Exempt Research (Part 1): Categories 1-4

1. Dial in: (631) 992-3221 Access Code: 546-061-659 Slides in “Handout” Tab Exempt Research (Part 1): Categories 1-4 Soundia Duche, MA, MS Chief, Education and Training ORPP&E (formerly PRIDE) March 14, 2019

2. Overview Dial in: (631) 992-3221 Access Code: 546-061-659 Slides in “Handout” Tab • Background on Exempt Research • What Does Exempt from the Common Rule Mean? • Who Determines if a Study is Exempt? • When Would a Study Qualify for Exemption? • Who Oversees Exempt Research at the VA? • VA-specific Requirements for Exempt Research • Discussion of Exempt Categories 1-4 of the 2018 Rule with Case Studies • Open Q&A Session

3. What Does Exempt from the Common Rule Mean? Generally means not subject to the requirements of the Common Rule, but it is important to note that “exempt” does not mean exempt from all of the requirements of the Common Rule for some of the categories of human subject studies determined to be exempt under the 2018 Requirements.

4. Exempt Research is not Exempt from the Privacy Rule and the Privacy Act • The Privacy Rule (Health Insurance Portability and Accountability Act of 1996 - HIPAA) describes when written authorization is required before the use or disclosure of health care information that is not for a “permissible purpose” (i.e., treatment, payment, or healthcare operations) and specifies exceptions allowed by the regulations. • Protected Health Information (PHI) is defined as Individually-identifiable health information transmitted or maintained in any form or medium by a covered entity (VHA Directive 1605.01 para 3vv) • The presence of one or more of the 18 HIPAA identifiers* results in a dataset being considered “individually identifiable” • Studies involving access to protected health information require either Privacy Board approval of a Waiver of HIPAA Authorization or a HIPAA Authorization signed by the research subject or their Personal Representative.

5. The Privacy Act and Research • The Privacy Act governs federal agencies that collect, maintain, or use a system of records with personal information.  The Act: • prohibits agencies from disclosing information about “individuals” to “any person, or to another agency” without the individuals’ consent (absent certain exceptions); • gives “individuals” the right to review and copy agencies’ records about them; and • gives “individuals” the right to request amendment of records pertaining to them. • Main Takeaway: VA cannot disclose (release) identifiable information for non-permissible purposes without the subject’s written authorization. • Applies to all research involving human subjects, to include exempt research

6. Categorizing Projects • Review all details of the project • Address questions in the following order: • Is it research? • Is it human subjects research? • Is the study exempt from IRB review? • Is my facility engaged in human subjects research? • Can the IRB use the expedited review process?

7. Who can Determine if a Study is Exempt? • For VA research, the following individuals can make the exempt determination: • The IRB Chair • An experienced IRB member • Qualified Administrative Staff • The Investigator is not allowed to make exempt determinations • When required, limited IRB review must be conducted by the IRB (convened or expedited review) • ORPP&E is exploring the potential use of an electronic determination aid for exempt determinations • VA Electronic Determination Aid (VAEDA)

8. When Does a Study Qualify for Exemption: Exempt Categories • Research activities in which the only involvement of human subjects will be in one or more of the eight categories outlined in the Common Rule (38 CFR 16.104(d)) may be exempt from IRB review • All research activity(ies) must meet the requirements of the exempt categories selected • If limited IRB review is required, the IRB must determine that the limited IRB review criteria are met Refer to handout for a list of exempt categories

9. Limited IRB Review • Specific to Exemptions 2(iii); 3(i)(c); 7; and 8 • Can be conducted by Expedited Review • IRB is not required to make all the 111 approval criteria, instead… • For Exemptions 2(iii) and 3(i)(c) – IRB must ensure that adequate provisions exist to protect the privacy of subjects and maintain the confidentiality of their data • For Exemption 7: that Broad consent was obtained; broad consent was appropriately documented or waived; and if a change is made for research purposes in the way the identifiable information or specimens are stored, adequate provisions exist to protect the privacy of subjects and maintain the confidentiality of their data. • For Exemption 8: IRB must ensure that adequate provisions exist to protect the privacy of subjects and maintain the confidentiality of their data and that the proposed research is within the scope of the broad consent

10. What Oversight is Required for Exempt Research at the VA? • For exempt research requiring limited IRB review: • The VA Research and Development (R&D) Committee unless it is under the oversight of another subcommittee of the R&D Committee. • Once the IRB performs limited IRB review, the IRB has no further role (unless the exempt reviewer determines that the research is not eligible for exemption). • For exempt research not requiring limited IRB review: • The VA Research and Development (R&D) Committee unless it is under the oversight of another subcommittee of the R&D Committee.

11. Is Continuing Review Required for Exempt Research Activities? • The R&D Committee is responsible for both the initial approval and continuing oversight of exempt research unless it is under the oversight of another subcommittee. • Continuing review of exempt research may not exceed 365 days (VHA Directive 1200.01 paragraph 9d(1)(d)).

12. Exempt Studies: Additional VA Requirements Studies involving interactions with subjects or obtaining information by educational tests, survey or interview procedures, or behavioral interventions (VHA Directive 1200.05 para 10c): • Prospective subjects must be provided the following information, as applicable, in writing or orally: • The activity is research • Participation is voluntary • Permission to participate can be withdrawn • Permission for use of data can be withdrawn for exempt research activities involving the collection and use of identifiable data; and • Contact information for the VA Investigator • Particularly applicable to some of the activities within exempt categories #1, 2, and 3

13. Summary of Changes to Exemptionsin the Revised Common Rule Revised Common Rule (current) Pre-2018 Rule Restrictions added Expanded Removed and replaced with a new exemption 3 Expanded old and added new Expanded with changes No change *Exemption 7-NEW *Exemption 8-NEW • Exemption 1 • Exemption 2 • Exemption 3 • Exemption 4 • Exemption 5 • Exemption 6 Refer to webinar conducted by Dr. Kristina Borror on Changes in Exempt Categories: https://www.research.va.gov/pride/cyberseminars/RevisedCommonRule-091918.cfm

14. Applying Exempt Categories to Research involving Pregnant Women, Prisoners, and Children • Pregnant Women: All exemptions apply • Prisoners: Only applies if research is aimed at involving a broader subject population that only incidentally includes prisoners • Children: • Categories 1, 4, 5, 6, 7, and 8 apply • Categories 2(i) and 2(ii) only apply to research involving educational tests or observation of public behavior when the investigator(s) do not participate in activities being observed • Categories 2(iii) does not apply

15. Poll: Which Exempt Category Concerns You the Most when Making Determinations? • Exempt Category 1: Research in Established or Commonly Accepted Educational Settings • Exempt Category 2: Educational Tests, Surveys, Interviews, Observations of Public Behavior • Exempt Category 3: Benign Behavioral Interventions • Exempt Category 4: Secondary Research for which consent is not required

16. Exempt Categories 1 & 2

17. Exempt Category 1: 2018 Rule • Research conducted in established or commonly accepted educational settings, that specifically involves normal educational practicesthat are not likely to adversely impact students' opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods. (38 CFR 104d(1))

18. Exempt Category 2: Pre-2018 Rule Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects’ responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, or reputation. (38 CFR 101(b)(4))

19. Exempt Category 2: 2018 Rule Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met: (i) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects; (ii) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or (iii) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by § 16.111(a)(7).

20. Case 1 • A VA study team would like to conduct a study to explore the different methods by which medical residents receive training during their residency programs. • The study will be conducted at five (5) VA facilities and will involve the study team observing the way morning report sessions and morning rounds are conducted among various departments. Metrics will be collected on the way the sessions are conducted without any interference by the study team. No patient information will be recorded during the observations. • Residents will be invited to take part in interviews scheduled during their downtime to gather their opinions on the optimal format for delivering training. Residents identifiable information will be recorded (e.g. names, date of birth, current residency rotation).

21. Poll 1: Case 1 Would this study qualify for exemption? • Yes, Category 1 • Yes, Category 2 • Yes, Category 1 and 2 • No See notes for additional commentary.

22. Poll 2: Case 1 Would the study require limited IRB review? • Yes • No See notes for additional commentary.

23. Case 1 (continued) • Due to difficulty scheduling the interviews because of residents busy schedules, the study team proposes having subjects complete a survey instrument about their opinions on the optimal format of morning reports during 50 mins of the 60 minute scheduled morning report session. • Permission has been obtained from the Program Director to allow this one time administration of the survey during the time allotted for morning report.

24. Poll 3: Case 1 Does the study qualify for exemption? a. Yes, Category 1 b. Yes, Category 2 c. Yes, Category 1 and 2 d. No See notes for additional commentary.

25. Case Study 2 • An Investigator wants to better understand how Veterans diagnosed with PTSD seek out treatment and what coping mechanisms they use • The research involves an in person or telephone interview with the Veteran to explore different options for therapy and assess their receptivity to the various options • The interview will be audio-recorded and will include questions about illegal drug use • Subjects will sign a written HIPAA authorization for collection and use of their protected health information (PHI).

26. Poll 4: Case Study 2 Is this study eligible for exemption? a. Yes, exempt Category 2 without limited IRB review b. Yes, exempt Category 2 with limited IRB review c. No See notes for additional commentary.

27. Poll 5: Case Study 2 What are some of the things the IRB should consider when performing limited IRB review? • If research results will be returned to subjects • Whether the informed consent form includes information about the session being recorded • Whether the study should have a Certificate of Confidentiality (COC) • All of the above • None of the above See notes for additional commentary.

28. Exempt Categories 3 & 4

29. Exempt Category 3: 2018 Rule Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met: • (A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects; • (B) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or • (C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by § 16.111(a)(7).

30. Benign Behavioral Intervention Benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing (38 CFR 104(d)(3)(ii). • Examples provided include: • having subjects play an online game, • having subjects solve puzzles under various noise conditions, • having subjects decide how to allocate a nominal amount of received cash between themselves and someone else • Studies involving deception: Subjects must prospectively agree that they will be unaware of or misled regarding the nature and purpose of the research.

31. Exempt Category 3: Things to Consider

32. Case Study 3 • Adult subjects who suffered from a stroke are asked to take part in two sets of 1-hour non-interventional assessments of memory, attention, and information processing speed before and after performing 30 minutes of cognitive enhancement exercises using an ipad. • Subjects will provide verbal and written responses to the questions. • The sessions will be held on two-consecutive days (2.5 hours each day). • Assessments will be conducted privately with a study team member. • Subjects are encouraged to take breaks when desired. • Identifiable information will be recorded. • Subjects have signed a written HIPAA Authorization for collection and use of their PHI for research purposes.

33. Poll 6: Case Study 3 Does this study meet the requirements for a benign behavioral intervention? • Yes • No See next slide for breakdown of why we felt the study could be considered a benign behavioral intervention.

34. Case Study 3: Evaluation of Key Criteria

35. Case Study 3 (continued) • The investigator would like to capture whether stress caused by the cognitive enhancement exercise is confounding the results. • The Investigator proposes collecting blood pressure and pulse readings during the exercise, along with collection of a saliva sample to measure cortisol levels after the game is played. Q: Is the study eligible for exemption

36. Poll 7: Case Study 3 Is the study eligible for exemption? a. Yes b. No See notes for additional commentary.

37. Exempt Category 4: Pre-2018 Rule Research, involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects (38 CFR 101(b)(4)).

38. Exempt Category 4: 2018 Rule Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met: (i) The identifiable private information or identifiable biospecimens are publicly available; (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;

39. Exempt Category 4 (continued) (iii) The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or (iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non-research activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501et seq.

40. Case Study 4 • Dr. See submits a protocol to the Lexington VA IRB to conduct human research on patients treated for hepatitis at the hospital over the next 5 years. • Aim 1 of the study will be to understand clinical disease progression. Subject medical record numbers will be recorded and used to cross reference patient’s microscopic images, lab reports, and information from subject’s medical records. • Aim 2 of the study involves detection of certain biomarkers indicative of early stage hepatitis disease. • Identifiable biospecimens with accompanying data will be purchased from a for-profit repository for this effort. The specimens obtained are not related to the subjects included in Aim 1 of the study.

41. Poll 8: Case Study 4 Does this study qualify for exemption (check all that apply). • Yes – Category 4(i) • Yes, Category 4(ii) • Yes, Category 4(iii) • Yes, Category 4(iv) • No See notes for additional commentary.

42. Case Study 5 • A VA researcher is investigating the incidence of a certain cancer on Veterans who were deployed during Operations Iraqi Freedom and Enduring Freedom • 5 VAs will be involved in this chart review study • Identifiable information will be obtained and recorded from CPRS (VA’s electronic medical record system) • The Privacy Board has approved a waiver of HIPAA Authorization for the study

43. Poll 9: Case Study 5 Is the study eligible for exemption? • Yes, exempt category 4 • No See notes for additional commentary.

44. Poll 10: Case Study 5 Should the IRB perform a limited IRB review to ensure that there are adequate provisions in place to protect the privacy of subjects and maintain the confidentiality of their data? a. Yes b. No See notes for additional commentary.

45. Case Study 5 (continued) The study team would like to send the identifiable data to a co-investigator at Fred Hutchinson Cancer Research Center who will analyze the identifiable data and compare it with a dataset obtained from one of their repositories on age-matched cases of Civilians who were not deployed during the similar timeframe. Q: Can the identifiable data be sent to the co-investigator at the Fred Hutchinson Cancer Research Center?

46. Poll 11: Case Study 5 Can the identifiable data be sent to the co-investigator at the Fred Hutchinson Cancer Research Center? a. Yes b. No See notes for additional commentary.

47. Questions

48. Important Links • Final Rule for the Delay (published June 19, 2018) • Revised Common Rule (published January 19, 2017) • Pages 7259 to 7274 contain the Text of the Final Rule • Current Common Rule • VHA Handbook 1200.05 • ORD Policies and Guidance Documents • ORPP&E Cyberseminars