2. ScienceScience
Science is built up with facts, as a houseScience is built up with facts, as a house
is with stones. But a collection of facts isis with stones. But a collection of facts is
no more a science than a heap of stonesno more a science than a heap of stones
is a house.is a house.
Measurable, reproducible andMeasurable, reproducible and
comparablecomparable..
Jules Henri Poincare : La Science et LJules Henri Poincare : La Science et L’’Hypothese ( 1908)Hypothese ( 1908)
4. 新藥開發流程
Scale-up
臨床前研究 臨床試驗 新藥審核
12-24 months
1-4
month
9-12
months 12-24 months
6-18 months
Phase II
Phase IV
Pharmacology and Pharmacokinetics
Animal Safety Testing
Submit
IND
Submit NDA NDA Approval
FormulationChemistry and Physical Characterization
Phase III
新藥監視
Botanicals with historical
documentation of safe human use
7. 中山醫學大學附設醫院
Ask a good (exciting) question
Clinical relevant
• Unmet medical needs
Clear
• Ask your question in one sentence
• Don’t be too ambitious
Innovative
• Unanswered questions
• Review & critical appraisal of literatures
Answerable
• Practical methodology
8. 中山醫學大學附設醫院
Ask a good question
問題之結構 (PICOT)
• P: Participant
• I: Intervention (E:Exposure)
• C: Comparison
• O: Outcome
• T: Time
10. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Clinical Trials Design
Case series
Early exploratory study (Pilot study)
Phase II Randomized controlled trial
(Proof-of-concept study)
• Dose range study is necessary
• DBPC trial is preferred
Phase III Randomized controlled trial
(Confirmatory study)
11. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Case series:
Drug A in the treatment of URI
Sample size: 30
Trial subjects: common cold
Intervention: Drug “A”
Duration: 14 days
Endpoint: symptoms
Result: 90% cured.
Conclusion: Drug A is effective in the
treatment of common cold?
12. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Cases series
Drug A in the treatment of obesity
Sample size: 30
Trial subjects: obesity
Intervention: Drug “A”
Design: open study, one arm
Duration: 30 days
Endpoint: body weight
Result: 100 kg to 90 kg.
Conclusion: Drug A can reduce body
weight?
18. TCM in the treatment of hyperuricemiaTCM in the treatment of hyperuricemia
Patients selectionPatients selection
Inclusion criteria: serum uric acid level moreInclusion criteria: serum uric acid level more
than 8 mg/dl.than 8 mg/dl.
Exclusion criteriaExclusion criteria
recent gouty attack within 2 weeksrecent gouty attack within 2 weeks
serum creatinine more than 3 mg/dlserum creatinine more than 3 mg/dl
AST more than 100 IUAST more than 100 IU
change of background uric acid-lowering therapieschange of background uric acid-lowering therapies
including allopurinol, benzbromarone, probeneci,including allopurinol, benzbromarone, probeneci,
sulfipyrazone, azathioprine, aspirin (>325 mg),sulfipyrazone, azathioprine, aspirin (>325 mg),
atorvastatin, fenofibrate, losartan, thiazide, steroid,atorvastatin, fenofibrate, losartan, thiazide, steroid,
estrogen, oral contraceptive pills within 2 weeks.estrogen, oral contraceptive pills within 2 weeks.
19. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
How to find a good intervention
for clinical trial?
Literatures review
Modern research
Expert’s opinions
Pilot clinical trials
21. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
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。
22. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
“Bad” controls
Self control (before-and-after study)
• 如用藥前後的自身對比觀察；
• 對照與實驗在同一物件身上進行，例如身體對稱部位
的比較觀察
Historical control
• 已先前研究之結果為對照
• 只適用於”不隨時空環境不同而改變結果”之疾病
Blank control
• 在對照組不加任何處理的“空白”條件下進行觀察。
23. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Controlled trial:
Drug A and B in the treatment of obesity
Sample size: 30 in each arm
Trial subjects: obesity
Intervention: Drug “A” or “B”
Duration: 14 days
Endpoint: body weight
Result: in arm A: 100 kg to 50kg, in arm B: 80
kg to 40 kg.
Conclusion: Drug A is better than B in
reducing body weight?
24. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Controlled trial:
Drug A and B in the treatment of obesity
Sample size: 30 in each arm
Trial subjects: obesity
Intervention: Drug “A” or “B”
Duration: 90 days
Endpoint: body weight
Result: in arm A: 100 kg to 80kg, in arm B: 80
kg to 70 kg.
Conclusion: Drug A is better than B in
reducing body weight?
30. 31
Crossover Clinical Trial
Drug B
Drug A
W
A
S
H
O
U
T
Phase 1
Period
Eligible
Patients /
subjects
Drug A
Drug B
Informed
consent
Drug B
Drug A
Phase 2
34. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Research team & Resources
1. Principal investigator (PI), Co-PI, Sub-PI
2. Study nurse / Clinical research
coordinator (CRC)
3. Statistician / Epidemiologist
35. 魏正宗 中山醫學大學附設醫院中藥臨床試驗中心
Chung Shan Medical University Hospital
Chinese Medicine Clinical Trial CenterChinese Medicine Clinical Trial Center
GCRCGCRC (General Clinical Research Center)(General Clinical Research Center)
SMO (site-management organization)
model granted by the DOH, Taiwan
SMO (site-management organization)
GCRC (General Clinical Research Center)
CMCTC Chinese Medicine Clinical Trial Center
SMO (site-management organization)
GCRC (General Clinical Research Center)
CMCTC Chinese Medicine Clinical Trial Center
Administrative
2 assistants
Administrative
2 assistants
Clinical affairs
1 CRA/HN
4 CRC
Clinical affairs
1 CRA/HN
4 CRC
Data management
1 Statistic PhD
2 Statistic MS
Data management
1 Statistic PhD
2 Statistic MS
2 MD
1 Pharmacist
20 Consultants
2 MD
1 Pharmacist
20 Consultants
37. Chung Shan Medical University Hospital Chinese Medicine Clinical Trial Center
Contact us: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
