Neuro-Ophthalmology Research Disease Investigator Consortium www.NORDICclinicaltrials.com _ SPECIALIZED PROJECTS and CLINICAL TRIALS in NEURO-OPHTHALMOLOGY and VISUAL NEUROSCIENCE _ NORDIC Headquarters 1000 10th Ave 10th Floor – INN 11th Floor – NORDIC Offices New York, NY 10019 July 2010 212-636-3516 July 2010 Introduction Neuro-ophthalmology is a subspecialty of Neurology and Ophthalmology that is focused on the scientific and medical issues of both specialties Almost no prospective information exists on many Neuro-ophthalmologic disorders; and with the lack of precise historical data on the visual and systemic health, ophthalmologists, neurologists, internists and family practitioners continue to perform many unnecessary, expensive, and potentially invasive tests and to treat patients without evidence-based medical guidance This can result in initiating therapies that can be hazardous without a clear rationale Many neurological and systemic disorders affect the vision system, from the retina to the occipital lobe and/or disrupt ocular motility causing many types of visual loss and distortion, interfering with every aspect of daily living activities Precise, reproducible, standardized and accurate functional, structural and electrophysiological assessments mean that these diseases and new therapies can be investigated in prospective studies and clinical trials NORDIC designs and manages these studies, providing agencies and sponsors a network with the data needed to advance therapeutic interventions NORDIC was first conceived to address the many Neuroophthalmologic illnesses, although uncommon, which have devastating effects on affected individuals Individual or small groups of Neuroophthalmologic investigators typically not evaluate enough subjects with most of these disorders to recruit an adequate number of subjects; to answer the many unanswered questions about visual outcome, relation to systemic illness, and effectiveness of current and future therapeutic interventions that require multi-site observational and treatment trials Establishing a consortium with a formal organization, single data coordination and biostatistics center and a July 2010 network of investigators will permit the majority of Neuroophthalmologists to participate in multi-site observational and treatment trials, facilitate the integration of new medical/scientific concepts, and ensure recruitment of the necessary number of subjects for each study Additionally, this consortium and network will allow long range observational studies to be included (in order to collect prospective data so that the more expensive and focused treatment trials will be designed) or provide answers without a more expensive single purpose clinical trial “NORDIC is about conducting research to solve the major issues that affect treatment of the eye and neurological disturbances that disrupt vision.” … M Kupersmith, MD, NORDIC Chair About NORDIC The Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) is a specialized scientific research organization, created to facilitate the performance of multi-site observational and treatment trials The first aim of the consortium was and remains to answer many important unanswered questions concerning risk, diagnosis, treatment and management of Neuro-Ophthalmological conditions with focus on the research of scientific and medical issues affecting vision, eye movements, pupil function, and visual quality of life NORDIC has expanded to perform planning, designing and conducting of clinical trials to evaluate new therapies and vision system toxicity of agents, using precise functional and structural assessment of the vision system NORDIC has developed clinical sites and committees essential for the start-up, conduct and close-out of a clinical trial as well as to oversee the organizational component of the consortium The Executive Committee (EC) coordinates all NORDIC activities with the Data and Safety Monitoring Board (DSMB) and manages organizational structure, including the network sites, the Data Coordination and Biostatistics Center (DCBC), all committees, and reading centers The Scientific Review Committee (SRC) provides input on the feasibility and science of a proposed clinical trial The Planning Steering Committee (PSC) and Study Steering Committee (SSC) provide continued oversight of the study including experimental design, the review process, enrollment, quality control, and statistical analyses July 2010 Data and Safety Monitoring Board (DSMB)* is composed of a group of individuals not directly involved in subject care or data collection in the trial The Quality Assurance Committee provides oversight to ensure quality control throughout the lifecycle of a clinical trial and to ensure that every clinical trial is conducted with the highest level of regulatory standards *The DSMB provides periodic review of accumulated data for evidence of adverse or beneficial treatment effects, review the ethical conduct of a study, initiate recommendations for modification of the study protocol, including termination of the treatment when appropriate and assessing data quality and site performance “The NORDIC approach is a joint development leadership structure that spans POC/pilot studies, translational, clinical and academic research.” … Regional Project Coordintor NORDIC has initiated a network of clinical trial sites throughout the US and Canada (with planned expansion to Europe, Israel and Australia) A recent launch of 42 certified sites within the network will increase the productivity and effectiveness of neuro-ophthmological clinical research NORDIC will continue to build a network of experienced Neuro-ophthamologists to conduct research and the investigators will be able to recruit within their own patient population Rather than select new sites and new investigators for every clinical trial, the network of sites will be available for all NORDIC clinical trials NORDIC Expertise NORDIC understands how vital specialized therapeutic knowledge and experience are to delivering success in trials involving neurology and ophthalmology All of NORDIC’s certified Principal Investigators have demonstrated extensive experience, both in the clinic, and in the practices of performing the highest level of trial research Each member of our team is capable of providing service to differing trial types, i.e long-range observational, biologic, pharmaceutical, diagnostic, and government-sponsored Regardless of the design, NORDIC’s highly-experienced team has a full understanding of their trials With specific expertise in vision system basic to clinical research, NORDIC has developed, validated, and standardized outcome measures that can be used in clinical trials Standardized high contrast July 2010 and low contrast acuity are tested using the same display apparatus that is internally monitored All sites have the same threshold perimeter and softwared Most sites have the same spectral high definition optic coherence tomography and latest software Fundus photography is standardized across all sites NORDIC has the only OCT Reading Center for spectral OCT studies The Neuro-Ophthalmology Visual Quality of Life Assessment tool is one measure NORDIC uses to correlate the subject/patient perception with these measures The Certified Clinical Trial Site Advantage The network of certified sites was created by NORDIC to provide organizational and operational assistance to researchers in academia, industry, government and non-profit institutions NORDIC promotes the pursuit of innovative clinical research through the connection of resources that historically stood as a barrier to the performance of such trials Investigators will be trained and certified for participation in treatment trials and observational studies, and will be updated on procedures at least once a year Before a clinical trial site within the network can actively begin a clinical trial for NORDIC, the site personnel must complete certification in visual acuity and refraction, visual fields, fundus photography, optical coherence tomography, and lumbar puncture The purpose of the certification requirement is to assure that, to the extent possible in a multi-center clinical trial, procedures are being performed in the same way and in accordance with the study protocol in all network sites The certification program is supervised by the NORDIC Quality Assurance Committee and conducted by the NORDIC Reading Centers July 2010 NORDIC Reading Centers Visual Acuity/Refraction – University of Iowa Visual Field – University of California, Davis Fundus Photography – University of Rochester Optical Coherence Tomography - University of California, Davis The NORDIC Approach NORDIC is an open investigator group, organized to provide a structured environment for clinicians interested in studying NeuroOphthalmological disorders through participation in clinical research studies The consortium approach also provides the ability to incorporate managed care settings as well as traditional private practice and medical center locales into clinical trials This provides researchers the ability to reach out to the maximum number of potential participants, despite the challenges posed by the continuous change in the delivery of health care Developed to provide strong central coordination of all participating sites, NORDIC’s operational strategy has been designed to ensure that approved protocols can be easily incorporated into standard clinical practice All Network sites adhere to the guidance of NORDIC management, headed by a governing Chair and Executive Committee (EC) NORDIC’s operational functions are managed by leaders in the neuro-ophthalmic therapeutic area and in the clinical research sector With the added appointment of each clinical study, a customized Study Steering Committee (SSC) is recruited, and data collection/ management requirements are assessed by a Data Coordination and Biostatistics Center (DCBC), staffed by persons qualified in managing data generated by national and multi-site studies Additionally, a Photographic Reading Centers (PRC) and Visual Field Reading Center July 2010 (VFRC) have been appointed to provide significant neuro-ophthalmic assessments when specified by the protocol “NORDIC addresses common as well as rare problems that affect the eye movements, optic nerve and brain We apply methodology to evaluate the latest translational research as well as established therapies, for efficacy and toxicity” … M Kupersmith, MD, NORDIC Chair The Challenge of Quality Data An ongoing challenge in managing the quality of clinical data is to continually monitor data collection procedures at every level of the clinical trial The efficiencies and cost-savings of using one data coordination and biostatistics center (DCBC) and having one organizational framework to foster, develop, and administer multiple studies are obvious Conducting clinical trials of such scientific significance using a dedicated organization will ensure that standards of quality are being met “The NORDIC team provides a mutual exchange of time, resources and research expertise.”… NORDIC Headquarters Clinical Trialist For each NORDIC clinical trial, the DCBC staff, in conjunction with the Study Steering Committee (SSC), has the responsibility for overseeing the development of the protocol, development of operational and analytical methodology, the conduct of each study according to the protocol, and analysis of all data The DCBC serves as an administrative resource for study investigators The center is actively involved in facilitating initial IRB approvals, yearly renewals, amendment approvals and centrally tracking all of the final approved documents Each site is trained to collect and enter quality data to the DCBC secure electronic capture Specific FTP sites are used to upload visual field, OCT, and fundus photography This allows immediate feedback and exceptional quality control from the NORDIC Reading Centers Organizational and Operational Support NORDIC offers services from comprehensive feasibility and project management to clinical monitoring and patient recruitment services Through efficient utilization of the resources joined in networking an July 2010 extensive group of Neuro-Ophthalmologists, NORDIC is leading the way to conduct statistically-valid, cost-effective clinical trials in Neuroophthalmology The NORDIC Team includes experts in pilot study creation, clinical trial design, outcome measures, biostatistics, quality of life determinations, vision and nervous system toxicity Available services include: • • • • • • Project Development and Planning Protocol Development Consulting Services Case Report Form Design (EDC) Administrative Services Reporting Services • Site Monitoring • • • Safety Monitoring Clinical Materials Services Central Laboratory Services • • Meeting Coordination Biostatistics Network of Clinical Trial Sites The following US-based and Canadian-based centers are the current NORDIC network of clinical trial sites: Canada Hotel Dieu Hospital, Kingston, Ontario, Canada The Montréal General Hospital, Montreal, Quebec, Canada United States Bascom Palmer Eye Institute, Miami, Fl Bethesda Neurology, LLC, Bethesda, MD Beaumont Eye Institute, Royal Oak, MI Casey Eye Institute, Portland, OR Dean A McGee Eye Institute, Oklahoma City, OK Department of Ophthalmology at UAB, Birmingham, AL Department of Ophthalmology and Visual Sciences, Iowa City, IA Doheny Eye Institute, Los Angeles, CA Duke Eye Center, Durham, NC Greater Baltimore Medical Center, Baltimore, MD Jules Stein Eye Institute, Los Angeles, CA LSU Surgical Facility, Baton Rouge, LA Medical University of South Carolina, Charleston, SC Massachusetts Eye and Ear Infirmary, Boston, MA Michigan State University, East Lansing, MI Mount Sinai Medical Center, New York, NY, NY Neuro-ophthalmic Consultants Northwest, Seattle, WA Neuro-Ophthalmology & Balance Disorders Clinic, Tallahassee, FL Neuro-ophthalmology Department of Neurology, Peoria, IL New Jersey Medical School, Newark, NJ New York Eye and Ear Infirmary, NY, NY July 2010 OSU Eye Physicians and Surgeons, LCC, Columbus, OH Raleigh Neurology Associates, Raleigh, NC Saint Louis University Eye Institute, Saint Louis, MO Stony Brook Ophthalmology, Stony Brook, NY SUNY Upstate Medical University, Syracuse, NY The Emory Clinic – Emory University, Atlanta, GA The Eye Care Group, New Haven, CT University Eye Institute, Houston, TX University of Colorado, Aurora, CO University of Michigan, W.K Kellogg Eye Center, Ann Arbor, MI University of Minnesota, Minneapolis, MN University of Pennsylvania, Dept of Ophthalmology, Philadelphia, PA University of Rochester Eye Institute, Rochester, NY University of St Louis, St Louis, MO University of Texas Science Center, San Antonio, TX University of Utah, John A Moran Eye Center, Salt Lake City, UT University of Virginia, Charlottesville, VA Wake Forest University Eye Center, Winston-Salem, NC Wilmer Ophthamological Institute, Baltimore, MD For More Information NORDIC has developed a web-site to ensure access to NORDIC resources, enhance communication, and encourage information sharing For a full description of NORDIC as a scientific research organization, the web-site addresses NORDIC Policies, Mission Statement and Current Research RFI can be obtained at info@NORDICclinicaltrials.com New study ideas or a RFP can be submitted at NORDIC@NORDICclinicaltrials.com 10 ... affecting vision, eye movements, pupil function, and visual quality of life NORDIC has expanded to perform planning, designing and conducting of clinical trials to evaluate new therapies and vision... ongoing challenge in managing the quality of clinical data is to continually monitor data collection procedures at every level of the clinical trial The efficiencies and cost-savings of using... knowledge and experience are to delivering success in trials involving neurology and ophthalmology All of NORDIC’s certified Principal Investigators have demonstrated extensive experience, both in the