conducting clinical trials in asia: global engage.may.2013

FOCUSED. TRUSTED. GLOBAL.

Opportunities and Challenges of Managing Clinical Trials in Asia

Mainfong AngDirector, Clinical Operations


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Agenda

o Introductiono Operational and Logistical aspects of running

trials in Asiao Challenges and advantages of various Asian

countrieso Best practices to get most from the siteso Special consideration of oncology programs


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Demography

www.clinicaltrial.gov (as of 23Apr2013)

http://www.clinicaltrial.gov/


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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 54UK 19 7 12 0 37Canada 27 16 11 0

59China 11 6 5 0 54KR 8 4 4 0 50TW 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

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)

http://www.clinicaltrial.gov/


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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 – 24Weeks

Parallel

China 4 – 12 weeks 36 – 48weeks

44 – 96weeks

Sequential

Korea, Republic of

4 – 12 weeks 8 – 12weeks

20 – 24weeks

Parallel

Taiwan ROC 8 – 16 weeks

4 – 12weeks

20 – 24weeks

Parallel


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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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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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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 IRBCountry 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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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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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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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


Q&A

conducting clinical trials in asia: global engage.may.2013

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