1. VHA Handbook 1200.05 K. Lynn Cates, M.D. Assistant Chief Research & Development Officer Director, PRIDE HRPP 201 March 24, 2011

2. VHA Handbook 1200.05 VHA Office of Research & Development (ORD) ORD is responsible for 1200.05 content Interpreting 1200.05 Answering questions about 1200.05 Email address for unencrypted questions VHACO120005Q@va.gov VHACO120005Q@va.gov 2

3. 3 VHA Handbook 1200.05 Overview Clarify new requirements Point out issues that have created confusion in the past Ensure 1200.05 is interpreted consistently

4. Does the IRB Need to Re-Review Existing Research? Not unless required by local standard operating procedures (SOPs) Subsequent requirements are published by ORD 4

5. 5 VA Facility Director Responsibilities Advertising The facility Director is responsible for ensuring that recruiting documents, flyers, and advertisements for non- VA research are not posted within or on the premises of a VA facility (VHA Handbook 1200.05, Paragraph 5n) General guidance may be posted Veterans may speak with their health care providers Information on clinical trials is at : http://clinicaltrials.govhttp://clinicaltrials.gov

6. 6 VA Facility Director Responsibilities Advertising A clinician May tell a patient about a non-VA study May give a patient contact information for a non-VA study May not recruit patients for a non-VA study May not obtain informed consent for a non-VA study May not put recruitment flyers out for a non-VA study ? Get the patient’s consent to give the patient’s name and contact information to the non-VA investigator Must abide by all VA privacy, confidentiality, and information security requirements Document getting the patient’s permission in writing

7. Investigator Responsibilities Paragraph 9 Overseeing the research team Obtaining all relevant approvals in writing before starting the study (see VHA Handbook 1200.01) Implementing the protocol as approved by the IRB Documenting how the protocol is being implemented 7

8. Investigator Responsibilities Paragraph 9 Informed Consent Must use the most recent IRB-approved version of Informed Consent Form (10-1086) Must use VA-specific provisions (e.g., research- related injury) Ensure consistency among Informed Consent Form Protocol HIPAA authorization 8

9. Research Protocol Paragraph 10 Differentiate usual care from research activity Provide privacy and confidentiality section Provide information security plan Provide for reuse of data 9

10. IRB Composition Paragraph 12 Individuals who cannot serve as IRB members (voting or nonvoting) Facility Director & Director’s administrative staff Chief of Staff Other local leadership (e.g., Quadrad members, Chief Nurse Executive) Research Compliance Officers Nonprofit directors or staff 10

11. IRB Composition Paragraph 12 – Ex Officio, Nonvoting Members Individuals who may serve as ex officio, nonvoting* IRB members VA facility research office staff ACOS for R&D AO for R&D IRB administrative staff Affiliate (not VA) IRB administrative staff may be voting members of the affiliate IRB Privacy Officer Information Security Officer *In 1200.05, “ex officio” = “nonvoting” 11

12. IRB Composition Paragraph 12 – Alternate IRB Members What are the criteria for selecting alternate IRB members? Expertise of the member Member’s contributions relative to the IRB’s portfolio Broad portfolio – one MD could fill in for another Cardiology – a cardiologist must fill in for a cardiologist If the IRB membership does not have expertise for a given study, it has an obligation to seek expert consultation 12

13. Review and Approval of Research Paragraph 15 IRB considerations for each project* 1. Is the project research? 2. If yes, does the research involve human subjects? 3. If yes, the IRB must determine if the human research project is exempt from IRB review *The considerations should be addressed in this order 13

14. Continuing Review Paragraph 22 Continuing review must occur not less than once per year The IRB may review within 30 days prior to expiration and still retain anniversary date 14

15. Continuing Review Expiration of IRB Approval, Paragraph 22g No grace period to extend conduct of research beyond the expiration date If approval expires Stop all research activities Immediately submit to IRB Chair a list of subjects who could be harmed by stopping study procedures 15

16. IRB Approval Date Paragraph 24 The date of IRB approval of a study is used to determine when continuing review must be performed Convened IRB review and approval Convened IRB review and approval with minor conditions* Convened IRB review with substantive conditions Expedited review *The approval date of the informed consent form may be later than that of the protocol if it was approved contingent on minor modifications to the informed consent form 16

17. General Requirements for Informed Consent, Paragraph 30 If someone other than the investigator conducts the consent process, the investigator must prospectively designate in writing in the protocol or application to the IRB, the individual who will have this responsibility 17

18. Additional Elements of Informed Consent Subparagraph 32b VA-specific requirements include (if relevant) Future use of specimens or data Re-contacting subjects for future studies Disclosure of study results 18

19. Documentation Informed Consent Paragraph 33 VA Form 10-1086 must be used for all VA approved research Except DoD studies with active duty military personnel when no VA-specific language is necessary (Paragraph 33a) Must use the most recent IRB-approved version of informed consent form (i.e., the date the informed consent form was sent to the IRB for approval)* *The date on the IRB-approval stamp can never be earlier than the “version” date or the protocol IRB approval date 19

20. Documentation Informed Consent Paragraph 33 - Signatures Signature blocks are required for the subject and the person obtaining the consent Signature and Date A witness is not required to sign an informed consent form u nless The IRB requires a witness signature A short form is employed* * A witness is always required for a short form 20

21. Documentation Informed Consent Paragraph 33 – Witness Signature How can the investigator remove the block for a witness signature from the informed consent form of an ongoing study? The local facility’s SOPs must allow for informed consent forms that do not have witness signatures The investigator must submit an amendment to the IRB The IRB must approve the amendment (but the IRB has the prerogative to disapprove) 21

22. Documentation Informed Consent Paragraph 33 – Witness Signature The investigator cannot Leave the witness signature block blank Strike-out the witness signature block Put N/A (not applicable) in the witness signature block 22

23. Informed Consent Alternative Procedures What is required for documentation of the basic element of informed consent “A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject” (38 CFR 116.(a)(4)) if there are no alternative procedures or courses of treatment? None, unless required by the IRB. The IRB does not need to find or document, & the informed consent form/process does not need to include language saying there are no alternatives 23

24. Informed Consent IRB Documentation What is required for IRB documentation of its approval of an informed consent procedure that does not include, or alters, some or all elements of informed consent? The IRB can say “all criteria have been met” However, it is much better for the IRB to document protocol-specific reasons why each of the criteria has been met (if this information is not in the IRB minutes, information supporting the IRB determination must be in the IRB protocol file) 24

25. HIPAA Authorization Paragraph 37 HIPAA Authorization must be a standalone document For ongoing studies with the informed consent form & HIPAA authorization combined, do they need to be split into two documents (e.g., at the time of continuing review)? Not unless your IRB determines they should be separated 25

26. Investigational Drugs & Devices Paragraphs 39 & 40 Investigators and IRBs must follow both FDA regulations and VA requirements 26

27. 27 Engaged in Human Subjects Research Paragraph 50 Generally, VA facility is “engaged”* when that VA facility’s employee obtains the following for research purposes Data about the subjects through intervention or interaction Identifiable private information about the subjects; or Informed consent from the subjects for the research *See OHRP Guidance October 16, 2008

28. 28 Not Engaged in Human Subjects Research Paragraph 51 If a VA Facility is not “engaged” in research, it Has no jurisdiction over the study Does not have to have an FWA Does not have to get its IRB or Research & Development Committee approval However, its Facility Director may determine that study cannot be conducted there

29. Engagement Multi-Site Studies Who decides whether or not a local site is engaged? The PI’s IRB of record Does the PI need to obtain approval from sites that are not engaged? No, but The PI must notify the Director of the site that is not engaged The Director has the authority to disapprove 29

30. 30 Engagement Dual Appointment Investigators How can you determine if the VA is “engaged”? Is engaged if she uses VA resources (e.g., works on her VA time, uses VA space or equipment) Is not engaged if she does not use VA resources (e.g., works on her university time, in her university office & lab, using her university computer & university research team)

31. Voice, Video, or Photographs for Research Purposes, Paragraph 55 Informed Consent (VA Form 10-1086) Consent for Use of Picture and/or Voice (VA Form 10- 3203) only needed when subject is a patient 31

32. Accreditation Paragraph 64 VA facilities with Federalwide Assurances (FWAs) must achieve and maintain Full Accreditation of their Human Research Protection Programs (HRPPs) New IRB arrangements Affiliate responsibilities Obtain Full or Qualified Accreditation, or Cooperate with the VA’s accreditation application process VA facility responsibilities when affiliate is not on target to obtain accreditation Maintaining HRPP accreditation 32

33. Questions About New VHA Handbook 1200.05 Preferred - Send unencrypted questions via e-mail to VHACO120005Q@va.govVHACO120005Q@va.gov If urgent and/or encrypted, please contact: Kevin Nellis Kevin.Nellis@va.govKevin.Nellis@va.gov Lynn Cates Lynn.Cates@va.govLynn.Cates@va.gov 33

34. 34