MANAGING CLINICAL TRIALS OUTSIDE OF THE US
John Potthoff, PhD
President & CEO
Theorem Clinical Research
Global, full-service CRO
• 1000+ employees
Planning and execution of clinical trials and regulatory
applications
Focused business units:
• Medical Device and Diagnostics
• BioPharmaceutical Development
• Clinical Analytics
Coverage of 44 countries
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Why conduct trials outside of the US?
Gain registration in target company
Support a global development effort
Complex or rare diseases; incident rates may not be high enough in
the US to enroll a trial
Timelines for registration may be faster outside of the US to allow a
company to begin sales while completing registration in the US
Costs may be reduced for registration outside of the US
Competitive landscape may be advantageous outside the US
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Where are trials conducted?
Data as of 02 December 2012
Page 4
Actively Recruiting Studies
(Data as of December 02, 2012)
Non-U.S. Only (49%)
U.S. Only (45%)
Both U.S. & Non-U.S. (7%)
Location
Number of Recruiting Studies and
Percentage of Total
Non-U.S. Only
14,193 (49%)
U.S. Only
13,010 (45%)
Both U.S. & Non-U.S.
1,898 (7%)
Total
29,101
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Focus on Asia Pacific
Aging
Population
Increasing Life
Expectancy
Increasing
Incidence of
Major
Disease
Increasing
Health
Consciousness
Higher
Disposable
Income
Over 30% of new expenditures on healthcare worldwide are attributable to Asia.
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• Population
exceeds 4
billion and is
genetically
diverse
• High
incidence of
some
indications:
Diabetes
Mellitus
(> 11%),
Hepatitis B,
etc.
• Ability to
recruit patient
naïve and
advanced
case patients
Seasonality
• Start-up
timelines
have become
more
favorable
(other than
China) and
are 4-6
months
covering all
applications,
site selection,
contract
negotiations,
etc.
Resources
• Cost of
clinical trials
in Asia is
much lower
than in
US/EU
(30-50%)
Time
Money
Why Asia for Clinical trials?
• Southeast
Asia:
Advantage for
seasonal
indications
(e.g.
influenza)
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Regulatory Authorities in Asia Pacific
Country
Authority
China
SFDA
Hong Kong
DoH
Australia
TGA
India
DCGI
Japan
MHLW
Korea
KFDA
Malaysia
MoH
New Zealand
Medsafe
Philippines
BFAD
Singapore
HSA & AVA
Taiwan
DoH
Page 8
Asia Regulatory and Start-up Timelines
KEY ITEMS:
Regulatory
Regulatory and Ethics
Ethics
in parallel
Regulatory Ethics
Ethics
Subm ission preparation tim e
Site Contract negotiation and signature
Weeks
Prep. w 1
New Zealand
4w
w2
w3
w4
w5
w6
w7
w8
Regulatory follow ed by Ethics
RegulatoryEthics follow ed by Regulatory
w9
Im port license application and custom s clearance
First SIV
w 10 w 11 w 12 w 13 w 14 w 15 w 16 w 17 w 18 w 19 w 20 w 21 w 22 w 23 w 24 w 25+
+
7 w eeks
8-12 w eeks
1-2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
2-3 w eeks
Australia
12-16 w eeks
4w
2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
1-2 w eeks
2 w eeks
China
8w
8-10 m onths
"+"
4-8w eeks
1-2 w eeks
2 w eeks
Malaysia
4w
4-8 w eeks
6-8 Weeks
1-2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
4-8 w eeks for issue of im port license
2 w eeks
Philippines
4w
8-12 w eeks
8-12 Weeks
1-2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
6-8 w eeks
South Korea
4w
8-12 w eeks
2-8 w eeks (Som e ECs require CA approval letter)
1-2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
8-12 w eeks for issue of im port license
Taiw an
4w
1 w eek
Complicated
and risk of
delays
8-12 w eeks
8-12 w eeks
1-2 w eeks
Contract sign off w ithin 1-2 w eeks after EC approval
8-12 w eeks for issue of im port license
*Note: China not to scale
2 w eeks
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Data Collection in Asia Pacific
Virtually all sites
conduct clinical
research in English
Most Trials
conducted in
accordance with
global regulatory
guidelines*
*Some local trials
conducted according to
local minimal guidelines
Virtually all sites can
work in electronic
data capture (EDC)
systems
Data
Collection
Most of the leading
EDC tools now allow
for multi-language
data processing,
allowing sites to add
comments in their
local language**
**Requires ability of CRO
to process data in local
languages
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China
Focus on China and India
*1.3 billion people
*537 active trials in
oncology (cancer)
*102 active
medical device
trials
*1.2 billion people
*124 active trials in
oncology (cancer)
*27 active medical
device trials
India
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Drug Controller General of India (DCGI)
Currently politicizing on
policy issues relating to
compensation for injury to
or death of a participant in
a clinical trial
Unable to conduct first-inman trials in India
Only may conduct trials in
India if registration in India
is the goal
Currently left to the
discretion of the
Ethics Committee
Indication under
investigation/cause
of injury or death
may not be
considered
Example: Oncology
trials often have
survival as the
outcome measure
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Conclusions
Conducting clinical trials outside of the US is a
necessary part of reaching a global audience
Conducting clinical trials outside of the US can be highly
complex without local knowledge and experience
Several advantages to conducting trials outside of US:
• Registration in multiple regions
• Access to specific patient populations
• Strategy to seek registration in cost advantaged
locations
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John Potthoff, PhD
President & CEO
john.potthoff@theoremclinical.com
512-734-1715