1. “So You Think You Know GCP …” Session S794 Jill Matzat, RN, BSN, CCRA, CCRT President, Medical Research Management & CRA Solutions, Inc. Paul Below, CCRA, CCRT Clinical Research Consultant, P. Below Consulting, Inc.

2. Disclosure Jill Matzat and Paul Below have no relevant financial relationships in relation to this educational activity

3. Background This presentation was developed to counter numerous misconceptions and myths about Good Clinical Practice overheard by the presenters during their careers This presentation is intended to teach GCP concepts using a quiz format (audience polling is available via text message voting)

4. Learning Objectives Define Good Clinical Practice (GCP) Differentiate between FDA requirements (stated in regulation) and FDA recommendations (stated in guidance documents) in several key areas Identify several circumstances where “industry best standard” practices exist that go above and beyond what the FDA requires and even recommends

5. What is Good Clinical Practice? Good Clinical Practice (GCP) is a unified standard for designing, conducting, recording, and reporting trials that involve human subjects GCP is composed of many parts that cannot be found in any one book or place

6. GCP Other Federal Regulations FDA Regulations (21 CFR) State Law Local Law (Institutional and IRB Policies) FDA Guidance Documents ICH Guidelines for GCP Sponsor SOPs Industry Best Practices

7. So You Think Know GCP … The following slides are a series of questions to test your knowledge of GCP You will be able to submit your answers via text messaging All answers are anonymous (no one is identified by name or phone number)

8. How To Vote via Texting Example Question: What is your favorite color? Blue(72612) Red(72613) Green(72614) Yellow(72615) To vote, text the corresponding keyword to 22333 NOTE: Standard text messaging rates apply.

9. Some Notes on Terminology “The FDA requires” = it is specified in regulation “The FDA recommends” = it is specified in an FDA guidance document

10. Informed Consent Question

11. FDA regulations require the following: AnswerKeyword The ICF must be signed by the subject239432 The ICF must be signed by the person obtaining consent 239433 The ICF must be signed by the investigator239434 Every page of the ICF must be initialed by the subject 239435 All of the above239436 Text your answer (keyword) to 22333

12. FDA regulations require the following: AnswerKeyword The ICF must be signed by the subject239432 The ICF must be signed by the person obtaining consent 239433 The ICF must be signed by the investigator239434 Every page of the ICF must be initialed by the subject 239435 All of the above239436 Per 21 CFR 50.27, the informed consent form should be “signed and dated by the subject or the subject's legally authorized representative at the time of consent” However, FDA guidance (ICH GCP) also recommends that the form be signed by the person obtaining the consent

13. Other ICF Misconceptions It is acceptable for the study staff to date the consent for the subject if they forgot to do so A spouse can always function as a “legally authorized representative” Consent forms must be written at a 6th grade reading level

14. Form FDA 1572 Question

15. FDA guidance recommends the following: AnswerKeyword The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial 236113 The 1572 must be updated when new sub- investigators are added to Box #6 236114 The Principal Investigator must be a physician 236115 Only one Principal Investigator should be listed in Box #1 236116 All of the above 236117 Text your answer (keyword) to 22333

16. FDA guidance recommends the following: AnswerKeyword The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial 236113 The 1572 must be updated when new sub- investigators are added to Box #6 236114 The Principal Investigator must be a physician 236115 Only one Principal Investigator should be listed in Box #1 236116 All of the above 236117 A recent FDA Guidance Document was issued in May 2010 to clarify the agency’s expectations regarding completion the form.

17. Other 1572 Misconceptions Must be completed on a double-sided form Must be typed Study Coordinators should not be listed as Sub- Investigators in Box #6 All rotating study staff (e.g., residents, fellows) must be listed as Sub-Investigators in Box #6

18. Curriculum Vitae (CV) Question

19. FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) 239968 CVs must be collected at the beginning of the study 239969 CVs must be “up-to-date”239970 CVs must be signed and dated by the completer 239971 All of the above 239972 Text your answer (keyword) to 22333

20. FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) 239968 CVs must be collected at the beginning of the study 239969 CVs must be “up-to-date”239970 CVs must be signed and dated by the completer 239971 All of the above 239972 Per 21 CFR 312.23 (a)(6)(iii)(a), Sponsors need to include in their initial IND submission a statement of the qualifications (curriculum vitae or other statement of qualifications) of each Principal Investigator and only the names of each Sub-Investigator

21. FDA regulations require the following: AnswerKeyword CVs must be collected for all investigators (PI and all Sub-investigators) 239968 CVs must be collected at the beginning of the study 239969 CVs must be “up-to-date”239970 CVs must be signed and dated by the completer 239971 All of the above 239972 However, FDA guidance (ICH GCP) recommends that the Investigator CV be “up-to-date” (4.1.1) and be collected for all PIs and Sub-Investigators (8.2.10)

22. Case Report Form Question

23. FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry 241939 When CRFs are used as source documents, they should be specified in the protocol 241940 Sponsors may make changes to the CRF data with the authorization of the investigator 241941 All of the above 241942 None of the above 241943 Text your answer (keyword) to 22333

24. FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry 241939 When CRFs are used as source documents, they should be specified in the protocol 241940 Sponsors may make changes to the CRF data with the authorization of the investigator 241941 All of the above 241942 None of the above 241943 All of the above are specified in ICH GCP

25. FDA guidance recommends the following: AnswerKeyword CRF corrections should be dated and initialed and should not obscure the original entry 241939 When CRFs are used as source documents, they should be specified in the protocol 241940 Sponsors may make changes to the CRF data with the authorization of the investigator 241941 All of the above 241942 None of the above 241943 There is nothing in FDA regulation or guidance that specifies that CRF corrections must be made with a single line through the original entry

26. Investigational Product Question

27. FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access 239961 IP must be environmentally monitored and controlled 239962 IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” 239963 All unused IP must be returned to the sponsor at the end of the trial 239964 Text your answer (keyword) to 22333

28. FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access 239961 IP must be environmentally monitored and controlled 239962 IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” 239963 All unused IP must be returned to the sponsor at the end of the trial 239964 Labeling requirements are specified for drugs in 21 CFR 312.6 and for devices in 21 CFR 812.5

29. FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access 239961 IP must be environmentally monitored and controlled 239962 IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” 239963 All unused IP must be returned to the sponsor at the end of the trial 239964 The only language in the device or drug regulations related to IP storage concerns investigational drugs that are controlled substances (21 CFR 312.69, “storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited …”)

30. FDA regulations require the following: AnswerKeyword Investigational product (IP) must be stored in a secure location with limited access 239961 IP must be environmentally monitored and controlled 239962 IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.” 239963 All unused IP must be returned to the sponsor at the end of the trial 239964 21 CFR 312.59 indicates sponsors “may authorize alternative disposition” for unused investigational drugs 21 CFR 812.110 indicates that investigators can “otherwise dispose of the device as the sponsor directs”

31. Emergency Use of IP Question

32. If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB? AnswerKeyword Promptly 241377 Within 24 hours 241378 Within 3 calendar days 241379 Within 3 working days 241380 Within 5 working days 241381 Text your answer (keyword) to 22333

33. If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB? AnswerKeyword Promptly 241377 Within 24 hours 241378 Within 3 calendar days 241379 Within 3 working days 241380 Within 5 working days 241381 Reporting requirements for all products are specified in 21 CFR 50.23: “shall be submitted to the IRB within 5 working days after the use of the test article”

34. Regulatory Document Question

35. FDA regulations require that the following documents be signed by the investigator: AnswerKeyword Trial Delegation Log241496 Completed and final case report forms241497 Financial disclosure forms241498 Protocol signature pages241499 All of the above241500 None of the above241501 Text your answer (keyword) to 22333

36. FDA regulations require that the following documents be signed by the investigator: AnswerKeyword Trial Delegation Log241496 Completed and final case report forms241497 Financial disclosure forms241498 Protocol signature pages241499 All of the above241500 None of the above241501 The only document specified by FDA regulation that must be signed by the investigator is the Form FDA 1572 (for drugs) or the Investigator Agreement (for devices)

37. Closing Thoughts Most FDA requirements are vague and open to some interpretation Most of what we do in clinical research is driven by our own industry best practices and not FDA requirements or even recommendations Be careful when telling an investigator site, “You have to do this because the FDA requires it” unless you are certain that it is specified by regulation

38. Poll Results Complete poll results are available at: www.pbelow-consulting.com/ACRP2011.html www.pbelow-consulting.com/ACRP2011.html

39. Your Chance to Ask Us Questions

40. Contact Information Jill Matzat jmatzat@cra-training.com jmatzat@cra-training.com Come visit Jill at the Medical Research Management booth in the exhibit hall Paul Below paul@pbelow-consulting.com paul@pbelow-consulting.com Paul presents again on Monday at 4:15 pm (S831 - You've Discovered Fraud - Now What Do You Do?) Poll results available at www.pbelow-consutling.com/ACRP2011.html