- 1. Protocol design James Cheng-Chung Wei, MD,PhD.
2. Science
- Science is built up with facts, as a house is with stones. But
a collection of facts is no more a science than a heap of stones is
a house.
- Measurable, reproducible and comparable .
-
-
- Jules Henri Poincare : La Science et LHypothese ( 1908)
3. 4. Scale-up 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
Formulation Chemistry and Physical Characterization Phase III
Botanicals with historical documentation of safe human use 5. The
Evidence Pyramid 6. Starting from
- Ask a good (exciting) question!
7. Ask a good (exciting) question
-
- Ask your question in one sentence
-
- Review & critical appraisal of literatures
8. How to ask a goog question? ~Fromgooddaily patients care
- Delicate care of individual patient
9. Ask a good question
-
- I: Intervention (E:Exposure)
10. Before study design
11. Clinical Trials Design
- Early exploratory study (Pilot study)
- Phase II Randomized controlled trial (Proof-of-concept
study)
-
- Dose range study is necessary
- Phase III Randomized controlled trial (Confirmatory study)
12. Case series: Drug A in the treatment of URI
- Trial subjects: common cold
- Conclusion: Drug A is effective in the treatment of common
cold?
13. Cases series Drug A in the treatment of obesity
- Design: open study, one arm
- Conclusion: Drug A can reduce body weight?
14. Uncontrolled studies
15. Uncontrolled studies
-
- Objective and well accepted endpoints
16. Gold standard ~ randomized controlled trials 17. Structure
of Randomized Control Trials Randomized Endpoints Trial subjects
TreatmentControl 18. Trial subjects selection
19. TCM in the treatment of hyperuricemia Patients selection
- Inclusion criteria: serum uric acid level more than 8
mg/dl.
-
- recent gouty attack within 2 weeks
-
- serum creatinine more than 3 mg/dl
-
- change of background uric acid-lowering therapies including
allopurinol, benzbromarone, probeneci,sulfipyrazone, azathioprine,
aspirin (>325 mg), atorvastatin, fenofibrate, losartan,
thiazide, steroid, estrogen, oral contraceptive pills within 2
weeks.
20. How to find agood intervention for clinical trial?
21. Structure of Randomized Control Trials Randomized Endpoints
Trial subjects TreatmentControl 22. Methods of control
- Standard control (active control)
23. Bad controls
- Self control (before-and-after study)
24. Controlled trial: Drug A and B in the treatment of
obesity
- Sample size: 30 in each arm
- Intervention: Drug A or B
- 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?
25. Controlled trial: Drug A and B in the treatment of
obesity
- Sample size: 30 in each arm
- Intervention: Drug A or B
- 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?
26. Double blind +/- double dummy Randomization Endpoints Trial
subjects A "Placebo or B 27. Randomization
- ( Baseline comparability)
28. Randomization
29. Endpoints
- Scientific: well accepted, clear and operable outcome
measurements
- Survival> QOL>Symptomatic>Laboratory
- TCM endpoints if operable
- Primary and secondary endpoints
30. Blind Method
31. Crossover Clinical Trial Drug B Drug A W A S HO U T Phase 1
Period Eligible Patients /subjects Drug A Drug B Informed consent
Drug B Drug A Phase 2 32.
- (crossover design) (period) (wash-out period) (carryover
effect)
33. Adaptive designs
- Stopping trial early due to safety, futility, or efficacy
- Sample size re-estimation
34. Protocol
35. Research team & Resources
- Principal investigator (PI), Co-PI, Sub-PI
- Study nurse / Clinical research coordinator (CRC)
- Statistician / Epidemiologist
36. Chung Shan Medical University Hospital Chinese Medicine
Clinical Trial Center GCRC(General Clinical Research Center)
- SMO (site-management organization) model granted by the DOH,
Taiwan
SMO(site-management organization) GCRC(General Clinical Research
Center) CMCTCChinese Medicine Clinical Trial Center Administrative
2 assistants Clinical affairs 1 CRA/HN 4 CRC Data management 1
Statistic PhD 2 Statistic MS 2 MD1 Pharmacist 20 Consultants
37.
38. Contact us: CSMUH Chinese Medicine Clinical Trial Center
http://www.csh.org.tw/into/herb James Cheng-Chung Wei, MD, PhD (
)[email_address]