CLI and Device Intervention Across the Pacific – An FDA View Kenneth J. Cavanaugh Jr., Ph.D. Chief, Vascular Surgery Devices Branch Division of Cardiovascular Devices Office of Device Evaluation U.S. Food and Drug Administration CRT 2013 February 25, 2013 – Washington, DC

Disclosures Nothing to disclose

Device Regulation - General Challenge Balancing need to bring safe and effective devices to market as quickly as possible… …while ensuring that devices on the market remain safe and effective

Peripheral Vascular Disease: Complex and Diverse Anatomic locations Iliac Femoral Disease Claudication Critical limb ischemia (CLI) Use of adjunctive devices Balloons Atherectomy Embolic protection Popliteal Tibial

Other Challenges Smaller treated patient population than cardiac/coronary disease In the US, clinical equipoise often does not exist Many investigational devices available to physicians outside of clinical study Result: Clinical trials often slow to initiate and enroll

One Solution: Promote global development of clinical evidence designed to improve treatment options and strategies for peripheral vascular disease

Why the US and Japan? Large markets Strict regulatory systems Comparable levels of clinical care

US-Japan Global Clinical Trials May facilitate more timely and cost-effective introduction of new devices in both countries Reduction of redundancies in time and cost Simultaneous enrollment in both countries Ability to pool patients may reduce the total number of patients needed compared to that of two separate trials

Global Clinical Trial Challenges Poolability of patient data Demographics Clinical practice patterns Differences in trial infrastructure and regulations Site recruitment Monitoring Cost per patient ?

Critical Limb Ischemia (CLI) Patients with CLI represent a vulnerable and underserved population in both countries US and Japanese interest in exploring similarities/differences in CLI treatment Practice patterns Patient characteristics Criteria for successful treatment

Goals for CLI Facilitation and dissemination of single-protocol study paradigms for CLI A “true” single-protocol study may be challenging Identify areas where convergence is less probable Likely not a single protocol that applies to all potential CLI therapies Drug-coated stent ≠ atherectomy

Peripheral Academic Research Consortium (PARC) Develop consensus definitions/terms Promote improved clinical study designs Communicate and involve interested stakeholders Significant Japanese involvement Regulators, academia, industry PARC will facilitate conduct and interpretation of peripheral vascular studies worldwide

Other Areas of Potential Collaboration Stent fracture/imaging Causes Clinical consequences Peripheral vascular data registries Pre-market Post-market

Other Academic CLI Topics Role of imaging Technical limitations? Clinical value/need? Surrogate Endpoints Identify standardized, validated assessment method for wound healing? Role of tissue perfusion pressure Your ideas…?

Pre-Submission Process Highly recommend soliciting FDA feedback on global study designs/strategies prior to study initiation Differences in demographics, clinical practice, etc. Endpoint identification Follow-up duration Sample size Eligibility criteria

Summary Clinical evaluation of peripheral vascular devices involves unique scientific and regulatory challenges FDA strongly supportive of US-Japanese collaborative efforts and clinical study designs Several projects moving forward that will facilitate clinical evaluation and data analysis in the US and Japan Take advantage of FDA’s willingness to consider and discuss global strategies early in the process

Thank You!