This document summarizes a conference on Good Clinical Practice (GCP) compliance. It discusses the objectives of clinical research and challenges to harmonizing GCP standards internationally. It also outlines current ethical challenges in clinical trials and dimensions of GCP frameworks. The document proposes that further developing national and regional GCP guidance, broadening the scope of GCP, and establishing appropriate platforms can help advance GCP. It provides guidance on investigator responsibilities and comments on adverse event reporting.

1. Highlights from ExLPharma’s Proactive GCP ComplianceMarch 29-31, 2010Arlington, VA

2. GCP in Emerging RegionsEthics, Quality, and Compliance1

3. The Objectives of Clinical ResearchTo Contribute to Public HealthTo Contribute to Health ScienceTo Contribute to Economic Development

4. Good Clinical PracticeA Set of Responsibilities‘a process that makes all parties to a study responsible for patient safety and study quality’

5. US & EU Objectives inHarmonizing GCP(3 August 2009, Launch of a Bilateral GCP Initiative)To achieve common understandings and practicesTo share standards and methodologiesTo share knowledgeTo share resourcesTo improve human subjects protections

6. Challenges to GCP HarmonizationThe extensive reach of clinical trialsThe complexity of law and regulationLack of an internationally agreed code of ethics for human research protectionsThe progress of medical scienceThe lack of appropriately representative platforms

7. Current Ethical Challenges to GCP in Clinical Trials (1)The use of control arms (placebo)‘Standard of care’Informed consent processCommunity consultationIndividual and community access to researchThe role & responsibility of ethics committees (IRBs/ECs)Compensation for trial injuryPatient/Participant Confidentiality and PrivacyLocating phase I, II, and III trialsPharmacovigilance

8. Current Ethical Challenges to GCP in Clinical Trials (2)Medical treatment during the course of researchProduct availabilitySponsorshipLiability & InsuranceTissuesStem Cell ResearchData ProtectionMonitoring (DMCs)Data OwnershipProprietary Information/KnowledgePublishing Clinical Trial Information and ResultsBotanical/Traditional Medicines

9. Dimensions of GCPGeneral FrameworksWHO GCPICH GCPRegional/Applied FrameworksEU GCPUS CFRNational/Applied GCP GuidelinesChina, India, Russia, Singapore, Malaysia, Indonesia, South Korea Argentina, Brazil, Mexico, South America, South Africa, Turkey

10. The Way Forward for GCPFurther National & Regional Development(e.g., CTTI, The AfroGuide Project)A Broader Scope to Include All Health ResearchModernizing Guidance to Meet New Developments (e.g., Registries, Results Publication, DMCs, Insurance, Regulatory Science)Appropriate National, Regional, & International PlatformsA Broad and Comprehensive Vision Complimented by Small Steps

11. Proactive GCP ComplianceInvestigator Responsibilities Guidance& A Few Comments on AE Reporting

12. CI Responsibilities GuidanceSupervision of the Conduct of a Clinical InvestigationWhat Is Appropriate Delegation of Study-Related Tasks? What Is Adequate Training? What Is Adequate Supervision of the Conduct of an Ongoing Clinical Trial?What Are an Investigator’s Responsibilities for Oversight of Other Parties Involved in the Conduct of a Clinical Trial? Protecting the Rights, Safety, and Welfare of Study Subjects

13. Investigator Longevity(Length of time in active 1572)Source: CenterWatch Analysis 2001

14. Migration of Clinical Trials into the Private Sector

15. Standard Operating ProceduresSite Solutions Summit 2009 Survey

16. Quality Assurance ProgramSite Solutions Summit 2009 Survey

17. Tougher Protocols Harming PerformanceUS-based Pivotal Trial Protocols Executed1999-2002(Lower Complexity)2003-2006(Higher Complexity)Rising number of amendments

18. Number of CRF pages increases from 55 to 180 pages

19. Controlling for treatment duration, cycle times increased substantially

20. 12% longer protocol readiness to FPFV

21. 70% longer from protocol readiness to data lock

22. Enrollment rates worsened

23. Screen to randomized dropped from 75% to 59%

24. Randomized to study completion dropped from 69% to 48%Who Investigators Believe is Responsible for Compliance FailuresCenterWatch 2002 – FDA Analysis of Notices of Initiation of DisqualificationProceedings Letter

25. FDA Assessing InvestigatorsWhether delegated individuals were qualified to perform such tasks

26. Whether study staff received adequate training on how to conduct the delegated tasks and were provided with an adequate understanding of the study

27. Whether there was adequate supervision and involvement in the ongoing conduct of the studyDemonstrate Compliance With Appropriate DelegationDelegation of Responsibility Log

28. IRB questioning the acceptability of a persons credentials

29. Sponsors looking more seriously at who will do what, during the pre site visit

30. Investigator signing off on I/E source document But it’s more then a list, it’s knowing who CAN do what and who SHOULD do what

31. Demonstrate Compliance With TrainingReview training records during the pre site visit

32. Training files – GCP & study specific

33. Which brings up - How many times must one complete GCP training?

34. Training tab in each regulatory binder

35. Template to document such trainingDemonstrate Compliance With Supervision Evidence of study staff meetings

36. Evidence of meetings with sponsor monitor

37. Monitor letter – reviewed, signed and preferably responded to

38. PI & CRA meeting minutes*

39. Set of SOPs to Guidance requirements & GCPs

40. Evidence of Investigator involvement in the study

41. Appropriate signature on lab results

42. Signature on I/E source documentation worksheet

43. AE assessment (causality & severity)*Protecting the Rights, Safety and Welfare of Study SubjectsReview treatment of, and follow-up of SAEs/AEs (sponsor's protocol/policy)

44. Evidence of subject's Primary Care Physician having been informed (with subject's consent)