Professional Society Roles in Drug-Device Cardiac Safety

Transcription

1 Professional Society Roles in Drug-Device Cardiac Safety TREATT II Thinktank Silver Spring, MD March 7, 2011 Ralph Brindis, MD MPH FACC President, American College of Cardiology Senior Advisor for CV Disease N. Cal Kaiser Permanente Clinical Professor of Medicine, U.C.S.F.

2 Disclosures I am a Recovering Interventional Cardiologist ACC has a business relationship with Prism/Health Outcomes Sciences

3 The Triumvirate in Cardiac Safety Industry Sponsors Regulators FDA- Payers Academia- Professional Societies

4 Health Care Reform CER & Cardiac Safety True Tipping Points for huge leaps in Cardiac Safety ARRA Grants for CER Builds infrastructure also valuable for cardiac safety Funding for longitudinal databases Improvement in patient matching The holy grail of UPI vs Probabilistic Matching Increased alignment of payers (CMS), FDA, Industry, Professional Societies and Academics

5 HealthCare Information Technology More Tipping Points for Cardiac Safety Paper based records being replaced with: Electronic Health Records Device Telephonic Assessments Computerized Databases Standardized Data Definitions Robust Professional Society National Registries although siloed and episodic/procedure based Development of Linked Databases for true longitudinal assessment

6 Professional Society Roles Academia/Professional Societies Provide focused expert input (with transparency regarding conflicts of interest) Serve on DSMB / DMC / Adjudication committees Contribute to guideline development, competency and accreditation standards, AUC, whitepapers, policy documents, writing groups and ACE Act as a trusted third party for data NCDR, post-market Represent the patient - express opinions as to what might be acceptable safety risks.

7 National Cardiovascular Data Registry Imaging Registry Timeline and growth ICD Long IMPACT Registry AF Abl Registry PINNACLE PAD Registry CathPCI Registry ICD Registry CARE Registry ACTION Registry Valve Registry beyond

8 CathPCI Age Distribution 36% over 70 years of age 14%

9 National Data Repository for Comparative Effectiveness Research Pharm STS Registry UPI NDI NCDR CATHPCI CLAIMS

10 ACC/Duke Partnership: Develop a National Cardiovascular Research Infrastructure (NCRI)

11 In-Hospital Outcomes - STEMI vs. NSTEMI Variable STEMI (n=28,614) NSTEMI (n=44,528) Death* 5.7% 4.0% Re-infarction 1.0% 0.9% CHF 6.1% 6.7% Cardiogenic Shock 6.4% 2.9% Stroke 0.9% 0.8% RBC Transfusion** 5.7% 7.6% Major Bleeding** 11.4% 9.2% ACTION Registry-GWTG DATA: July 1, 2009 June 30, 2010 *Unadjusted mortality ** Among non-cabg pts

12 % Excessive Dose Excessive Dosing of Anticoagulants by Age LMW Heparin UF Heparin GP IIb/IIIa yrs 65 < yrs yrs 75> Alexander KP, et. al. JAMA 2005

13 Excess dosing of Gp IIb/IIIa and bleeding in women N=32,601 patients from CRUSADE Overall 1.46 (1.22, 1.73) Women 1.72 (1.30, 2.28) Men 1.27 (0.97, 1.66) Excess Dosing More Likely to Bleed Alexander KP, et. al. Circulation 2006

14 NSTEMI Acute Medication Overdosing Trends 25% 20% 15% 10% UFH* LMWH# GP IIb-IIIa 5% 0% * Infusion (> 15 units/kg/hr) or bolus (> 70 units/kg) # Initial dose (> 1.05 mg/kg) or total 24 hr dose (> 10 mg over recommended) Q Q Q Q ACTION Registry-GWTG DATA: July 1, 2009 June 30, 2010

15 PRISM Models Bleeding Peri-Procedural Bleeding Complications Model Based upon NCDR Cath/PCI Registry» Uses pre-procedural data» Built upon 302,152 procedures from 440 sites» C-statistic = 0.73 Stratifies patients into 3 risk groups» Low risk: <1%» Moderate: 1-3%» High risk: >3% Mehta SK et al. Circ Cardiovasc Intervent 2009;2:

16 Potential Interventions for High Bleeding Risk Interventions to Consider: Use of Bivalirudin Use of Closure Device Radial Approach Admission as an Inpatient for Observation Recommendations: Low Risk No Recommendation Moderate Risk At least 1 Intervention High Risk 2 or More Interventions

17 Bleeding (%) Use of bleeding avoidance strategies among patients undergoing PCI The Risk-Treatment Paradox M = Manual comp. C = Closure only B = Bival only BC = Bival+closure M C B BC M C B BC M C B BC Low Risk Intermediate Risk High Risk Marso et al. JAMA 2010;303(21): Amin et al. Circ Cardiovasc Qual Outcomes 2010;3:

18 Physician Individual Reports Dr. Cardiologist

19 Risk of Local Adverse Effects Following Cardiac Catheterization by Hemostasis Device and Gender A Report from the NCDR in Partnership with the FDA Dale Tavris, Syamal Dey, Albrecht Gallauresi, Richard Shaw, William Weintraub, Kristi Mitchell, Ralph Brindis Grant from Office of Women s Health, Food and Drug Administration

20 Risk of adverse events following cardiac catheterization by hemostasis device use Only one device, VasoSeal, demonstrated a high risk of any vascular complication compared to manual compression controls (OR = 2.38 [ ; p = ]) This resulted in VasoSeal being taken off the market Tavris et al. J Invasive Cardiol Dec;17(12):644-50

21 Outcomes Following Coronary Stenting: A National Study of Long Term, Real-World Outcomes of Bare-Metal and Drug-Eluting Stents Pamela S. Douglas, J. Matthew Brennan, Kevin J. Anstrom, Eric L. Eisenstein, David Dai, Ghazala Haque, David F. Kong, Ralph Brindis, Art Sedrakyan, David Matchar, Eric D. Peterson Duke Clinical Research Institute Duke University Medical Center

22 Goal and Population Goal To examine comparative effectiveness and safety of DES vs BMS in a national PCI cohort Study population All PCI pts > 65 yo in NCDR CathPCI 1/04-12/06 Follow up obtained through linkage to CMS inpatient claims data using indirect identifiers; 76% matched Final cohort 262,700 pts 83% DES; 46% Cypher, 55% Taxus

23 Analysis 30 month outcomes Death, MI, Stroke, Revascularization, Major bleeding Overall and in important subgroups

24 Rate / 100 patients Outcomes Following Coronary Stenting A National Study of Long Term, Real-World Outcomes of Bare-Metal and Drug-Eluting Stents DES & BMS Event Rates:30-month Adjusted

25 Landmark Display: Mortality

26 DES v BMS Population Sub-study To create a data set in which the national, real world outcomes following PCI can be assessed To examine the comparative effectiveness and safety of DES vs BMS To examine the comparative effectiveness in understudied and special populations Sex, age, race Chronic kidney disease Off label lesions

27 Off- Label Lesions 186,111 patients; Off label lesions in 128,507 (69%) 109,734 (85%) received DES 46% received SES and 54% received PES Specific lesions considered 50% High risk, Type C 12% bifurcation lesions 6% in-stent restenosis 6% chronic total occlusion 4% left main lesions 9% saphenous vein grafts AHA % arterial grafts

28 HRS and ACC ICD Registry Post Market Surv. NQF Perf. Measure- Risk adjusted/icd Registry- Medicare Claims Data for 30 and 90 day complications: Death, pneumo/hemothorax, transfusion or surgical evacuation, tamponade or pericardiocentesis, system/lead revision, infection 90 days, ICD replacement 90 days. ICD Registry leads data to assess lead performance as part of the FDA sentinel network.

29 TReatment with ADP receptor inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome

30 Study Organization Academic Research Organization Duke Clinical Research Institute PI Eric Peterson, MD, MPH Co-PI Tracy Wang, MD, MHS, MSc Steering Committee Kevin Anstrom, PhD David Cohen, MD Mark Effron, MD Gregg Fonarow, MD Tim Henry, MD Dan Mark, MD John Messenger, MD Mandeep Singh, MD Gregg Stone, MD Collaborating Partners American College of Cardiology Food and Drug Administration Sponsor Eli Lilly and Company/Daiichi Sankyo, Inc

31 Prospective, observational study of antiplatelet treatment among AMI patients treated with PCI Clopidogrel or Prasugrel or (Ticagrelor) Objectives: to evaluate long-term effectiveness and safety adoption of novel antiplatelet meds short- and long-term treatment patterns antiplatelet medication switching patient adherence economic cost implications FOLLOW-UP Validated events, medications, costs Index AMI Hospitalization 1 Discharge Months

32 DELTA Project Resnic JAMA. 2010;304(18): Automated Safety, Effectiveness & Quality Monitoring FDA sponsored project of automated active medical device safety surveillance with national clinical registries Safety alert triggered if cumulative observed risk for device >95% confidence interval of comparator control device. CV Device Safety Steering Committee ACC-NCDR, FDA-CDRH, DELTA/BWH

33 Clinical Registries & Automated Surveillance: Postprocedure Safety Signals of CV Devices Prospective propensity matched cohort analysis of 7 CV Devices via NCDR/MA data Safety alert if device > 95% CI of comparator device control Found sustained alerts in 2 devices in 75,000 patients Stent with increased MI rate/major adverse cardiac events and a Closure device with increased vascular complications Resnic, et al JAMA 2010;304:

34 DELTA Auto-Surveillance Angio-Seal STS Resnic JAMA. 2010;304(18): Major Vascular Complications Longitudinal propensity-matched analysis of cumulative incidence. Dark blue circles, > expected rates (safety alerts)

35 Perfect Surveillance World Safety monitoring for drugs and devices hardwired into distribution system at point of care Drugs and devices with real risk need real time data gathered into existing databases managed at point of care and capable of tracking pts longitudinally Device identifiers and UPIs!! Post approval safety monitoring should be a public trust shared: Sponsors, regulators, and trusted third parties (academics, ACC/HRS, patient advocates) Real time data feedback to prescribers at point of care! (Hertz Car analogy)

36 Diffusion of Innovation - Safety Intra Professional Society Collaboration STS, ACC, AATS, SCAI, HRS Percutaneous Aortic Valves Mitral Repair Atrial Fibrillation Ablation Operator and Institutional Requirements for Percutaneous Valve Repair and Replacement Credentialing Criteria for Surgeons to Perform Transcatheter Aortic Valve Implantation (TAVI) Registries

37 Alternative Methodology for Surveillance of Drug-Device Safety Paul the Octopus FACC deceased

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