Use of Registry Data for Post Market Device Surveillance: IOM Presentation

Transcription

1 Use of Registry Data for Post Market Device Surveillance: IOM Presentation Eric D. Peterson, MD, MPH Professor of Medicine Vice Chair of Quality, Dept of Medicine Director of CV Research Duke Clinical Research Institute (DCRI) Author Disclosure:

2 Wonders of Modern Cardiac Devices Heart valves Pacemakers / AICDs Coronary Stents Vascular Closure Devices Vein Graft Harvest Devices LVADS

3 Fears of Modern CV Devices Bjork-Shiley Strut Fractures Pacemaker Recalls ACID failures Late Stent Thrombosis AAA endograft ruptures LVAD save lives but... In REMATCH Line sepsis: 42% Device failure: 35%

4 Evidence-based Device Selection. Premarket evaluation Often via 510K process, limited RCTs Once on market, we face. Rare events not seen in pre-market evaluation become apparent with increased n Possible downstream safety issues Use in wider array of high-risk patients Off Label ( expanded ) use Device-drug interaction (e.g., stent/adp inhibitors) MD---device issues ( the learning curve )

5 FDA Device Frustrations Rapid evolution of technology can make studies obsolete Industry lacks incentive or ability to conduct quality PMS Clinical community and public that often does not demand evidence or support studies And just want access

6 Clinical Registries: Can They Help? Creative Sentinel system to track devices once on market. System could: Community level system to Provide denominator for use Gather data on off-label use Alert potential device safety issues Overall class, manufacturer specific Broad patient subgroups

7 Clinical Device Registries: Options Manufacturer-specific Device Registry eg. Medtronic pacer registry Multi-sponsor Device Registry eg. LVAD (IMACS), AAA endografts Data from RCTs Existing Procedure/Disease Registries eg. STS, ACC, MassDac Directly from EHR. once adopted/interoperable

8 US CV Clinical Registries Society of Thoracic Surgery: 900+ centers Coronary artery bypass surgery Valve surgery Congenital heart surgery Thoracic surgery National Cardiovascular Data Registry: Hospitals Cath/Percutaneous coronary intervention Implantable cardiac defibrillators (ICD) Acute coronary syndromes (ACS) Carotid stenting Ambulatory CV disease (launching) AHA-Get With The Guideline Program: hospitals Coronary artery disease (CAD) Heart failure Stroke Ambulatory module (launching)

9 Expanding Capacity and Use of Clinical Registries Clinical Registry Cross sectional Studies Clinical Registry Claims Data Longitudinal Evaluations Clinical Registry Detailed Pharm + Device Info Longitudinal Outcomes CER-Safety Surveillance Clinical Registry Device/Drug RCT Longitudinal Outcomes Practical Clinical Trials

10 Examples of FDA Partnership with Registries for Post Market Device Surveillance ACC Stents Closure Devices STS TMR Endovascular Harvesting AVR

11 Evolution of PCI Stent Technology Drug Eluting Stents: Cypher -Sirolimus (Bx Velocity)- Cordis /JJ Taxus -Paclitaxel (Express / Liberte) - Boston Scientific Endeavor - Zotorolimus (Driver) - Medtronic Xience -Everolimus (Vision) - Abbott Vascular/Guidant Next Generation Stents Cypher Elite sirolimus on new platform Taxus Liberte Endeavor Bioabsorable Polymer Bioabsorable Stents

12 Rapid Adoption of DES for On and Off Indication Use % 2.5% % U se % Mortality 2.0% 1.5% 1.0% % Qtr Qtr Qtr4 On-label Off-label* 0.0% On- Label ST MI ISR SVG CTO Off-Label Rao SV Am J Cardiol 2006;97:

13 Late Safety Concerns Raised for DES Percent Cumulative Incidence Rate DES+C DES-C DES+C BMS-C DES+C BMS+C BMS+C BMS-C DES-C BMS-C -Eisenstein et al. JAMA 2006 % (95% CI) -3.3 (-6.3, -0.3) -2.5 (-4.4, -0.6) -1.7 (-4.2, 0.8) -0.7 (-2.9, 1.4) 0.8 (-1.8, 3.5) Months p DES-C BMS-C BMS+C DES+C

14 Effect of Safety Concern on DES Use DES Debate Begins FDA Advisory Panel Roe M et al Circ CV Qual Outcomes, doi: /circoutcomes

15 ACC NCDR-AHRQ DEcIDE DES Analysis Objective: To examine comparative effectiveness and safety of DES vs BMS in a national PCI cohort Population: 262,700 NCDR PCI pts 1/04-12/06 Follow up: Link NCDR to CMS claims data using indirect identifiers Analysis: Inverse propensity weighted model 102 covariates; Cox PH to verify mortality

16 2008 ACC LBCT: NCDR DES and BMS 30-month Adjusted Rate / 100 patients BMS DES 0 Death MI Revasc Bleeding Stroke HR = 0.75 (0.73,0.77) HR = 0.76 (0.72,0.80) HR = 0.91 (0.89,0.94) HR = 0.91 (0.85,0.98) HR = 0.96 (0.88,1.04)

17 FDA-STS-DCRI TMR Registry Initiated by FDA Partnership: STS, academics, regulatory Goals: Characterize trends TMR use Evaluate acute safety Evaluate risk factors Evaluate device-operator interactions

18 Diffusion of TMR into Practice % Sites performing TMR % Total TMR procedures % TMR+CABG procedures % TMR only Cumulative proportion of STS sites performing TMR % TMR of total procedures Peterson E. JACC 2003;42:

19 TMR Outcomes Outcomes All TMR patients (n= 1850) TMR w/o CABG (n=448) TMR w/cabg (n=1402) In-hospital mortality day mortality Operative mortality Major morbidity and mortality* *Includes operative mortality, reoperation for any reason, deep sternal wound infection, renal failure, and prolonged ventilation Peterson E. JACC 2003;42:

20 FDA STS TMR Longitudinal Evaluation Underway Objective: Compare longterm clinical outcomes for two existing laser devices Study Design: Retrospective cohort Population: STS Data linked to CMS Outcomes: longitudinal major morbidity and mortality Methods: Inverse Probability Weighted (IPW) estimators and Cox PH Models

21 Endovascular Harvesting Which Leg Would You Want?

22 PREVENT-IV Study Design 3000 patients 1st CABG Edifoligide 30-day Adverse Events Placebo 1st 2400: 1-year Angiography 1, 2, 3, 4, 5-year follow-up Death, MI, Revascularization with VG failure

23 Distribution of EVH Across Sites Proportion of patients with EVH Site (each column represents one site) Lopes, RD et al N Engl J Med Jul 16;361(3):235-44

24 Vein Graft Failure 50% 45% 47% Endoscopic Open Vein Graft Failure 40% 35% 30% 25% 20% 15% 10% P< % 28% P< % 5% 0% Per Patient Per Graft Lopes, RD et al N Engl J Med Jul 16;361(3):

25 0.10 Mortality Proportion of patients with death EVH Open P = HR 1.52, 95%CI Number of patients at risk EVH Open Years from surgery Lopes, RD et al N Engl J Med Jul 16;361(3):235-44

26 FDA-STS Endoscopic Vein Harvesting Surveillance Study: Underway Objective: Compare post-approval clinical outcomes of 2 existing EVH devices Study Design: Retrospective Cohort Study Population: STS linked to CMS, Outcomes: Major Morbidity, Mortality, and MACE Methods: Inverse Probability Weighted (IPW) Estimators and Cox PH Models

27 Aortic Valve Replacement Valve Type Deterioration Thromboemboli Bioprostheses Mechanical

28 Aortic Valve Replacement

29 Duke AHRQ DEcIDE AVR Research Effort A Collaboration with the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery National Database

30 AHRQ Device Surveillance Clinical Effectiveness of AVR Prostheses Objectives: Evaluate clinical effectiveness and safety of marketed biologic versus mechanical aortic valve prostheses in older patients Examine CER and safety of specific valves in important patient subgroups Determine the optimal anticoagulant strategy for the prevention of early thromboembolic events following AVR in elderly patients

31 Bioprosthetic Valve Replacement Early Thromboembolic Risk st 3 Month 1 st Aspirin Warfarin RF+ Class I (B) Class I (C) RF - Class I (C) Class IIa (C)

32 Bioprostetic Valve Subtypes for AVR, STS Stented Pericardial Stented Porcine Stentless Porcine

33 Anticoagulants post-bvr Population

34 Anticoagulants post-bvr Preliminary Findings 3 months* RF (-)( Total Events Asp (n=7,009) Asp+War (n=2,056) Death Ischemic Stroke Hemorrhage RR (95% CI) 0.65 (0.44, 0.95) 0.37 (0.14, 0.96) 4.13 (2.62, 6.52) NNT/NNH (95% CI) 129 (72, 614) 217(129, 695) -45 (-30,( -85) *Adjusted Results

35 Aims New Directions: AHRQ ACC-STS CABG v PCI Study: ASCERT Using linked data, examine longterm outcomes and predictors of outcome for CABG and PCI. Compare longterm outcomes of multivessel CABG to PCI Overall Among key subgroups Determine the comparative effectiveness of CABG vs PCI after accounting for detailed angiographic information (SYNTAX score) Examine the cost effectiveness of CABG vs PCI

36 New Directions: NHLBI GO Grant National CV Research Infrastructure (NCRI) Aims Expand CV trials site investigator pool Facilitate data standards and interoperability Single entry for trials and registry Develop tools and training programs Investigator training Protocol development Trial infrastructure Create/Implement Clinical Trials Platform

37 Clinical Registries: Conclusions for Future Post-marketing device surveillance is and will remain a huge issue for healthcare. Clinicians need to be actively involved Demanding better devise data Identifying device issues Clinical registries provide novel solutions ed to allow for effective/efficient PMS!