1. MARK A. JAMES, Ph.D. Chair, Biomedical IRB TULANE UNIVERSITY Ethics in Global Health Research: Role of the Tulane IRB

2. Role of the Tulane IRB Introductions Biomedical and Social/Behavioral IRB Functions of the Tulane IRB Responsibilities of the IRB in Global Health Research Questions from the Research Community

3. Institutional Review Board (IRB) Tulane University: 2 IRB (Biomedical, Social/Behavioral). Comprised of at least 5 members. Diverse expertise/different professional specialties (scientific and nonscientific). Sensitive to and knowledgeable about community attitudes and vulnerable subject populations. Knowledgeable of institutional commitments, regulations, applicable laws, and standards of professional conduct with regard to research.

4. Code of Federal Regulations: “Common Rule” and Food and Drug Administration (FDA) Common Rule: Effective August 19, 1991 Adopted by 19 Federal Agencies Based on 45 CFR 46, subpart A; located at: http://www.hhs.gov/ohrp/humansubjects/guida nce/45cfr46.htm FDA: for drugs and medical devices, based on 21 CFR 56, subpart A.

5. Basic Requirements and Vulnerable Populations Subpart A – Core Requirements Subpart B – Pregnant Women, Human Fetuses, and Neonates Subpart C - Prisoners Subpart D - Children

6. Practice vs. Research—Belmont Report  Practice: “Interventions that are designed solely to enhance the well-being of an individual patient [or community] that have a reasonable expectation of success.”  Research: “Designates an activity designed to test an hypothesis, permit conclusions to be drawn and thereby to develop or contribute to generalizable knowledge.”

7. Biomedical Research Research that is conducted to contribute to an increased understanding of disease processes, new treatments and interventions, and the prevention and control of infectious and chronic diseases in clinical medicine and public health; and research involving human biological specimens (i.e. collecting or accessing tissues or genetic material for research purposes).

8. Social/Behavioral Research Research involving the study of social and behavioral human functioning at the individual, small group, institution, or community levels. The study of behavioral factors such as thought processes, personality and emotion; also, the study of social and environmental variables are examples. Methodologies include direct observation, interviews and surveys etc.

9. Basic Functions of the IRB Protect welfare of human research participants. Ensure Institutional compliance with federal regulations. Provide guidance to facilitate investigator’s compliance with federal and state regulations in conducting human research. Provide a process for investigators to submit protocols for review.

10. Belmont Report: Basis Ethical Principles Respect for Persons: Autonomy—informed meaningful choice; free from outside influence. Beneficence: Above all, do no harm. Always consider the risk/benefit ratio for study participants. Study is designed so that risks are minimized. Justice: Distribute the risks and potential benefits of research equally among those who may benefit from the research. Vulnerable subjects are not targeted for convenience.

11. Major Considerations Scientific and ethical review: --confidentiality/right to privacy --participation does not conflict with right to primary health care --risks do not exceed potential benefits --appropriateness of informed consent and research protocols Diversity of IRB members important!

12. Review Types & Examples Exempt – excluded from further IRB review  Analysis of secondary data, anonymous surveys, etc.  No data that can link to identity of study participants. Expedited – no greater than minimal risk  Interviews, surveys, retrospective chart reviews, etc. Full Board – greater than minimal risk  Significant risk/benefit ratio; vulnerable populations; sensitive questions; invasive medical procedures, etc.

13. Core Requirements for Approval of Research Risks to subjects are minimized. Risks to subjects are reasonable in relation to anticipated benefits. Selection of subjects is equitable. Informed consent will be sought from each perspective subject. Informed consent will be appropriately documented. Data safety monitoring. Adequate provisions to protect the privacy of subjects and maintain the confidentiality of data.

14. Analysis of Risk What are the known risks of the research in consideration of subject characteristics? What is the probability (based on available empirical data) that any given risk will occur and what is the magnitude of the harm or discomfort? What procedures/changes are necessary to minimize risk?

15. Definition of Minimal Risk Minimal risk (MR) means that the probability and magnitude of harm or discomfort (the subjects may experience that is) anticipated in the research (as a whole) are not greater in and of themselves than those (reasonably foreseeable, low intensity, harms or discomforts) ordinarily encountered in the daily life (of average persons in the general population) or during the performance of routine physical or psychological examinations or tests.

16. Examples of Interventions by Risk Classification No more than minimal: Blood sampling (vp) Urine collection MRI Routine x-ray Standard psych testing Sexual history survey Greater than minimal: Indwelling IV catheter Urinary catheter MRI, IV contrast CT scan Extensive psych tests Sexual abuse survey

17. Informed Consent “Ethical research on people cannot take place in a vacuum.” Subjects must consent to participate in research; usually written but may be oral consent. Research subjects are participants in the study and should be allowed to ask questions about the protocol. Subjects retain the right to voluntarily withdraw from the study, at any time, for any reason. Subjects should be informed of the research findings at the completion of the study.

18. Subpart D: Additional Protections for Children as Research Subjects If not greater than minimal risk, assent of child (ages 7-17 years) and permission of parents are obtained. If greater than minimal risk but prospect of direct benefit to subject: (1) risk justified by benefit; (2) risk to benefit ratio as favorable as alternative approaches; (3) assent of child and permission of parents required.

19. Requirements for Permission by Parents and for Assent by Child (IRB Determination) If IRB determines that child is capable of assent, adequate provisions should be made for such. Look at age, maturity, and psychological state. Can be done for all participants or on a case-by-case basis. If assent not possible, but direct benefit available only in context of research, assent of child not necessary to proceed with research. Parental consent of both parents needed, unless not possible. If protocol is designed for conditions or for a subject population for which permission is not a reasonable requirement (ex: neglected or abused children), consent of parents may be waived; “emancipated” minor (important in the global context).

20. Cultural Competency Culturally-competent consent form:  Individual consent.  Family consent-secondary subjects.  Community consent.  Mechanisms for protection of privacy and confidentiality defined in the consent form or information sheet.

21. Research Ethics in the Global Context Responsibilities of the local Ethics Committee: --Assessment of interventions—safe, scientifically sound; research is relevant to the local community; training and experience of researchers; conditions at research site. --Membership: persons familiar with the customs and traditions of the community.

22. IRB and Global Health Research Obtain approval of local authorities: local Ethics Committee; Ministry of Health, regional health authorities, community leaders. Submit documentation to the IRB. Translate all documents (informed consent, protocols, questionnaires) into the local language. Letter of certification of authenticity of translation is required (independent of research team).

23. Biomedical IRB Actions: 2006-2008 July 1, 2006 - June 30, 2007 Continuing Reviews 334 Initial Submissions 136 Adverse Events and Procedures 60 Expedited Reviews 1214 Exempt Reviews 54 Total Actions Per Year 1798 July 1, 2007 - June 30, 2008 Continuing Reviews 567 Initial Submissions 150 Adverse Events and Procedures 514 Expedited Reviews 1280 Exempt Reviews 76 Total Actions Per Year 2587

24. Current Open Protocols: 05/12/09 Biomedical IRB = 802 Social/Behavioral IRB = 167 Total Open Protocols = 969

25. Questions from the Research Community Q1: Project gets “exempt from review” status from Tulane IRB (Tulane PI, Tulane IRB). A Tulane student wants to do a data analysis with these data with no personal identifiers, do they apply for “exempt from review”? Or since the project was “exempt from IRB review”, maybe they don’t need to apply? What if the student is not at Tulane? A1: The IRB determines whether a study qualifies as Exempt. Thus, one must be careful when using the term “exempt from review.” In this case, the Tulane student should submit another Exempt application. The student may be the investigator of record; a Faculty Sponsor (Form A) is required. If a Tulane student is conducting human subjects research at another site, the research must be IRB-approved. Independent research by a non-Tulane student researcher is beyond the purview of the Tulane IRB, but his/her research activities would be subject to the same ethical standards at another university/IRB.

26. Questions from the Research Community Q2: What type of review does a student who wants to do secondary data analysis with data with no identifiers have to apply for? A2: As stated in the answer to the previous question, the student would apply for Exempt status with a Faculty Sponsor (Form A).

27. Questions from the Research Community Q3: As faculty at Tulane, I am sometimes asked to participate in the write up of a student/colleague’s research project – often once the data has already been collected and analysis is underway or finished. As long as the project has IRB approval from local/US institutions with FWA, do I also need to get IRB approval from Tulane? (two scenarios: one in which I am not seeing or analyzing data? What about if I am actually seeing the data?). A3: The Tulane faculty member would not be required to submit to our IRB to participate in manuscript preparation in which possible further analysis of the data is presumed.

28. Questions from the Research Community Q4: It is our understanding that departmental representatives are asked to leave the room when IRB protocols from their own department are discussed. This appears counter-productive, as this is the person who is most likely to provide clarifications about the protocol. A4: The IRB does not have departmental representatives. The committee membership consists of individuals with varied specialties and disciplines across schools to facilitate discussion of all protocols under review. If an IRB member is an investigator on a protocol under consideration, he/she must recuse themselves prior to any discussion. In addition, if a committee member has a perceived or indirect conflict (e.g. department chair, etc.) with a protocol, the member may contribute to the discussion but abstain from the vote.

29. Questions from the Research Community Q5: Sometimes IRB gives feedback that is inconsistent. For example, a protocol/consent form may have been approved for a particular study, but when the study is later on replicated in another location, the same protocol/consent form is not deemed adequate. In such cases, how can the PI formally appeal, with out having to incur the one-month delay that is associated with a re-submitting for a subsequent IRB meeting? A5: We apologize for any inconsistent responses. Our processes may seem cumbersome, but any new information and forms, etc. are designed to improve compliance with federal regulations in assuring optimal protection of human research participants. Any modifications to the protocol and/or consent form, including a new performance site or investigator, require submission of an amendment request with revised protocols and consent forms (new version date). Such modifications are reviewed under Expedited status; turnaround time should be no more than a couple of weeks now with two Biomedical IRB meetings per month.

30. Questions from the Research Community Q6: When conditional approval is granted, the concerns tend to be minor. Often such concerns are actually minor things that the board did not fully understand, and that easily could have been explained by the PI. The current procedures require that the PI resubmit for the next meeting, which implies a one-month delay (longer if it is during the summer). Why doesn't the IRB give the PI the opportunity to make him/herself available on the day of the meeting, so that the IRB can call him/her in if needed to explain/resolve these minor issues on the spot? A6: Minor revisions to the protocol or consent form are now referred to as “Deferred Pending Minor Revisions/Modifications.” Submission of a response and revised documents is reviewed under Expedited status, generally in 1 to 2 days by the Chair. If a study is “Deferred Pending Major Modifications,” the application is often incomplete or substantial clarification is needed. In this case, the study must be reviewed at the next full board meeting. For questions regarding the study design itself, the investigator may be consulted prior to the meeting or by phone, if necessary, during a convened meeting. It is important to remember that IRB members are volunteers who spend a significant amount of time reviewing protocols and attending IRB meetings. The HRPO tries to keep the length of meetings as short as we possibly can, and our experience has been that having the PI’s present at the meetings significantly extends the length of the meetings.

31. Questions from the Research Community Q7: Sometimes a conditional approval will have very specific instructions for the PI (e.g., on the consent form, rephrase "x" to "y"). When the instructions are this specific, what is the benefit of asking the PI to re-submit the revised application for review at the next meeting? Would it be a more effective, both for the study and for the IRB, to simply instruct him/her to make these changes before starting data collection? A7: Again, studies “Deferred with Minor Modifications” may be reviewed under Expedited status by the Chair. Once the modified application is submitted to the HRPO, the documents can be reviewed and approved. All documents must be complete and accurate prior to granting final approval of a study. Research activities are not permitted until final approval is granted.

32. Questions from the Research Community Q8: When a study is open for data analysis only, a continuing review is required each year. Given that no data are being collected, the continuing review is identical each year. When the continuing review is for data analysis only, wouldn't it be more efficient for both the PI and IRB to establish a continuing review for 3 or 5 years, or even indefinitely? A8: The period for continuing review cannot be longer than 1 year. This is a federal requirement that ensures timely oversight of research studies. With studies where risks to participants are greater than minimal or with an inordinate number of severe adverse events, continuing review may be more frequent, e.g. 6 months.

33. Questions from the Research Community Q9: The consent forms that Tulane IRB typically requires are very long and quite complex. Often the consent form is nearly a page long, single spaced. As a result, the majority of respondents in a developing country will not understand them. This appears to go radically against the intent to protect human subjects. By contrast, some of the most reputable survey programs use a very short and simple consent statements (2-3 lines) that respondents can clearly understand. If the purpose of the consent form is to protect human subjects, what is the reason that consent forms that satisfy the IRB requirements of the most reputable survey organizations are deemed unacceptable by the Tulane IRB? A9: The Tulane consent template is designed to maximize the protection of study participants should they choose to participate in a research study. Sections in the template that do not apply to the study may be omitted. It is important that the consent form be understandable to a person with an 8 th grade education level. Under certain circumstances, an oral consent process may be used instead of the standard written informed consent form. A shorter consent form will be considered when recommended by the local ethics committee.

34. Questions from the Research Community Q10: IRB procedures appear to have been developed with NIH studies in mind. However, many faculty members engage in activities that do not fit this model. For example, a faculty member may have funding for a large project, which may include several unrelated studies that are each headed by a different investigator. Often the faculty member who heads the overall project has no involvement whatsoever in these research studies. Yet, IRB sometimes (but not always) insists that the PI of the overall project is also responsible for each of the studies. This is inconsistent with the views of the donor. More importantly, it implies that critical IRB information is mailed to a person who has no involvement in the study. This is a highly questionable approach for ensuring the protection of human subjects. There is a need for a formal mechanism that enables the actual study investigator (rather than the PI of the larger project) to apply for IRB approval. A10: Often sub-studies or program projects are submitted to the IRB with study-specific investigators under a previously approved umbrella study. The sub-studies are considered as new initial submissions. Each PI may designate a second person, i.e. research coordinator, to whom all IRB correspondence will be forwarded.

35. Questions from the Research Community Q11: I'm a qualitative social scientist at the SPHTM whose research involves in-depth interviews and observational research on judgment samples of study participants. Much of the biomedical forms and procedures are not applicable, as well as being cumbersome to fill in. Submitting would seem to be an unnecessary burden on a busy biomedical IRB. Can I apply to the uptown Social-behavioral IRB? (if not, why not?) A11: All applications for the use of human subjects in research are submitted to the same office (HRPO) and then assigned to the respective IRB. Although all public health research has traditionally been assigned to the Biomedical IRB as part of research at the Health Sciences campus, we are not opposed to the use of the Social/Behavioral Initial Submission form. Please be reminded that the Biomedical IRB does have expertise on the committee to enable review of public health research studies.

36. Questions from the Research Community Q12: What is the relevance of the source of funding/sponsorship to the review of human subjects research as an “ethical” concern? I am proposing to do small-scale formative research for which I lack sponsorship, in order to strengthen research proposals. What is the IRB position on that? A12: The sponsor has a critical multifaceted role in the conduct of research studies, especially clinical trials adherent to Good Clinical Practice in ensuring the safety and well-being of study participants. In addition, investigator/sponsor relationships are important for “Conflict of Interest” issues which may require a statement of disclosure to potential study participants. Research applications may be submitted without an external funding source. Often researchers will submit “Investigator-Initiated” applications that lack sponsorship. Approval by section heads/department chairs is required to ensure appropriate scientific merit of the study.

37. Questions from the Research Community Q13: What is the IRB interest in power calculations of sample size? I can understand this is a concern for peer-review grant processes in determining the quality of the research design. In what specific ways are these statistical calculations (and the epistemological assumptions underlying these) an particular issue of the IRB and its task of reviewing ethical dimensions of research involving human subjects? A13: An inappropriate study design, in this case an inadequate sample size, may increase the risk/benefit ratio for study participants, when statistically significant conclusions to the study will never be achieved. One responsibility of the IRB is to ensure that subjects are not placed needlessly at risk/harm during any study. The Tulane IRB membership includes biostatisticians who lend expert opinion in such instances.

38. Questions from the Research Community Q14: Who developed these forms--are they national, federal forms, or just Tulane? Perhaps we could get some forms & procedures from other major research universities. A14: The forms and procedures in use by the HRPO and its IRB are Tulane-specific that ensures institutional compliance with federal regulations. However, all research institutions, especially those with an accredited IRB, adhere to the same federal requirements in the protection of human research participants. Modifications to our processes are likely as we continually work to enhance compliance with federal guidelines, especially as we move toward formal accreditation. Please be reminded that when we move to an electronic submission process (IRBnet) in the coming months, the present forms may become obsolete.

39. Questions from the Research Community Q15: I do research with prisoners so having a prisoner rep on board and the policy for dealing with this is of upmost concern for me. A question would be: What are the procedures for reviewing application with special populations - i.e. prisoners; are they familiar with this process and have they done it in the past? Do they have specific suggestions for the protocol? A15: Review of studies involving prisoners as study participants requires a prisoner representative as a member of the convened committee. These persons are regular members of the IRB and serve as an advocate for the prisoner population. As such they have experience with this population, particularly as research subjects, since participants may be vulnerable to coercion. The prisoner committee representative would carry out the review and lead discussion of the protocol in the same manner as with any other type of research study under consideration by the IRB.

40. Questions from the Research Community Q16: Scenario: I want to do a pilot of say 10 people with very limited funds to show the feasibility of the logistics of recruiting and retaining people released from prison. A larger grant I applied for liked the idea but wanted to see the feasibility. So I am doing this with basically no budget - recruiting the people myself. Would I then have to pay IRB to review this pilot when I am working with limited funds? A16: Investigators frequently submit “Investigator-Initiated” projects as pilot studies while seeking external funding. As stated above, the IRB would review your study with the assistance of the prisoner representative. The IRB would not charge a fee as it only assesses fees for initial submission and continuing review of industry-sponsored studies.

41. Questions from the Research Community Q17: Do I need IRB approval if I am going to do content analysis research using essays, tests or documents that were submitted by students one year ago as part of a class, where I am not the teacher? Of course, names of students (emails and any other personal information) will be previously removed and the report will be about the topics and answers included on those documents, not about the students as human subjects. A17: This type of study would need to be submitted to the IRB, however it would qualify as Exempt since all identifiers have been removed.

42. Questions from the Research Community Q18: Do I need IRB approval to apply an anonymous pre-test and post-test survey (using a matching code) to students in a class, before and after a lecture, which is not graded as part of a class? A18: It depends on the nature of the survey. If the survey is being carried out solely as an evaluation tool to improve course content or teaching quality, then use of this survey is beyond the purview of the IRB. However, if the survey is targets another topic outside of the regular course content, and especially if it is designed as a systematic investigation, then IRB approval is required. The nature of the review—exempt vs. expedited—would depend on the survey methodology.

43. Questions from the Research Community Q19: What are the IRB implications of Tulane faculty serving as external consultants on non-Tulane research projects? A19: Consultancies will be reviewed on a case-by-case basis; however, the general rule is that the Tulane IRB will not be the IRB of record if an investigator is acting as a consultant outside his/her scope of employment with the university.

44. Nature and Scope of IRG Activity