VHA Meeting Pham How To Do Research

What They Have in Common? “Vision: Build & They Will Come” How to Conduct A Successful Clinical Research? Dr Phạm Thành An Why Clinical Research in Viet Nam?        Nearly 3.7 billion people are living in Asia or 56.3% of worldwide population ~88 million in Viet Nam JUPITER trial, 2008: N=17,802 patients; 71.4% White; 12.4% Black; 12.6% Hispanic; 3.6% Other/Unknown ethic group ALLHAT trial, 2002: N=42,418; 47.2% White; 31.9% Black; 15.8% Hispanic; 5.1% Other More participation to balance study subjects and principal investigators is needed Rosuvastatin, 2004 - FDA approved starting dose is 5mg for Asians & 10mg for Caucasians based on kinetic data in Asia Isoniazid (INH), 1976 - majority of Asians were discovered to be fast acetylators (1) Crestor, Prescribing Information, 2009; (2) Myers FH, Rev of Med Pharm, th Ed, Lange Med Publications; (3) Ridker PM, JUPITER Study, NEJM, 2008, 359:2195-207; (4) ALLHAT Study Group, JAMA, 2002: 288:2981-97; (5) US Census Bureau, World Population Estimates SHARP Trial Article-in-Press Work-in-Progress - 2010 LANCELOT-ACS Trial 2010 TCT, Washington, DC Top Enrolling Countries (184 sites, 22 countries) Poland 22.7% Bulgaria 4.1% India 15.6% Italy 1.8% Russia 13.3% UK 1.8% Israel 9.3% France 1.7% Germany 7.1% Argentina 1.5% Belgium 6.6% USA 1.5% South Africa 4.8% Australia 1.3% Role & Responsibility of Researcher Types of Research  Epidemiological  Observational  Retrospective/Meta-analysis  Prospective Responsibilities   Complete “Form FDA 1572” (Statement of Investigator) for drug developments or Investigator Agreement for medical devices Ensure that a study is personally conducted and supervised according to      Signed investigator statement, Investigational plan, Applicable regulations IRB and informed consent Record retention for years after study discontinuation What Are the Basic Elements for Successful Clinical Research? R’s  Right Passion    Right Infrastructure/System    Robust Registry Database Comprehensive/Accurate Reporting System Right Patients    New Knowledge/Discovery Evidence-Based Question Large Pool of Eligible Patients Good Follow Up Mechanism Right People   Research Staff Large Network/Consortium Successful Data Registry Requirement Accomplish the R’s To Have the:    Right Data Collected at the Right Time by the Right Person Know Your Patient & Capability  Patient Characteristics  Disease Prevalence  Generate research hypothesis United States Experiences in Data Registries: The Acute Coronary Syndrome Patients Acute Coronary Syndrome (ACS), UA/NSTEMI (Unstable Angina/Non ST-Segment Elevation Myocardial Infarction) & STEMI (ST-Segment Elevation Myocardial Infarction): Why Targeted ACS? 1.72 Million Hospital Discharges for ACS STEMI 0.42 Million Discharges per Year UA/NSTEMI 1.3 Million Discharges per Year ACS is an umbrella term covering any group of clinical symptoms compatible with acute restriction of blood flow to the heart muscle Baseline Lipids and Lipoproteins Fasting Serum Lipid and Lipoprotein Levels at Baseline (n=1,873) Concentration (mmol/L) Concentration (mg/dl) Total Cholesterol 5.74 222 LDL Cholesterol 3.60 139 HDL Cholesterol 1.49 58 Triglycerides 1.42 126 Apolipoprotein B - Values given as mean 1.31 (g/L) SD; LDL = low-density lipoprotein; HDL = high-density lipoprotein Baseline Echocardiography Mean Values Placebo Simva + Ezetimibe n= 929 n= 944 Peak velocity (m/sec) 3.10 3.09 Peak gradient (mmHg) 39.6 39.3 Mean gradient (mmHg) 23.0 22.7 Aortic valve area (cm2) 1.27 1.29 Bicuspid valve (%) 6.3 5.0 Transaortic Results: LDL-Cholesterol Intention to Treat Population 150 Placebo Mean (mg/dL) SE 125 100 75 50 EZ/Simva 10/40 mg 25 0 0.5 1.5 2.5 Year 3.5 4.5 5.5 Primary Endpoint MACE Percentage of Patients With First Event 50 Intention to Treat Population Placebo 40 Hazard ratio: 0.96, p=0.591 30 EZ/Simva 10/40 mg 20 10 0 No at Risk Years in Study EZ/Simva 10/40 mg 906 817 713 618 53 Placebo 884 791 696 586 56 2nd EP: Percentage of Patients With First Event 50 Aortic Valve Events Intention to Treat Population 40 Placebo 30 Hazard ratio: 0.97, p=0.732 EZ/Simva 10/40 mg 20 10 0 No at Risk EZ/Simva 10/40 mg Placebo 914 895 Years in Study 836 814 732 725 635 611 55 58 Aortic Valve Replacement 50 Percentage of Patients With First Event Intention to Treat Population 40 Placebo Hazard ratio: 1.00, p=0.968 30 20 EZ/Simva 10/40 mg 10 0 No at risk Placebo EZ/Simva 10/40 mg 896 915 Years in Study 816 837 728 734 618 61 640 55 Peak Aortic - Jet Velocity 0.75 Intention to Treat Population Change from Baseline (m/sec) Mean ( SE) 0.60 0.45 0.30 EZ/Simva 10/40 mg 0.15 Placebo 0.00 Year Year Time Last Follow-up 2nd EP: Percentage of Patients With First Event 30 20 Ischemic CV Events Intention to Treat Population Hazard ratio: 0.78, p=0.024 Placebo EZ/Simva 10/40 mg 10 0 No at risk EZ/Simva 10/40 mg Placebo Years in Study 917 898 867 838 823 788 769 729 76 76 Coronary Artery Bypass Grafting (CABG) 30 Percentage of Patients With First Event Intention to Treat Population 20 Hazard ratio: 0.68, p=0.015 Placebo 10 EZ/Simva 10/40 mg 0 EZ/Simva 10/40 mg 925 887 848 797 80 Placebo 909 862 819 761 80 No at risk Years in Study All Cause Mortality Cumulative Percentage 30 Intention to Treat Population Hazard ratio: 1.04, p=0.799 20 EZ/Simva 10/40 mg 10 Placebo 0 No risk EZ/Simva 10/40 mg Placebo 930 916 Years in Study 912 890 884 865 855 835 89 94 Clinical Adverse Events (AE)- Safety All Patients as Treated Population Placebo N=929 n EZ/ Simva N=943* n Any serious AE (SAE) 463 468 Drug d/c due to SAE 79 77 Musculoskeletal AE 181 165 Myopathy / Rhabdo 0 p= 0.28 Marketing Your Study Site Network   Colleagues (sub-investigator or co-investigator) List your site on internet services     www.clinicalinvestigators.com; www.acurian.com Community health fairs screening eligible subjects Scientific conferences & exhibit booths Direct contact with trial sponsors or Contract Research Organization (CROs) Site Profile for Marketing Distribution   Highlight your unique strengths and subject population Emphasize past trial experiences & enrollment goal performance Resources & Networking  Clinical Trial Networks Best Practices   International/Academic Collaboration    Duke Clinical Research Institute (DCRI)  www.dcri.duke.edu TIMI Study Group – www.TIMI.org Oxford University – www.ctsu.ox.ac.uk/projects Clinical Trial Registries – www.clinicaltrials.gov Clinical Trial Results – www.clinicaltrialresults.org   www.ctnbestpractices.org Conclusions     Data registries excellent tools for clinical research Clinical researches address unanswered questions Asian patients & investigators needed worldwide Participation in finding solutions:    Better treatment strategies New/better treatment options Reduce morbidity/mortality Questions & Comments Thank You! Contact Information: An Pham 1909 SW Cove Point Rd Seattle, WA 98146 - USA Email: apham98146@gmail.com Phone: 1-(206) 459-6290 ...“Vision: Build & They Will Come” How to Conduct A Successful Clinical Research? Dr Phạm Thành An Why Clinical Research in Viet Nam?        Nearly 3.7 billion people... 15.8% Hispanic; 5.1% Other More participation to balance study subjects and principal investigators is needed Rosuvastatin, 2004 - FDA approved starting dose is 5mg for Asians & 10mg for Caucasians... kinetic data in Asia Isoniazid (INH), 1976 - majority of Asians were discovered to be fast acetylators (1) Crestor, Prescribing Information, 2009; (2) Myers FH, Rev of Med Pharm, th Ed, Lange