Medpace Director of Clinical Operations Mainfong Ang, presented a current view of best practices in Asia at the Global Engage conference, May 2013

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Opportunities and Challenges of Managing
Clinical Trials in Asia
Mainfong Ang
Director, Clinical Operations

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Agenda
o Introduction
o Operational and Logistical aspects of running
trials in Asia
o Challenges and advantages of various Asian
countries
o Best practices to get most from the sites
o Special consideration of oncology programs

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Demography
www.clinicaltrial.gov (as of 23Apr2013)

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FDA inspection (1/Oct/2008 – 30/Sep/2012)
o Conducted by Centre for Drug Evaluation and
Research (for bio-monitoring)
Country Total NAI VAI OAI %NAI
US 1078 583 430 65 54
UK 19 7 12 0 37
Canada 27 16 11 0
59
China 11 6 5 0 54
KR 8 4 4 0 50
TW 3 2 1 0 66
*NAI (no action indicated); VAI (voluntary action indicated); OAI (official action indicated)
Resource: http://www.fda.gov/iceci/enforcementactions/ucm222557.htm

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Number of Registered Clinical Trials
o Contribution from
Asia value in
Clinical trial
= 14.36 %
Region Name Number of Studies
World 143954
Africa 3245
Central America 1836
East Asia (Japan) 12521 (2677)
Europe 39018
Middle East 5862
North America 75001
North Asia 2677
Pacifica 3942
South America 4850
South Asia 2573
Southeast Asia 2903
www.clinicaltrial.gov (as of 23Apr2013)

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Key Milestone for Clinical Trials – Start-up
o Comparison of start-up timeline
Country IRB/REC
submission
Regulatory
submission
Total
duration
Paradigm
Hong Kong 4 – 8 weeks 12 – 16
weeks
16 – 24
Weeks
Parallel
China 4 – 12 weeks 36 – 48
weeks
44 – 96
weeks
Sequential
Korea,
Republic of
4 – 12 weeks 8 – 12
weeks
20 – 24
weeks
Parallel
Taiwan ROC 8 – 16
weeks
4 – 12
weeks
20 – 24
weeks
Parallel

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Key Milestone for Clinical Trials – Start-up
o Comparison of submission dossier (For IRB)
Country English
document
Local
language?
Site Budget GCP
certificate
Hong Kong Yes Yes No No
China N/A Yes Yes (some) No
Korea,
Republic of
N/A Yes Yes Yes
Taiwan ROC N/A Yes No Yes

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Key Milestone for Clinical Trials – Start-up
o Comparison of submission dossier (For
competent agency)
Country English
document
Local
language?
Site Budget
Hong Kong Yes Yes No
China No Yes No
Korea,
Republic of
No Yes No
Taiwan ROC No Yes No

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Key Milestone for Clinical Trials – Start-up
o Special requirements during application
Country Special Requirements
Hong
Kong
Sample drug; Import license for biological materials (e.g.
tumor block)
Korea,
Republic
of
Import license for lab kits
Taiwan
ROC
Import license for lab kits

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Operational Consideration - Korea
o Source documentation and monitoring
• National Health Information System (NHIS) – electronic
medical record (EMR) legalized in 2003.
• Mainly written in Korean
• Study monitor -specific account available for
monitoring purpose
• Interpreter would be needed if the study monitor
cannot read Korean

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Operational Consideration - Korea
Login page of eMR (Asan Medical Center)

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Operational Consideration – Hong Kong
o Source documentation and monitoring
• CMS, termed as Clinical Management Systems, is
accessible by clinical users at 43 hospitals and 120 clinics
since 1994.
• Investigator and CRCs at HA hospitals are accessible to
the subject clinical data, except those from private sector.
• English is used for official documentation throughout the
system
• As of today, both electronic and paper medical record
are used.
– OP notes will be printed and signed by the responsible
physician for archive.
– Consideration of 21 CRF part 11 compliance
• Monitor has no access to CMS and source data
verification (SDV) will be conducted over paper
documents.

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Operational Consideration – Hong Kong

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Operational Consideration - China
o Source documentation and monitoring
• Use of eMR for source documentation varies between
hospitals
– Direct data entry to system
– Scanning of hand-written electronic medical document
• No networked eMR is used in China
– Original medical record still replies on referral letter
• Retrieval of original medical could be limited to
litigation or other legal issues.
• Written in Simplified Chinese
• Interpreter would be needed if the study monitor
cannot read Simplified Chinese

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Operational Consideration – Taiwan
o Source documentation and monitoring
• eMR is also used. (need data on the popularity from
Taiwan)
• Traditional Chinese is used for official documentation
throughout the system
• As of today, both electronic and paper medical record
are used.
– Consideration of 21 CRF part 11 incompliance
• Monitor has no access to CMS and source data
verification (SDV) will be conducted over paper
documents.

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Operational Consideration – Safety
Reporting
o Timeline to notify IRB
Country Local
SAE
(death/ life-
threatening
event)
Overseas
SAE
(death/ life-
threatening
event)
Local
SAE
Overseas
SAE
Hong Kong 15 days 30 days 15 days 30 days
China 24 hours Not specified 24 hours Not specified
Korea,
Republic of
7 days 7 days 7 days 15 days
Taiwan ROC 15 days 7 days 15 days 15 days

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Operational Consideration – Safety Reporting
o Timeline to notify competent authority (CA)
Country Local
SAE
(death/ life-
threatening
event)
Overseas
SAE
(death/ life-
threatening
event)
Local
SAE
Overseas
SAE
Hong Kong 7 days (for
unexpected
events)
No
requirement
15 days (for
unexpected
events)
No
requirement
China 24 hours 7 days 24 hours 15 days
Korea,
Republic of
Not
specified/
annually
7 days Not
specified/
annually
15 days
Taiwan ROC 7 days 7 days 15 days 15 days

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Logistical Consideration in Clinical Supplies
o Local drug procurement may be necessary
because some treatment drugs are not
considered SOC or unavailable at site.
 To confirm drug supplies at the time of feasibility
 Local sourcing for drug supplies and shipment
o IP management/ disposal policy within the
country
 For cytotoxic drugs

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Logistical Consideration in Medical
Equipment and Specimen Management
o Supply of clinical facilities
 -80°C Freezer/ centrifuge may not be available at site
 Application of import license for lab kits (Taiwan and
Korea)
o Lab specimen shipment
 Consider application of export license for infectious
specimen & import for returned tumor block

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Challenges – Treatment Diversity
o Most countries follow international standard, but
may also adopt local consideration
 E.g. Choice of chemotherapy regimen which suits
Asian clinical profile
• Breast cancer: choice of anthracycline: epirubicin over
doxorubicin in Taiwan
• For further input from Medical advisor
• Differences in the understanding of medication
procedures due to differences in principles/clinical
guidelines and systems of out-patient operations

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Challenges – Treatment Diversity
o Dose calculation
 Maximum dose is too high for Asian patients in some
oncology studies.
o Use of herbal medicine
 The use is commonly found in China. It brings safety-
benefit issue to the trial subject

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Challenges – Language Barrier
o Translation
 China, Korea and Taiwan requires translation on
essential documents (e.g. protocol, investigator’s
brochure)
 Timeline is affected if amendment appears
o Data management
 Inaccurate coding/ translation of symptoms
• Incorrect interpretation
• DCF generation

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Challenges – Local Clinical Practice
o Patient compliance
 Lost-to-FU is frequent in China
o Obtaining informed consent
 Elder patients may not aware of their medical
conditions, which is chosen not to be disclosed by
their relatives
o Necessity of face-to-face meeting
 The practice is appreciated at the early stage, e.g.
site identification, feasibility

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Best Practices to Maximize Your Work
o Efficient feasibility/ site evaluation
 Seek regional KOL advice/ seek medical advisory
 Flexibility in protocol design
 Site staff resource and CRC
 Source document and eMR
 Paradigm of study payment
 Accurate and timely patient transportation fee
 Clarification of IRB responsibilities and procedures
 Use of government certified institution

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Best Practices to Maximize Your Work

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Best Practices to Maximize Your Work
o Project planning and management
 To balance global goal and standardized way with
local requirements and optimization
 To standardize procedures for diversified operations
 Levels of operations
• Core: protocol, adjunction procedures, central lab
• Regional: Monitoring procedures, ICF preparation (e.g.
data privacy ordinance), site budget
• Local: institutional requirements, local business practices

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Best Practices to Maximize Your Work

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Best Practices to Maximize Your Work
o Project planning and management
 Use of CRO and SMO
• To ensure sponsor governance and study oversight.
• Blooming use of SMO which provides various services in
CRC management, contract and budget & SOP review

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Best Practices to Maximize Your Work
Global Lead/ Sponsor
Regional operations Regional operations Regional operations
Local Local Local Local Local Local

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Special Consideration for Oncology
o National insurance coverage varies between
countries, which reflects on the feasibility
assessment, budget and patient recruitment in the
future.
 E.g. Prerequisite 1st line treatment for inclusion may not be
available at site/ in country practice. (use of small
molecule inhibitor for HCC in Taiwan)
o Consideration of lab sample
 selection of regional central lab to provide lab support for
the region
• genetic characterization for specific NSCLC, breast
cancer
 Clear communication about turnaround time
 The need to re-import the remaining tumor tissue

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Q&A