1. Building Synergy Between US and Japan DES Clinical Trial Designs: FDA View
Erica Takai, PhD for Andrew Farb, M.D.
Interventional Cardiology Devices Branch, Division of Cardiovascular Devices, U.S. FDA/CDRH

2. Erica Takai DISCLOSURES
I have no real or apparent conflicts of interest to report.

3. Global Trials and OUS Data Current FDA Perspective
OUS studies often used to provide initial safety and effectiveness data to support initiation of a pivotal IDE study
FDA is increasingly being asked to review global trials
Studies performed solely OUS may be considered for the PMA

4. Challenges to the Regulatory Review of OUS Studies
Protocols missing essential elements
Study endpoints
Detailed inclusion/exclusion criteria
Subject follow-up schedule
Lack of independent CEC’s DSMB’s, and core labs
Inadequate monitoring of source documentation and accounting of protocol deviations
Absence of long-term follow-up beyond the primary endpoint
Requirement that OUS study results are applicable to a US population

5. Data Pooling Considerations
Baseline demographic characteristics
Cardiac risk factors
Presenting symptoms
Practice of medicine factors
Diagnostic testing
Procedural equipment and techniques
Thresholds for hospitalization and treatment
Medication availability and use
Potential differences in disease pathophysiology based on genetic factors

6. Assessing Heterogeneity in Data Analysis
When evaluating clinical outcomes, demonstrate homogeneity of demographic and procedural covariates across different patient subgroups
Evaluate the interaction between treatment and patient subgroup (e.g., treatment by patient population)
If there is significant qualitative interaction, data poolability is problematic and study interpretation may be difficult

7. Building Synergy Between US and Japan: DES Clinical Trials
DES clinical trials offer a good opportunity to take advantage of Global Harmonization efforts
Well-characterized disease risk factors, pathophysiology, and clinical manifestations
Well-established trial endpoints
Fairly mature field with approved first and second generation devices

8. Building Synergy Between US and Japan: DES Clinical Trials
Consider novel trial designs maximizing strengths of each system
Critically important mechanistic insights from baseline and follow-up imaging studies: Angio, IVUS, OCT
Use available data to show that vascular biologic responses are similar between both populations
Collection of stent fracture data
Pivotal studies with clinical endpoints only with appropriate evaluation for heterogeneity
Avoids introduction of confounders associated with protocol-required follow-up imaging (OSR)

9. Building Synergy Between US and Japan
DES clinical trial development well-positioned to be part of CDRH’s 2010 Strategic Priorities…

10. Priority 1. Fully implement a total product life cycle approach
Strengthen our efforts to address changes in the global-market landscape
Improve the coordination of international activities across CDRH.
Associate Director for International Affairs
Develop mechanisms to exchange and make better use of medical device information with trusted foreign authorities.
GMP inspections

11. Contact Information
Interventional Cardiology Devices Branch
(301)