Clinical research = Daily medical practice

1. Session 21Practical interpretation of regulatory requirements fordocumenting the clinical trial for CRAs and CRCs creating the “squeaky clean” fileRuth Ann Nylen, PhD

2. Clinical research=Daily medical practice

4. Clinical trial documents required for studies to be submitted to regulatory authorities for registration of pharmaceutical products. Focus of Discussion

5. Key # 1 Establish study files before the study starts. Keys to the Clean Study File

6. IND-level Files • Protocol Level Files • Investigator Level Files • Correspondence with Regulatory Agencies Recommended File Set-up for Sponsors Sponsor

7. Confidential Documents • Study Conduct and Supplies • Regulatory Document • Subject Documents Recommended File Set-up for Investigative Sites Investigator

8. Key # 2 Generate and maintain an inventory list of all documents for each study. Keys to the Clean Study File

9. Key # 3 Document an activity when it occurs in the study. Keys to the Clean Study File

10. Key # 4 Review or proof read all documents for accuracy at the time each is prepared. Keys to the Clean Study File

11. Key # 5 Inventory documents regularly throughout a study. Keys to the Clean Study File

12. Key # 6 Address and resolve document problems immediately. Keys to the Clean Study File

13. Key # 7 Inventory and archive all study documents at study end. Keys to the Clean Study File

14. The ICH (International Conference on Harmonization) Good Clinical Practice Guideline, Part 8: • “Essential Documents for the Conduct of a Clinical Trial” • Published in the Federal Register May 9, 1997 • Available at www.ich.org The Best List of Study Documents

15. 8.2.1 Investigator’s Brochure Investigator Sponsor

16. 8.2.2 Signed protocol and amendments, andsample case report form Investigator Sponsor

17. 8.2.3 Information given to trial subject –Informed consent form –Any other written information–Advertisements (not in sponsor) Investigator Sponsor

18. 8.2.4 Financial aspects of the trial Investigator Sponsor

19. 8.2.5 Insurance statement(where required) Investigator Sponsor

20. 8.2.6 Signed agreement between involved parties, e.g., –Investigator/Institution and sponsor –Investigator/institution and CRO (sponsor is only where required)–Sponsor and CRO –Investigator/institution and authority(ies) (Where required) Investigator Sponsor

21. 8.2.7 Dated, documented approval/favorable opinion of IRB/IEC of the following:–Protocol and any amendments–CRF (if applicable)–Informed consent form(s)–Any other written information to be provided to the subject(s)–Advertisement for subject recruitment (if used)–Subject compensation (if any)–Any other documents given approval/favorable opinion Investigator Sponsor

22. 8.2.8 Institutional review board/independent ethics committee composition Where required Investigator Sponsor

23. 8.2.9 Regulatory authority(ies) authorization/approval/notification of protocol Where required Investigator Sponsor

24. 8.2.10 Curriculum vitae and/or other relevant documents evidencing qualifications of investigator(s) and sub-investigators Investigator Sponsor

25. 8.2.11 Normal value(s)/range(s) for medical/laboratory/technical procedure(s) and/or test(s) Investigator Sponsor

26. 8.2.12 Medical/laboratory/ technical procedures/tests–Certification or –Accreditation or –Established quality control and/or external quality assessment or–Other validation Where required Investigator Sponsor

27. 8.2.13 Sample of label(s) attached to investigational product container(s) Investigator Sponsor

28. 8.2.14 Instructions for handing of investigational product(s) and trial-related materials (if not included in protocol or Investigator’s Brochure) Investigator Sponsor

29. 8.2.15 Shipping records for investigational product(s) and trial-related materials Investigator Sponsor

30. 8.2.16 Certificate(s) of analysis of investigational product(s) shipped Sponsor

31. 8.2.17 Decoding procedures for blinded trials Investigator Sponsor

32. 8.2.18 Master randomization list Sponsor

33. 8.2.19 Pretrial monitoring report Sponsor

34. 8.2.20 Trial initiation monitoring report Investigator Sponsor

35. 8.3.1 Investigator’s Brochure updates Investigator Sponsor

36. 8.3.2 Any revisions to: –Protocol/amendment(s) and CRF–Informed consent form–Any other written information provided to subjects–Advertisement for subject recruitment (if used) Investigator Sponsor

37. 8.3.3 Dated, documented approval/favorable opinion of (IRB)/(IEC) of the following:–Protocol amendment(s)–Revision(s) of: Informed consent form Written information to be provided to the subject Advertisement for subject recruitment (if used) –Any other documents given approval/favorable opinion–Continuing review of trial Investigator Sponsor

38. 8.3.4 Regulatory authority(ies) authorizations/approvals or notifications where required for:Protocol amendment(s) and other documents Investigator Sponsor

39. 8.3.5 Curriculum vitae for new investigator(s) and/or subinvestigators Investigator Sponsor

40. 8.3.6 Updates to normal value(s)/range(s) for medical laboratory/technical procedure(s)/test(s) included in the protocol Investigator Sponsor

41. 8.3.7 Updates of medical/laboratory/technical procedures or tests–Certification or accreditation or established quality control and/or external quality assessment or–Other validation (where required) Where required Investigator Sponsor

42. 8.3.8 Documentation of investigational product(s) and trial-related materials shipment Investigator Sponsor

43. 8.3.9 Certificate(s) of analysis for new batches of investigational products Sponsor

44. 8.3.10 Monitoring visit reports Sponsor

45. 8.3.11 Relevant communications other than site visits –Letters –Meeting notes–Notes of telephone calls Investigator Sponsor

46. 8.3.12 Signed informed consent forms Investigator

47. 8.3.13 Source documents Investigator

48. 8.3.14 Signed, dated, and completed case report forms (CRFs) Original Copy Investigator Sponsor

49. 8.3.15 Documentation of CRF corrections Original Copy Investigator Sponsor

50. 8.3.16 Notification by originating investigator to sponsor of serious adverse events and related reports Investigator Sponsor