach activities (e.g., presence at health fairs, at University Hospital etc.) for community education efforts

Evaluation

The RSA regularly assesses its outreach activities and makes necessary adjustments through informal, ongoing evaluations Effectiveness is gauged by analyzing website traffic following various initiatives These assessments and subsequent revisions to the outreach program are documented, and the RSA meets periodically with the AVP-RC to update on the program's effectiveness and discuss future activities and resource needs.

16 Health Insurance Portability and Accountability Act (HIPAA)

Policy

Protected Health Information (PHI) acquired by the University is strictly prohibited from internal use or external disclosure for research purposes without prior approval from the Institutional Review Board (IRB) and adherence to relevant HIPAA privacy and security policies, in line with the University’s designation as a ‘hybrid’ covered entity.

The following describe the procedures for conducting research at the University in accordance with the Health Insurance Portability and Accountability Act (HIPAA) of 1996.

Definitions

Access: The mechanism of obtaining or using information electronically, on paper, or other medium for the purpose of performing an official function

Authorization is a comprehensive document that grants covered entities the right to utilize protected health information for specific purposes beyond treatment, payment, or healthcare operations It also allows for the disclosure of this information to a designated third party as specified by the individual.

Covered entity: The term applied to institutions that must comply with the Privacy Rule These include:

Health care providers engaging in specific financial and administrative transactions electronically must adhere to standards established by the Secretary under HIPAA This includes processes like electronic billing and fund transfers, ensuring compliance and efficiency in health care operations.

Common Rule: A federal policy on human subject protection that provides for the primary source of regulation of research

De-identified information refers to health data that cannot be linked to an individual, meaning there is no reasonable basis for identifying someone from that data Once information is de-identified, it is no longer governed by the Privacy Rule and is exempt from HIPAA regulations.

Deletion: The removal, erasing, or expunging information or data from a record

Disclosure: The release, transfer, provision of access to, or divulging in any other manner information outside of the covered entity

Health information encompasses any data generated or obtained by healthcare providers or health plans that pertains to an individual's past, present, or future physical or mental health status This includes details about the delivery of healthcare services to the individual and the financial transactions related to those services.

Individually Identifiable Health Information (IIHI): A subset of health information, including demographic information collected from an individual that identifies the individual (either directly, or through codes/identifiers)

A Limited Data Set refers to protected health information that omits certain direct identifiers related to individuals or their relatives, employees, or household members This type of data can solely be utilized for research, public health initiatives, or healthcare operations, and may be disclosed specifically for research purposes.

Minimum Necessary: The principle that any access should be limited to the minimum amount of information needed to accomplish the intended purpose of the use or disclosure

The Privacy Board refers to a group of individuals with diverse backgrounds and relevant professional expertise, tasked with reviewing and safeguarding individual privacy rights At the University, this role is fulfilled by the Institutional Review Board (IRB), which acts as the designated privacy board.

The Privacy Act safeguards the confidentiality of personally identifiable information about living individuals stored in record systems, allowing disclosure only when explicitly permitted by law It ensures that the collection of personal data is restricted to what is legally authorized, relevant, and necessary.

The Privacy Rule offers essential guidelines for handling protected health information in research, imposing specific requirements on researchers and institutions It emphasizes the importance of individual privacy, allowing people to control access to their personal information Evaluating privacy involves assessing how investigators will obtain information about subjects, and Institutional Review Board (IRB) members must implement strategies to safeguard privacy during interactions with potential subjects and when accessing sensitive data.

Protected Health Information (PHI) refers to any health-related data that can identify an individual and is stored or shared electronically or in any format, excluding education and employment records as specified in the Privacy Rule.

Preparatory Research: The method applied to developing or designing a research study

Waiver of Authorization: A means of requesting approval from the IRB (as the Privacy Board) rather than asking each research subject for an authorization to access protected health information.

Historical Background

The Health Insurance Portability and Accountability Act of 1996 (HIPAA) established a Privacy Rule to protect identifiable health information This Privacy Rule primarily influences the routine delivery and billing of healthcare services, but it also significantly impacts research practices Therefore, it is essential for investigators, Institutional Review Board (IRB) staff, IRB members, and research administration to be knowledgeable about these regulations.

Research under HIPAA

HIPAA defines research as a systematic investigation that encompasses research development, testing, and evaluation aimed at generating or enhancing generalizable knowledge, a definition that aligns with the one established in the “Common Rule.”

16.4.1 Effects of HIPAA on Research

The Privacy Rule maintains the integrity of the Common Rule while incorporating several similar provisions and referencing them.

The University operates as a hybrid covered entity under HIPAA, comprising both covered components, such as health care providers in the University Hospital, and non-covered components, including academic departments in the College of Arts and Sciences.

 Where the investigator is also a covered entity, i.e a health care provider, then she/he is legally mandated to comply with all provisions of HIPAA when accessing or generating PHI

 Where the investigator is not a covered entity (i.e not a health care provider), the

University requires that HIPAA procedures be followed as ‘best practices’, as described in this document

In general, the Privacy Rule permits covered entities to use or disclose protected health information for research purposes when the individual who is the subject of the information

As of March 19, 2020, the use or disclosure of protected information requires authorization, with exceptions noted below When authorization is necessary, researchers must use a combined authorization and informed consent form, which must be completed and submitted to the Institutional Review Board (IRB) for review and approval.

The Privacy Rule allows covered entities to share protected health information with investigators for "review preparatory to research" without needing authorization This process helps in developing research protocols and assessing the availability of potential research subjects However, before granting access to this information, the Institutional Review Board (IRB) must approve the HIPAA Preparatory to Research Form.

Investigators can include a recruitment plan in their IRB submission that facilitates preparatory research activities This plan must ensure that the health care providers of identified patients are part of SBU’s HIPAA-covered entity.

Organized Health Care Arrangements (OHCA) involve the distribution of information sheets, which must be submitted and approved by the Institutional Review Board (IRB) These sheets can be provided to healthcare providers for distribution to eligible patients, ensuring they have access to important information Additionally, these sheets will include the researcher's contact details for patients seeking further information.

16.4.3 Use and/or Disclosure of De-identified Health Information: NOT subject to HIPAA

Where the investigator proposes use of PHI from which the following 18 identifiers are removed, HIPAA does not apply to the research:

 Address (street address, city, county, zip code -with certain exceptions),

 Dates (e.g birth date, admission date, discharge date, date of death) and individual ages if over 89,

 Vin and serial numbers, license plate numbers

 Device identifiers and serial numbers,

 Web Universal Resource Locators (URL's),

 Internet Protocol (IP) address numbers,

 Biometric identifiers (including finger and voice prints),

 Full face photographic images and any comparable images, and

 Any other unique identifying number, characteristic, or code

Before initiating any proposed activity, it is essential to obtain approval from the Institutional Review Board (IRB), even though HIPAA regulations do not apply Additionally, a HIPAA De-Identification Form must be submitted alongside the standard IRB submission documents.

16.4.4 Research on Protected Health Information of Decedents

The Common Rule protects only living individuals, while the Privacy Rule extends its protections to the identifiable health information of deceased persons Notably, the Privacy Rule allows for the use or disclosure of decedents' protected health information for research purposes without requiring authorization, provided that investigators confirm the use is solely for research on decedents and that the information is essential for the study Additionally, investigators may need to provide documentation of the individuals' deaths when requested by the covered entity To initiate research involving decedents' protected health information, investigators should submit the CORIHS HIPAA Research on Decedent PHI Form for IRB review and approval.

16.4.5 Limited Data Sets with a Data Use Agreement

Under the Privacy Rule, investigators can access a "Limited Data Set" without patient authorization when specific data elements are needed, as long as they sign a Data Use Agreement While this limited data set is still classified as protected health information, it must exclude 16 specific identifiers.

 Postal address info (if other than city, state and zip),

 Vin and serial numbers, license plate numbers,

 Biometric identifiers (finger prints), or

 Full face, comparable photo images

The Privacy Rule requires that the Data Use Agreement used in conjunction with the Limited Data Set contain provisions that:

The recipient of the Limited Data Set must clearly define the allowed uses and disclosures in alignment with the research objectives, ensuring that no actions taken would contravene the regulations applicable to the covered entity.

2 Limit who can use or receive the data; and

The recipient must agree to several key conditions regarding the handling of information: they are prohibited from using or disclosing the information beyond what is allowed by the data use agreement or required by law Additionally, they must implement appropriate safeguards to protect the information and promptly report any unauthorized use or disclosure to the covered entity It is also essential that any agents or subcontractors receiving the Limited Data Set adhere to the same restrictions, and the recipient must ensure that the information remains anonymous, avoiding any identification or contact with individuals.

Investigators who will be receiving a Limited Data Set must submit a signed copy of the covered entity’s Data Use Agreement to the IRB for approval, prior to initiating the research

16.4.6 Waiver of Authorization for Use or Disclosure of Protected Health Information in Research

Under the Privacy Rule, covered entities can use and disclose protected health information for research purposes either with individual authorization or, in certain limited cases, without it Specifically, a covered entity may proceed with research without individual authorization if they have documentation that the Institutional Review Board (IRB) has granted a waiver This provision allows for various types of research, such as records research and epidemiological studies, particularly when de-identified data is not available or appropriate for the research objectives.

The waiver documentation presented to the covered entity must include the following:

1 Identification of the IRB and the date on which the alteration or waiver of authorization was approved;

2 A statement that the IRB has determined that the alteration or waiver of authorization, in whole or in part, satisfies the three criteria in the Rule;

3 A brief description of the protected health information for which use or access has been determined to be necessary by the IRB;

4 A statement that the alteration or waiver of authorization has been reviewed and approved under either normal or expedited review procedures; and

5 The e-signature of the IRB Chair or other IRB member, as designated by the IRB Chair

The following criteria must be satisfied for the IRB to approve a waiver of authorization under the Privacy Rule:

The use or disclosure of protected health information poses minimal risk to individuals' privacy when certain key elements are present.

1 An adequate plan to protect the identifiers from improper use and disclosure;

To ensure compliance with research protocols, it is essential to implement a timely plan for the destruction of identifiers, unless retention is justified for health or research purposes, or mandated by legal requirements.

HIPAA and Documentation Requirements

Where health information is proposed for use or disclosure in a research activity, applicable HIPAA documents must be included with the IRB submission, e.g.:

 HIPAA Waiver of Authorization Form,

 HIPAA Limited Data Set Form,

 HIPAA Research on Decedents Form,

 HIPAA Preparatory to Research Form, or

For investigators using University Hospital facilities and/or patients, the ‘Application for

Approval to Conduct Research Activities at Stony Brook University Hospital Inpatient or

Outpatient Facilities’ (available in the electronic management system’s forms library) must be uploaded, and the HIPAA Privacy Officer must e-certify to approve data disclosure to the study sponsor

Quality Assurance/ Quality Improvement (QA/QI) Activities vs Research Activities

Quality Assurance (QA) and Quality Improvement (QI) initiatives are essential functions at Stony Brook University Medical Center, aimed at enhancing patient care and safety These initiatives are implemented based on evidence-based best practices, addressing identified safety concerns, and striving to improve overall care delivery The primary goal is to ensure continuous monitoring of hospital operations, ultimately leading to better patient outcomes.

The "Application for Designation of Activity as Quality Assurance/Quality Improvement or Research" can be found in the electronic management system's Forms and Documents Library, providing essential support for investigators in accurately designating their activities related to QA/QI initiatives.

At the University, certain activities are classified as non-research activities, which are governed by the SBUMC’s Division of Medical and Regulatory Affairs and recognized departmental quality assurance committees, collectively known as ‘Hospital QA’.

SBUMC's hospital quality assurance initiatives focus on measuring and enhancing its ability to meet or surpass national care standards, such as those set by the Joint Commission Additionally, these initiatives aim to establish care standards tailored for SBUMC The data gathered from these efforts is submitted to national or state registries and databases to ensure compliance and improvement in healthcare quality.

 That is mandated at the state or federal level, OR

Reimbursements and funding from state agencies, the Department of Health, and the federal Centers for Medicare & Medicaid Services (CMS) are directly influenced by performance and clinical or quality outcomes.

The organization or consortium, officially acknowledged by SBUMC’s Division of Medical and Regulatory Affairs, primarily focuses on benchmarking and performance improvement, serving as a resource for internal activities within the University.

Hospital Quality Assurance (QA) utilizes data from registries or databases to enhance the Strategic Business Unit's (SBU) capacity to meet or surpass established national care standards, such as those set by JCAHO Additionally, this data is instrumental in formulating care standards or benchmarks specifically applicable within SBUMC.

The following activities are considered research activities The responsible conduct of the activities below fall under the jurisdiction of ORC and/or Institutional Review Board (IRB):

The hospital's Quality Assurance (QA) initiative at SBUMC aims to establish a standardized care framework that is applicable not only within its operations but also extends to external organizations, promoting best practices in healthcare delivery.

Any quality assurance (QA) or quality improvement (QI) initiatives, particularly those aimed at establishing operational care standards or benchmarks, must be investigator-initiated These initiatives require proper vetting and endorsement from SBUMC’s Division of Medical and Regulatory Affairs or a recognized departmental QA committee within the hospital.

 Submission of data to a registry/database that is not covered by those described above

Utilizing data from any registry or database to measure, enhance, or establish a standard or benchmark is permissible under conditions not previously outlined, including the application of registry data for research purposes.

Any activity that involves comparing one or more interventions, which are intentionally provided to certain patients or hospitals through randomization or other methods, is included in this definition However, this does not apply to the initiation of a quality improvement (QI) process in a limited number of patients at SBUMC to assess feasibility prior to a broader implementation across the entire patient population.

17.1.2 Activities that have a mix of both QA/QI and Research Components

When engaging in activities that encompass elements from both Sections A and B, it is essential to comply with the relevant authority, specifically SBUMC’s Division of Medical and Regulatory Affairs for Quality Assurance/Quality Improvement (QA/QI) aspects, and the ORC Institutional Review Board (IRB) for research components This includes obtaining necessary approvals before initiating any research activities.

For any ‘questionable’ (QA vs Research) activity not described above, please consult with the

ORC and/or the Division of Medical and Regulatory Affairs for assistance

Data/ Tissue Registries/ Banks

Mandated registries and biobanks are those:

 That are required by a state or federal agency, or

Reimbursement and funding from state agencies, the Department of Health, and the federal Centers for Medicare & Medicaid Services (CMS) are significantly influenced by performance metrics and clinical or quality outcomes.

To comply with Joint Commission and other established standards, it is essential for SBU's University Hospital (SBUH), its departments, and the SBU Clinical Practice Management Plan (CPMP) to adhere to specific requirements regarding treatment, payment, and operational procedures.

Research involving identifiable data or specimens from registries or biobanks is not governed by IRB jurisdiction; however, any proposed studies utilizing this data must receive prior review and approval or exemption from an SBU IRB.

17.2.2 Non-Mandated Registries and Biobanks:

Non-mandated registries and biobanks are those that are not listed above as mandatory IRB oversight is dependent on the intent of the registry or biobank

If a registry or biobank is established solely for SBU-recognized quality assurance activities, it is exempt from IRB jurisdiction However, the initiation of data or tissue use from the registry or biobank for quality assurance purposes requires prior written approval from the appropriate authority, as outlined in Section 17.1 regarding QA activities at the University.

To bank data or tissue for future research activities, both the registry or biobank and the individual research projects must obtain Institutional Review Board (IRB) approval This ensures that all aspects of the registry or biobank's creation, as well as any subsequent research utilizing the stored data or tissue, comply with ethical standards and regulatory requirements.

Informed consent is essential for patients whose data or tissue is stored in a non-mandated registry or biobank Patients must clearly understand that their consent pertains solely to the banking process Furthermore, it should be explicitly stated that any future research utilizing their data or tissue will undergo an ethics review to assess the ethical and scientific validity of the proposed studies.

 HIPAA Authorization: Patients must provide HIPAA authorization for their data and/or tissue to be banked in a non-mandated, non-QA registry/biobank

(https://grants.nih.gov/grants/policy/coc/index.htm) should be obtained for each registry and biobank to protect the confidentiality of the stored data and tissues

 Licensure: Biobanks must operate under appropriate licensure from the NYS Department of Health; See section 17.2.3 below for more information

Stony Brook University operates a licensed BioBank, currently under the oversight of Dr

Kenneth Shroyer, Chair of Pathology Any biobank that is proposed must be specifically added to the University’s license on file with the NYS Department of Health

International Research

The IRB will review all international research using human subjects to assure adequate provisions are in place to protect the rights and welfare of the subjects

Approval of research is permitted if “the procedures prescribed by the foreign institution afford protections that are at least equivalent to those provided in 45 CFR 46.”

All policies and procedures that are applied to research conducted domestically should be applied to research conducted in other countries, as appropriate

For international research, obtaining approval from local IRBs or ethics committees is essential to ensure a thorough understanding of the local research context This requirement may involve securing local letters of support, depending on the study's nature, the country, and the resources accessible to the principal investigator (PI) When a local IRB or Independent Ethics Committee (IEC) is present, the IRB must review and approve the foreign institution's IRB/IEC assessment before the research can begin at that site.

In international research settings lacking Institutional Review Boards (IRBs), additional verification may be required before research approval This involves gathering insights from individuals familiar with local customs and standards of care, such as local IRBs, ethics committees, or regional experts The Associate Vice President for Research Compliance (AVP-RC), representing the Institutional Official (IO), will evaluate transnational research proposals to ascertain if the IRB possesses the necessary qualifications or if external consultant expertise is needed Consultants, who may be engaged when investigators are not from the international site, can provide written protocol reviews or participate in IRB meetings to offer expert recommendations.

Federally funded research involving foreign institutions or sites can only proceed if the foreign entity has an Assurance with the Office for Human Research Protections (OHRP) and has obtained local Institutional Review Board (IRB) review and approval.

Approval of research for foreign institutions or sites “not engaged” in research is only permitted if one or more of the following circumstances exist:

When conducting research at a foreign institution with an established IRB/IEC, the Investigator must secure approval from the site's IRB/IEC or provide documentation confirming that such approval is unnecessary for the proposed research.

When a foreign institution lacks an established Institutional Review Board (IRB) or Independent Ethics Committee (IEC), it is essential to secure a letter of cooperation This letter must confirm that the relevant institutional or oversight officials authorize the research to be conducted at the designated performance site.

 IRB approval to conduct research at the foreign institution or site is contingent upon receiving documentation of the performance site’s IRB/IEC determination, or letter of cooperation, as applicable

1 It is the responsibility of the University investigator and the foreign institution or site to assure that the resources and facilities are appropriate for the nature of the research

The University investigator, along with the foreign institution or site, must ensure that the qualifications of the investigators and research staff are verified for conducting research in the respective country or countries.

The University investigator, along with the foreign institution or site, is responsible for ensuring essential activities are conducted, including the initial and ongoing review of research, monitoring post-approval, and addressing complaints, non-compliance, and unforeseen risks to participants or others involved.

4 The IRB will not rely on a local ethics committee that does not have policies and procedures for the activities listed above

University investigators and foreign institutions must promptly inform the IRB of any changes in research activities that affect the engagement of the performance site in the study, such as when a previously "not engaged" site begins to consent research subjects.

The informed consent documents must be in a language understandable to the proposed subjects, with the credentials of the translator detailed in the IRB application or amendment form

17.3.3 Monitoring of Approved International Research

The IRB is responsible for the ongoing review of international research conducted under its jurisdiction through the continuing review process in accordance with all applicable federal regulations

When the IRB and a local ethics committee will both be involved in the review of research, the

PI will be responsible for ensuring coordination and communication with the local IRB/IECs

The Principal Investigator (PI) must verify adherence to the provisions outlined in the International Compilation of Human Subject Research Protections, accessible via OHRP If the foreign institution lacks an Institutional Review Board (IRB), it is essential to secure a letter of cooperation from relevant institutional or oversight officials, authorizing the research to proceed at the designated site.

Registration of Clinical Trials

This institution requires PIs of certain investigator-initiated clinical trials to comply with federal requirements concerning registration of their studies on www.clinicaltrials.gov, no later than

21 days after enrollment of the first participant, if their study is described by any of the following:

To qualify as a clinical trial under NIH guidelines, a study must be funded wholly or partially by the NIH and affirmatively answer all four of the following questions.

1) Does the study involve human participants?

2) Are the participants prospectively assigned to an intervention?

3) Is the study designed to evaluate the effect of the intervention on the participants?

4) Is the effect that will be evaluated a health-related biomedical or behavioral outcome?

See https://grants.nih.gov/policy/clinical-trials/definition.htm for details

Not funded by the NIH, this clinical trial investigates drugs and/or biological products through a controlled clinical study, excluding Phase I investigations, and is subject to FDA regulations For more information, visit [ClinicalTrials.gov](https://clinicaltrials.gov/ct2/manage-recs/fdaaa).

The clinical study, which is not funded by the NIH, aims to evaluate health outcomes by comparing a device intervention with a control group in human subjects This study does not include any small feasibility studies or pediatric post-market surveillance, adhering to the regulations outlined in the Federal Food, Drug, and Cosmetic Act For more information, visit [clinicaltrials.gov](https://clinicaltrials.gov/ct2/manage-recs/fdaaa).

Many ICMJE journals require registration on clinicaltrials.gov for article publication The ICMJE defines a clinical trial as any research that assigns individuals to an intervention to examine the relationship between health-related interventions and outcomes Health-related interventions can include drugs, surgical procedures, devices, and behavioral treatments, while health outcomes encompass various biomedical measures, including pharmacokinetic data and adverse events.

Contact the Office of Research Compliance for first-time access to the clinicaltrials.gov site

17.5 Guidance on Research (only) Involving Coded Private Information or Biological Specimens

The Institutional Review Board (IRB) at Stony Brook University must carefully balance the protection of individual rights and welfare of biological specimen donors with the necessity of facilitating ongoing research activities.

The reader should also review Section 17.2, which addresses research involving tissue registries/tissue banks

According to 45 CFR 46.102(f), human subject research involves obtaining identifiable private information or specimens for research purposes This encompasses a range of activities that include collecting identifiable data and samples.

1 Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens that have been provided to investigators from any source; and

2 Using, studying, or analyzing for research purposes identifiable private information or identifiable specimens that were already in the possession of the investigator

OHRP defines private information or specimens as individually identifiable when they can be linked to specific individuals by investigators, either directly or indirectly through coding systems, as outlined in 45 CFR 46.102(f).

OHRP defines private information or specimens as not individually identifiable when investigators cannot link them to specific individuals, either directly or indirectly, using coding systems.

For example, OHRP does not consider research involving only coded private information or specimens to involve human subjects as defined under 45 CFR 46.102(f) if the following conditions are both met:

1 The private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; and

Investigators may be unable to identify individuals associated with coded private information or specimens due to several factors These include agreements between investigators and key holders that restrict access to the key until the individuals pass away, IRB-approved policies that enforce similar restrictions, or other legal requirements that prevent the release of the key until after the individuals are deceased.

The Institutional Review Board (IRB) mandates that investigators must obtain consent from prospective subjects whenever possible, especially in research involving the prospective collection of biological specimens Exceptions to this requirement, such as with future discarded surgical specimens, may be allowed only if a waiver of consent criteria is submitted and approved by the IRB.

When conducting research on biological specimens, it's essential to determine if the activity will yield clinically significant information that can aid in diagnosing or predicting disease states for both the subject and their family members.

If the answer is NO, the activity's non-physical risks are considered minimal, primarily theoretical, with potential clinical significance to be evaluated in the future The main concern then shifts to the risk of confidentiality breaches and the possibility that the subject remains unaware of the existence of this significant private information.

Where consent is required by the IRB, possible consent language in the procedures section (where consent is required) includes:

Test results from your tissue will only be meaningful when combined with data from other participants in the study As this is part of research, the clinical significance of your individual results may take years to determine Consequently, individual test results will not be provided to you or your doctor.

If the PI wishes to contact subjects if and when the clinical significance of the results becomes clear, possible consent language includes:

In the event that future research confirms the findings of this study with significant health implications for you or your descendants, we will strive to inform you through a letter detailing the results and available care or counseling options By initialing here , you indicate that you do not wish to be contacted regarding any future relevant findings.

If the answer is YES, the non-physical risks linked to the study are considered more than minimal, and these risks must be taken into account when preparing the foreseeable risks section of the consent document.

Policy on Payment of Research Related Injury Costs Due in Industry-funded and initiated

The Institutional Review Board (IRB) plays a vital role in supporting the University as a participant in industry-sponsored clinical trials, which include those initiated by pharmaceutical and device companies This involvement is essential for the effective evaluation and marketing of innovative investigational drugs, devices, and biologics, as well as new indications for already approved products.

Companies conducting industry-sponsored clinical trials are responsible for covering the costs of research-related injuries incurred by university subjects participating in these trials Volunteers will not be liable for these expenses, either directly or through their insurance Any exceptions to this policy will be evaluated individually, in consultation with the Institutional Official, the Office of Sponsored Programs (Clinical Trials Contracts division), and the Assistant Vice President for Research Compliance as necessary.

This policy codifies a longstanding procedural requirement of the Institutional Review Board (IRB) and does not intend to waive any legal rights of research subjects, nor does it absolve the investigator, sponsor, University, or its agents from liability due to negligence.

Research-related injuries refer to those that occur as a direct consequence of the test product or from properly executed study procedures These injuries do not encompass the natural progression of a participant's pre-existing condition or injuries arising from interventions that would have taken place regardless of the individual's involvement in the clinical trial.

Application of ICH-Good Clinical Practice (GCP)

The IRB evaluates research while investigators adhere to the “Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance” when required by the research sponsor, as specified in the study protocol In such instances, the investigator is responsible for ensuring compliance throughout the research process.

 Confirm compliance with these requirements, via review, completion, and uploading of the Supplemental Form D: ICH-GCP into the applicable electronic management system package

To ensure compliance with sections 3.1-3.4 of the referenced document, adhere to the following standard operating procedures for the study: all payments must be prorated, alternatives should be presented with a thorough risks and benefits assessment, costs and treatment related to injuries must be clearly outlined, subject responsibilities should be detailed in a distinct section, and subjects must receive a signed and dated copy of the Informed Consent Form (ICF).

Policy on Non-English Speakers as Research Subjects

17.8.1 Inclusion of Non-English Speakers

Non-English speakers should be included in research studies that offer potential therapeutic benefits, especially when there are no viable alternatives available in clinical care.

 Many of the cooperative oncology group protocols would qualify in this category, i.e testing experimental drugs that do not have a reasonable alternative in clinical care

 Certain studies involving potentially therapeutic benefit via non- or less- invasive procedures where the only clinical alternative would be invasive

For these types of studies, the special protections addressed in sections 17.8.2 and 17.8.3 below would need to be adequately addressed as a condition of IRB approval

Researchers must establish eligibility criteria for their studies that prioritize safety and the protection of vulnerable populations while aligning with the research's objectives Although not mandatory for IRB approval, it is essential to offer enrollment to all individuals who meet the study's eligibility criteria, regardless of their language proficiency.