globalization of clinical trials: mutual acceptance of medical device data

GLOBALIZATION OF CLINICAL TRIALS: MUTUAL RECOGNITION OF CLINICAL STUDY RESULTS

Annet Muetstege| CTMD, 21 September 2016

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%

CTMD, 21-Sep-2016 ACS Globalization Clinical Trials 2

George M et al. Current Clinical Pharmacology, 8, 115-123, 2013

Why use foreign data?

�Limit redundant duplication

• Resources - companies and regulators

• Ethics – study participants

�Faster access to innovative care

• Subject recruitment

• Less studies


Clinical Trial execution - GCPs


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


RAPS regulatoryfocus. January 2013

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


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


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• April 2015 – Draft guidance Acceptance of Medical Device Clinical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


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


Challenges with foreign data


Dunder. Issues on Acceptance of Foreign Clinical Data in Europe from a Regulatory Perspective.

Medical devices?

■ Anatomy■ Constitution


Racial skin differences


DuPlesis. Dissertation. 2012

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


Origin PMDA Clinical Data


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

Pro

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ica

l Tri

als

Time period

Origin PMDA clinical data

Japan only Japan + foreign Foreign only

Origin PMA Clinical Data


■ 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

Pro

po

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n o

f Cli

nic

al T

ria

ls

Time period

Origin PMA Safety & Effectiveness data

US only US+OUS OUS only

Muetstege. Personal analysis. 2016

What about Europe?


■ Applicability rather than origin■ Local implementation after CE-mark often requires additional

post-market studies

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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Questions?

Applied Clinical Services [email protected]

globalization of clinical trials: mutual acceptance of medical device data

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