Upload
netnk
View
153
Download
4
Embed Size (px)
DESCRIPTION
Citation preview
2. Protocol
3. Science
4. 5. 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 6. The Evidence Pyramid 7. Starting from
8. Ask a good (exciting) question
9. How to ask a goog question? ~Fromgooddaily patients care
10. Ask a good question
11. Before study design
12. Clinical Trials Design
13. Cases series Drug A in the treatment of obesity
14. Uncontrolled studies
15. 16. Gold standard ~ randomized controlled trials 17. Structure of Randomized Control Trials Parallel, two arms design Randomized Endpoints Trial subjects TreatmentControl 18. Trial subjects selection
19. How to find agood intervention for clinical trial?
20. Intervention (treatment)
21. Methods of control
22. Bad controls
23. Controlled trial: Drug A and B in the treatment of obesity
24. Double blind +/- double dummy Randomization Endpoints Trial subjects A "Placebo or B 25. Blind Method
26. Randomization
27. Randomization
28. Block Randomization
29. Endpoints
30. (primary endpoint)
31. Dose ranging study anti-dsDNA Ab 10 IU/ml Meet allcriteria Randomization (~ 588 patients) 20% 40% 40% ~ 196 patients ~ 392 patients
32. ATTAIN study abatacept in inadequate responders to TNF-targeted therapy Day 1 12 months 24 months Randomization Placebo + DMARD (n=133) Fixed-dose abatacept~10 mg/kg + DMARD (n=258) Randomization=2:1 Anti-TNF inadequate responders with active disease (n=393)* Co-primary endpoints: ACR 20 and Physical Function Fixed-dose abatacept~10 mg/kg + DMARD (n=317) Double-blindOpen-label phase 6 months Open label phase ongoing *DMARDs continued, antiTNF washout period (2860 days); Based on patient weight range; Patients randomized to the placebo group in the first 6 months switched to abatacept during OL period; LTE=long-term extension Genovese M, et al. N Engl J Med 2005;353:11141123 33.
Biologics + NSAID + Sulfasalazine Biologics - NSAID - Sulfasalazine Factorial design 2 5 11 Biologics + NSAID - Sulfasalazine Biologics - NSAID + Sulfasalazine
23 34. 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 35.
36. Phase II/III design 37. Double blind double dummy design Non-inferiority vs superiority design Abatacept SC (weekly) Placebo IV (monthly) +IV loading dose Abatacept IV (monthly) Placebo SC (weekly) Abatacept SC (weekly) 15 Day 169 Commercial Availability 720 subjects 720 subjects Long-Term Extension ongoing Short Term 6 months 113 1 43 29 57 85 Days 141 Monthly Phone Visits +Quarterly Office Visits All subjects 38. Adaptive designs
39. Study flow chart 40. Statistics &Sample size estimation
41. Sample size estimation web http://stat.ubc.ca/~rollin/stats/ssize/
http://www.csh.org.tw/into/herb 42. Comparing Proportions for Two Independent Samples 43. Comparing Means for Two Independent Samples http://stat.ubc.ca/~rollin/stats/ssize/ 44. TCM in Patients with Hyperuricemia. A DBPC clinical trial
45. Ultracet in Ankylosing Spondylitis. A DBPC clinical trial.
46. Data Management Process CRF CRF CRA CDM CRF Data lock Data entry Data entry: Data validation Data analysis 47. Case Report Form
48.
49. Research team & Resources
50. Chung Shan Medical University Hospital Chinese Medicine Clinical Trial Center GCRC(General Clinical Research Center)
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 51.
52. Contact us: CSMUH Chinese Medicine Clinical Trial Center http://www.csh.org.tw/into/herb James Cheng-Chung Wei, MD, PhD ( )[email_address]