1. 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

2. Disclosures
Nothing to disclose

3. 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

4. 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

5. 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

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

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

8. 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

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

10. 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

11. 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

12. 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

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

14. 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…?

15. 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

16. 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

17. Thank You!