Technologies and regulatory standards facilitate clinical trial globalization and mutual acceptance of clinical trial data. Changes in trial execution, however, are not 1:1 reflected in foreign data acceptance. Factors such as ethnic and local requirements seem to outweigh the benefits.

1. GLOBALIZATION OF CLINICAL TRIALS:
MUTUAL RECOGNITION OF CLINICAL STUDY RESULTS
Annet Muetstege| CTMD, 21 September 2016

2. Change in Clinical Trial distribution
• Proportion of clinical trials in the US down ~18%
• Proportion of trials in EU up ~9%
• Proportion of trials in Japan up ~7%
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George M et al. Current Clinical Pharmacology, 8, 115-123, 2013

3. Why use foreign data?
Limit redundant duplication
• Resources - companies and regulators
• Ethics – study participants
Faster access to innovative care
• Subject recruitment
• Less studies
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4. Clinical Trial execution - GCPs
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5. GCP consistency
GCPs becoming alike
• Rights, safety, welfare of trial participants
• Scientific integrity of trial methods
• Accuracy of data
• Reliability as a basis for RA decision making
Non substantive/ administrative differences exist
• Financial disclosure, IRB/ EC requirements, …
• Take into account
ISO 14155 – acknowledged as standard for medical device studies
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RAPS regulatoryfocus. January 2013

6. ISO 14155:2011
2015-Mar-26 IMDRF Statement on Use of
ISO 14155:2011
• Acknowledged by main regions can serve as
global standard to medical device GCP’s
Facilitates acceptance medical device
foreign data
Not specifically address mutual acceptance
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7. ICH harmonised guidelines - medicine
ICH E5 - Ethnic factors in the acceptability of
foreign clinical data
• the characteristics of foreign clinical data and the regulatory
strategies to minimize duplication of clinical data and facilitate
acceptance of foreign clinical data in a new region
• the use of bridging studies, when necessary, to allow extrapolation
of foreign clinical data to a new region
A clinical study in the new region to provide information on the
pharmacodynamics or clinical safety, efficacy, dosage and dose regimen in
the new region
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8. Standards on foreign data – devices
US/ FDA
• March 2001 – Guidance for Industry - Acceptance of Foreign
Clinical Studies
• April 2015 – Draft guidance Acceptance of Medical Device Clinical
Data from Studies Conducted Outside the US
Japan
• March 1997/ 2006 - MHW 479: Handling of data of clinical studies
for medical devices conducted in foreign countries
Europe
• June 2016 - MEDDEV 2.7/1 revision 4
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9. Requirements in brief
United States/ Japan/ Europe
1. Clinical studies in conformance with international
standards, such as Declaration of Helsinki, GCP, and
ISO 14155
2. Clinical data on the applicable study population and
clinical condition
3. Methodology should meet local standards, including
scientific appraisal
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10. Challenges with foreign data
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Dunder. Issues on Acceptance of Foreign Clinical Data in Europe from a Regulatory Perspective.

11. Medical devices?
■ Anatomy
■ Constitution
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12. Racial skin differences
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DuPlesis. Dissertation. 2012

13. Aspects on comparability
Clinical study population
• General charateristics (genetic, phenotypic)
• Confounding clinical conditions
Clinical study methodology
• Local standard of care – comparator group
• Performance/ effectiveness - endpoints
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14. Origin PMDA Clinical Data
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https://www.pmda.go.jp/english/about-pmda/0004.html#clinicaldata
■ Acceptance of sole foreign data substantial ~60%
■ Decreased contribution of Japanse clinical data
0
20
40
60
80
100
2006 2007 2008 2009 2010 2011
ProportionofClinicalTrials
Time period
Origin PMDA clinical data
Japan only Japan + foreign Foreign only

15. Origin PMA Clinical Data
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■ Acceptance of foreign data increased ~4%
■ > 60% US data only
0
20
40
60
80
100
M,J,J 2001 M,J,J 2006 M,J,J 2011 M,J,J 2016
ProportionofClinicalTrials
Time period
Origin PMA Safety & Effectiveness data
US only US+OUS OUS only
Muetstege. Personal analysis. 2016

16. What about Europe?
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■ Applicability rather than origin
■ Local implementation after CE-mark often requires additional
post-market studies

17. Conclusion
• The clinical trial as well regulatory environments
favor mutual use of clinical data
■ Electronic means, standards
• Changes in clinical trial execution are not
reflected in similar developments in foreign
clinical data acceptance
• Other factors seem to outweigh the benefits
■ Population differences, local requirements/ standards
• Medical device bridging studies
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18. 18
Questions?
Applied Clinical Services BV
Annet.muetstege@appliedclinicalservices.com