Cardiac Safety Research Consortium: A Decade of CSRC. Mitchell W. Krucoff, MD, FACC

Transcription

1 Cardiac Safety Research Consortium: A Decade of CSRC Mitchell W. Krucoff, MD, FACC Professor, Medicine/Cardiology Duke University Medical Center Director, Cardiovascular Devices Unit Co-Director, CSRC Duke Clinical Research Institute [name of file], 1

2 Cardiac Safety Research Consoritum (CSRC) Origins [name of file], 2

3 Therapeutic Innovation in the USA 2004 R&D Spending & New Rx Applications 10 Year Trends

4 Cardiac Safety: Rare but catastrophic events 2006 FDA-Duke MOU Cardiac Safety Research Consortium

5 The Paradox Illusion 2006: Facilitating Innovation vs. Public Safety Faster The Spirit of the Slower Less Expense Critical Path: More Expense Less Safe Better safety Faster More Safe Cheaper

6 CSRC Mission To advance scientific knowledge on cardiac safety for new and existing medical products by building a collaborative environment based upon the principles of the FDA s Critical Path Initiative as well as other public health priorities.

7 The All Stakeholders Win-Win Perception The Pre- or Pro- competitive space Where raising the water level helps everybody s boat float a little better The Spirit of collaboration Would you be willing to share placebo data? Translating talking into doing Details and deliverables

8 Cardiac Safety Research Consoritum (CSRC) Who We Are & How It Works [name of file], 8

9 The CSRC Public-Private Partnership MODEL INDUSTRY ACADEMIA FDA Mortara Instrument CRADA PT. GROUPS PROFESSIONAL ORGANIZATIONS NON-PROFIT STATE, OTHER DCRI MOU NEUTRAL GROUND COMMITMENT ADM. INFRASTRUCTURE: HELP ESTABLISH WG/SC CONTRACTS MGNT COORDINATE MEETINGS FINANCIAL OVERSIGHT PUBLIC-PRIVATE CONSORTIUM PPP STEERING COMMITTEES WORKING GROUPS IDENTIFY MUTUAL PRORITIES POOL RESOURCES/EXPERTISE DEFINE ROLES/RESPONSIBILITIES GAP ANALYSES (WHAT S KNOWN?) CO-DEVELOP PROPOSALS BUDGETS TIMELINES RFPs IMPLEMENT PROJECTS

10 CSRC Executive Committee Chairs: Mitch Krucoff Duke John Finkle--GSK FDA: Norman Stockbridge David Strauss Health Canada: Colette Strnadova PMDA Japan: Kaori Shinegawa Operations: Valarie Morrow Duke Committee: Fabio Badilini--AMPS Mary Jane Geiger- Regeneron Gary Gintant AbbVie Cindy Green--Duke Peter Kowey- Lankenau Justin Mortara Mortara Inst. Ignacio Rodriguez Roche Philip Sager Consultant Tom Todaro- Medpace Rick Turner- Quintiles Theresa Wright Eli Lilly

11 CSRC Committee Structure Executive Member Opportunities Membership Theressa Wright Mitch Krucoff John Finkle Public Programs Thinktank Incubators Philip Sager Scientific Oversight Mary Jane Geiger Gary Gintant Research Projects ECG Warehouse Fabio Badilini Cindy Green External Partners Rick Turner White Papers Tom Todaro Signature Programs Peer Review Papers

12 Member Companies 2016 Abbott Dabi, Ltd Monebo AbbVie Daiichi Mortara Insrument AliveCor Duck Flats Pharma Merck Amgen Eli Lilly Nabios GmbH AMPS Epidemico OBS Medical Astra Zeneca Gilead Sciences Perspective Informatics AlCor G.E. Health Care Pfizer, Inc Bayer Global Instrumentation Portola Bioclinica GlaxoSmithKline Quintiles Biomedical Systems InVivo Sciences Roche Boehringer Ingelheim Johnson & Johnson Salix Cardiocore Medifacts Sanofi Aventis CardioNet Medpace Takeda Celerion Medtronic Taylor Microtech Chiesi Pharma Merck Vince & Associates CytoVas

13 Partnering Organizations DIA HESI ACC-NCDR ICOS NIH AHA FDA Health Canada PMDA Japan

14 DIA-CSRC Preferred Partnership Cardiac Safety & Education Consortium (CSEC) Themes: Drug-Device Safety Pediatric safety Social listening Phases: Didactic conference Consensus paper Thinktank/Incubator White paper SOC Project

15 Cardiac Safety Research Consoritum (CSRC) Accomplishments & Memorable Moments [name of file], 15

16 CSRC

17 The Pre-CSRC Thinktank: October 11, 2005 Would you be willing to share placeboexposure ECGs? Absolutely NOT! CSRC: FREE THE WAVEFORMS

18 QT Warehouse Training Set/Test Set Public Access Rules of Engagement

19 QT-Algorithm Analysis Comparisons Sample automated reanalysis (in red) compared with sponsor submission (in blue) of Dataset 4: Moxifloxacin vs Placebo double delta (Learning set #1, released)

20 Advancing Technology Platforms: First Final Exam Report: Qtino Green CT et al, Am Heart J 2012

21 ECG Warehouse SubCommittee: Genetic Long QT Warehouse New CSRC repository ECGs from genetic LQTS mutations & families French registry c/o Dr. Pierre Maison-Blanch 537 ECGs from 312 subjects Uploaded October 25, 2012 Digital upload c/o Fabio Badilini (AMPS)

22 DES Stent Thrombosis: 2006

23 Obligatory Drug-Device Safety Interactions DES & Extended Dual Antiplatelet Therapy: February 2007, April 2007, September 2007 Regulatory FDA: E.U. CDER CDRH Off Comm Austria U.K. Sweden Japan: MHLW PMDA Academia Duke Harvard Cleveland Clinic Columbia U of NM Wash Hrt Ctr London School of Hyg & Trop Med CVPath Societies ACC SCAI ESC Federal NIH AHRQ Industry Abbott Medtronic BSCI Cordis/J&J Biosensors OrbusNeich Eli Lilly (Daichi) Sanofi BMS

24 Dual Antiplatelet Therapy (DAPT) RCT Initial Procedure Enrollment Randomization (All Eligible Subjects) End of Treatment End of Follow Up 0 12 m 30 m 33 m 30 m DAPT arm Obs DES n = 15,245 BMS n = 5,400 Open label DAPT R DES n = 12,196 BMS n = 4,320 Double Blind Placebo Controlled RCT 12 vs 30m randomization in subjects clear and on treatment at 12m Stratified by lesion and clinical complexity Co primary endpoints: ST and MACCE, Safety endpoint: Major bleed 33 months follow up, to include 3 month rebound period Simultaneous RCT of 12 vs 30m DAPT in BMS Both clopidogrel and prasugrel 12 m DAPT arm Obs

25 The DAPT Study 2014 DES: 9,961 pts SES, PES, ZES, EES BMS: 2,816 pts Inclusion: 1 year clear RCT: >1 yr placebo vs. thienopyridine Clopidogrel, Prasugrel Co-1 O Endpoint: mos: ARC Def/Prob ST MACE (Death, MI, Stroke) 1 O Safety: mos GUSTO bleeding Mauri L et al, NEJM 2014

26 The TREAT Initiative Cardiac Safety & Bleeding Risk in Women 2010

27 September 2013 Lauer M et al, NEJM 2013 Hess C et al, Am Heart J 2013 Rao S et al JACC Cardiovascular Int 7(8)2014

28 CSRC Consensus White Papers

29 A Decade of Topical Areas Novel QTc Pro-arrhythmia drug-device safety interactions Women s CV safety Randomized RCT Pediatric sudden death Biomarker monitoring Blood pressure monitoring Imaging Cardio-oncology Registry-based RCTs CV event reporting (CRFs) CV event adjudication (CEC) Social listening Oncology agents Diabetes agents NOAC antitdotes Pediatric devices Biologics

30 Fiscal Instability

31 Cardiac Safety Research Consoritum (CSRC) Our Most Memorable Accomplishment: Moving Into A Second Decade [name of file], 31

32 CSRC 5- & 10-year Conclusion: Taking Cardiac Safety Into the 21 st Century The fabric of the CSRC and the key to past and future success is our membership engaged, creative individuals with diverse professional backgrounds a brain-trust of unique breadth and depth.our members have developed trust in each other and in the CSRC s pre-competitive PPP processes trust that we come together to listen to each other to exchange and discuss ideas.trust that our pragmatic emphasis is productive, with deliverables that have impact on the landscape of cardiac safety. If you want to go fast Go alone If you want to go far Go together African Proverb

33 Cardiac Safety Research Consortium: A Decade of CSRC Mitchell W. Krucoff, MD, FACC Professor, Medicine/Cardiology Duke University Medical Center Director, Cardiovascular Devices Unit Co-Director, CSRC Duke Clinical Research Institute [name of file], 33

34 CSRC