2. Integrative Medicine
a combination of
mainstream medical therapies
and
Complementary and alternative medicine
(CAM)
for which there is high-quality scientific
evidence of safety and effectiveness
2
5. 新藥開發流程
臨床前研究
Submit NDA NDA Approval
Submit
IND
Chemistry and Physical Characterization
新藥審核
臨床試驗
Formulation
新藥監視
Scale-up
Botanicals with historical
documentation of safe human use
Phase II
Phase III
Phase IV
Pharmacology and Pharmacokinetics
Animal Safety Testing
12-24 months
1-4
month
9-12
months
6-18 months
12-24 months
中山醫學大學附設醫院中藥臨床試驗中心
8. Ask a good (exciting) question
before designing a clinical trial
Unmet medical needs
• In view of holistic medicine
• Complimentary to mainstream medicine
Unanswered questions
• Critical appraisal of current evidence
Answerable
• Practical methodology
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
9. Clinical Trials Design
Case series, Open exploratory study
Phase II Randomized controlled trial
• Dose range study is necessary
• Two stage design is a trend
• DBPC trial is preferred
Phase III Randomized controlled trial
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
10. Uncontrolled studies
Case series, Open study
Needs
1. Scientific records
2. Simple and well accepted endpoints
3. Clear documentation
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
15. Structure of Randomized Control
Trials
Treatment
Trial
subjects
Randomized
Endpoints
Control
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
16. Indications selection
Unmet needs
• Important diseases
• unsatisfactory efficacy or safety
• TCM better than western medicine
For examples:
•
•
•
•
Cancer
Cardiovascular disease
Degenerative diseases: OA, dementia…
Immunological diseases: allergy,
autoimmune disease…
• Functional diseases: neurosis, aging…
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
17. 選病
Trial subjects selection
Western
diagnosis
• May plus objective operable
Chinese syndrome (pattern)
• Diagnostic criteria
Inclusive
criteria
Exclusive criteria
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
18. 選方
Trial intervention
Traditional TCM formula
•
•
Licensed drug indication
Off-label use
New TCM drugs
•
•
•
魏正宗
New TCM formula
Crude extract of single herb or mixture
Pure compound
Functional foods
中山醫學大學附設醫院中藥臨床試驗中心
19. How to find a good TCM intervention
for clinical trial?
Literatures review
Modern research
Expert’s opinions
Pilot clinical trials
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
20. Structure of Randomized Control
Trials
Treatment
Trial
subjects
Randomized
Endpoints
Control
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
21. Methods of control
Placebo
control
• 目的在於克服對照組病人由於心理因素所造成
的偏倚 (bias)
• 常用無藥理作用的乳糖、澱粉等，安慰劑要求
在外觀、顔色、形狀與試驗藥物完全一致
• 要特別注意醫療道德上的可行性。
Standard control (active control)
• 研究藥物的療效時，可以公認的常規有效療法
作爲對照。
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
22. Add-on therapy design
Standard therapy as background for all
arms
Add-on TCM or placebo to see the
addictive effect
Ethic consideration
Better compliance
As complimentary therapies
魏正宗
中山醫學大學附設醫院中藥臨床試驗中心
29. CSMUH Chinese Medicine Clinical Trial Center
SMO (site-management organization)
model granted by the DOH, Taiwan
SMO (site-management organization)
SMO (site-management organization)
GCRC (General Clinical Research Center)
GCRC (General Clinical Research Center)
CMCTC Chinese Medicine Clinical Trial Center
CMCTC Chinese Medicine Clinical Trial Center
Administrative
Administrative
2 assistants
2 assistants
魏正宗
Clinical affairs
Clinical affairs
1 CRA/manager
1 CRA/manager
6 CRC
6 CRC
Data management
Data management
2 Statistician
2 Statistician
3 MD
3 MD
中山醫學大學附設醫院中藥臨床試驗中心
33. TCM Publications, 2011-2012
•Tsung‐Yuan Yang, James Cheng‐ Chung Wei, Ming‐Yung Lee, C. M. Balance Chen and
Kwo‐Chang Ueng. A randomized, double-blind, placebo-controlled study to evaluate the
efficacy and tolerability of Danshen (Salvia miltiorrhiza) as add-on anti-hypertensive
therapy in Taiwanese patients with uncontrolled hypertension. Phytotherapy Research
2011DOI: 10.1002/ptr.3548. (SCI, Impact factor: 2.469 ； Ranking: 32/59 ； 54%) Equal
contribution to first author.
•Chien-Ying Lee, Ming-Shiou Jan, Min-Chien Yu, Chun-Che Lin, James Cheng-Chung
Wei*, and Hung-Che Shih* Relationships between Adiponectin and Leptin and Blood
Lipids in Hyperlipidemia Patients Treated with Red Yeast Rice. Forschende
Komplementärmedizin (Research in Complimentary Medicine). 2012 accepted (Impact
Factor: 1.652, ranking 9/22). *Co-Correspondence
•Chien-Ying Lee, Min-Chien Yu, Chun-Che Lin, Ming-Yung Lee, James Cheng-Chung
Wei, Hung-Che Shih. Efficacy and Safety of Herbal Medicine Yun-Cai Tea in the
Treatment of Hyperlipidemia: A Double-Blind Placebo-controlled Clinical Trial. Chinese
Journal of Integrative Medicine 2012 published online (SCI) *Correspondence
Chung Shan Medical University Hospital
Chinese Medicine Clinical Trial Center
06
35. Contact us:
CSMUH Chinese Medicine Clinical Trial Center
http://www.csh.org.tw/into/herb
James Cheng-Chung Wei, MD, PhD ( 魏正宗 )
wei3228@gmail.com
Chung Shan Medical University Hospital
Chinese Medicine Clinical Trial Center
