1. Japan-USA Synergies: Academic View
Mitchell W. Krucoff, MD, FACC
Professor, Medicine/Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit
Duke Clinical Research Institute

2. Mitchell W. Krucoff, MD DISCLOSURES Consulting Fees
Biosensors International, Terumo Medical Corporation
Grants/Contracted Research
Boston Scientific Corporation, Medtronic CardioVascular, Inc.
Honoraria
Abbott Vascular, Cordis, a Johnson & Johnson company

3. Clinical Evaluation of New Medical Devices
Global Clinical Evaluation
Clinical Evaluation of New Medical Devices
Iceland
Norway
Finland
Russia
Estonia
Canada
U.K.
Denmark
Latvia
Ireland
Netherlands
Poland
Lithuania
Germany
Belgium
China
Czech Rep.
Switz.
Austria
Slovenia
Ukraine
France
Hungary
Romania
Italy
Bulgaria
Georgia
Spain
United States
Portugal
Greece
Turkey
Japan
Israel
Egypt
Mexico
United Arab Emirates
Taiwan
Dominica
India
Hong Kong
Redundancy
Guatemala
Panama
Thailand
El Salvador
Venezuela
Malaysia
Columbia
Singapore
Indonesia
Added Cost
Brazil
Paraguay
Australia
Chile
Time Delay
South Africa
Uruguay
Argentina
New Zealand
Less Information
October 2002

4. Perceptions of a Japan-USA Trial
Synergies
Complementary clinical practice patterns
Integrated not interlocked informative trials
Growing interest levels:
Patients
Academics
Regulators
Industry
Media
Risks connecting two markets
Interlocked timelines
Interlocked regulatory steps
Added risks and cost
Departure from traditional corporate global plan “silos”

5. “Harmonization By Doing” Japan-USA Program
MHLW-PMDA
“Harmonization By Doing” Japan-USA Program
Professional Societies
Medical Industry

7. Proof of Concept: DES The Regulatory Landscape in Japan and USA
New DES Guidance in USA
Some angiographic follow up
Clinical follow up separately, or accounting for impact of protocol angiography
New Paradigms in Japan
More GCP capable sites
Faster trial enrollment
First DES RCT

8. Proof of Concept: DES The Clinical Trial Landscape Japan and USA
Fewer sites overall
Good and bad quality sites
More expensive per pt
Follow up is routine cath clinical practice
USA
Many sites
Good and bad quality sites
Fairly expensive per pt
Follow up cath is protocol
“active control” study less efficient enrollment
More lost to follow up
“Occulostenotic” events

9. Proof of Concept: DES Integrated (NOT Interlocked) Studies Design
Japan
Multicenter RCT
Per clinical practice: primary angiographic outcome
100% angio follow up
Some USA sites
Addl safety info from pivotal USA study
USA
Multicenter RCT
Per clinical practice: primary non-angio clinical outcome
No protocol angiography
Some Japanese sites
Angio f/u info from pivotal Japan study
concomitant enrollment, or
“Japan first” design
Japan-USA study leadership, CEC, DSMC opportunities

10. Proof of Concept: DES What it would take?
Prospective SAP for each: Shonin and PMA
Model justifying relevance of angio & clinical observations between human subjects in Japan and USA
Dialogue across MHLW/PMDA and FDA

11. Proof of Concept: DES What It Could Deliver
Individual, flexible Japan and USA filing timelines
1-3 years acceleration of approval times
Better overall safety and effectiveness data
Potentially “Japan first” scenario
Integrated post-market landscape

12. Japan-USA Synergies: Academic View
Mitchell W. Krucoff, MD, FACC
Professor, Medicine/Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit
Duke Clinical Research Institute