Are RCT always needed: Experience with objective performance criteria (OPC)

Transcription

1 Are RCT always needed: Experience with objective performance criteria (OPC) Peter A. Schneider, MD Krishna Rocha-Singh, MD Kaiser Foundation Hospital Honolulu, Hawaii Prarie Heart Institute Springfield, Illinois

2 Disclosure Peter A. Schneider... I have the following potential conflicts of interest to report: Scientific Advisory Board (non-paid): Cardinal, Abbott, Medtronic Royalty (modest): Cook Co-founder and Chief Medical Officer: Intact, Cagent

3 Challenges with RCTs Enrollment time Enrollment bias Ethical issues Technology out of date Technology not fully developed

4 RCTs That Helped to Shape the Field AAA: EVAR, DREAM > OPC-like safety goals Renovascular: CORAL > killed the procedure Carotid: CREST > in process SFA stents: OPCs SFA DCB: Levant 2, IN.PACT SFA > in process BTK > in process

5 Optimal Performance Goal Symptomatic Carotid Stenosis Trial No. 30 day stroke/ death rate EVA-3S % 10 SPACE % 38 ICSS % 33 CREST % 42 Events OPG % ( %) 124 Weighted mean for perioperative stroke and death for CEA in patients with symptomatic carotid stenosis

6 PTA control arm from 3 randomized, industry- sponsored device trials Rutherford Category 2-4 Femoral-popliteal lesions (4 cm 15 cm) 12 month duplex follow-up Results combined with a survey of medical literature from

7 Results of Femoral-popliteal PTA Industry sponsored N =116 Lesion length = 8.7 cm 12-month duplex patency = 28% Medical literature N = 191 Lesion length = 8.9 cm 12-month duplex patency = 38%

8 Challenges with OPC Access to data Populations not poolable Superiority more difficult to prove Temporal improvement in other factors may cause bias in favor of the treatment group (eg; more aggressive use of DUAP)

9 A Slide from VIVA 2007: Use of the VIVA Performance Goals and Definitions will HOPEFULLY: Encourage industry to initiate larger, robust registries of nitinol stenting in claudicants Promote uniform reporting standards and endpoint assessment (i.e., stent fracture assessment, DUS definitions, etc.) Represent renewed collaboration between physicians, the FDA and industry! Provide the foundation for the development of a nitinol stent OPC

10 Six Adjudicated Patient Level Data Sets of 999 RC 2-4 Claudicants with Atherosclerotic FP Occlusive Disease Trial A Trial B Trial C Trial D Trial E Trial F Overall Summary of Baseline Data and Primary Patency Courtesy: Krishna Rocha-Singh, MD

11 Primary Patency, ABI, Lesion Length, and CD-TLR at 12-mos Effects of Patient Characteristics on Outcomes Multivariable Models

12 Binary Patency vs. CD-TLR as a Function of Lesion Length at 12-mos Patency and TLR Results by Lesion Tertile

13 Binary Patency, Lesion Lesion, CD- TLR and Pre-Procedure ABI at 12- mos Outcomes by Patient Risk Groups

14 VIVA SFA Nitinol Stent OPC: Access to robust, de-identified, independently adjudicated, patient level data from SFA nitinol SFA trials provides important insights into the ideal patient cohort who benefit from nitinol stenting through 12-mos follow-up Additional analyses correlating stent-related surrogates (i.e., absolute PVS) with clinical outcomes (CD-TLR) may allow for the evolution to more sensitive primary endpoints in both SFA stents and newer non-stent therapies.

15 Pat ient s required How many patients needed per group to show a difference in limb salvage between devices? Pow er Calculation Clinical success per group 713 per group per group 80% Power Clinical success 85% n1=n2 Alpha= per group 110 per group One Year Freedom from Am put ation Assumes 85% one year limb salvage rate for tibial angioplasty in CLI

16 Tibial Bypass: SVS Optimal Performance Goals Conte et al. Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc Surg 2009;50:1462

17 Percent Event-Free Survival XCELL Limb Salvage Trial Kaplan-Meier 12 Month Freedom from All Cause Death or Major Amputation by Baseline Rutherford Criteria Rutherford 4 Rutherford 5 Rutherford XCELL Trial Days CC&I 2011

18 Summary of Efficacy Outcomes Outcome Compared to Surgical OPG* Number of Events 1 year event free (%; 95% CI) Efficacy OPG (%)* Efficacy OPG Achieved? MALE + POD ( ) 71 Yes AFS ( ) 71 No RAS ( ) 39 No RAO 48** 43.7 ( ) 55 No Limb Salvage ( ) 84 No Survival ( ) 80 No MALE (major adverse limb event); POD (perioperative death); AFS (amputationfree survival); RAS (any reintervention, above ankle amputation of the index limb, or stenosis); RAO (any reintervention or above ankle amputation of the index limb). The lower bound of the 95% Confidence Interval must be the OPG. **The last RAO event occurred at 399 days. *Conte et al. J Vasc Surg 2009;50:

19 Experience With Objective Performance Criteria Experience is growing in each of the vascular beds with objective performance criteria. Significant advantages over RCTs. Some disadvantages Could actually be used to identify areas where RCTs are appropriate.

20 Are RCT always needed: Experience with objective performance criteria (OPC) Peter A. Schneider, MD Krishna Rocha-Singh, MD Kaiser Foundation Hospital Honolulu, Hawaii Prarie Heart Institute Springfield, Illinois