Risk Mitigation in Mixed SBER and Biomedical Research

1. Risk Mitigation in Mixed SBER and Biomedical Research The SBER Subcommittee of The Harvard Catalyst’s Regulatory Foundations, Ethics, and Law Program Thursday, November 15th, 2018

2. Presenters http://catalyst.harvard.edu/programs/regulatory/sber.html • Matt Stafford, Assistant Director for Clinical Research Compliance at Boston Children’s Hospital, and Co‐Chair of the Harvard Catalyst Social Behavioral Educational Research (SBER) Committee • Lara Sloboda, PhD, CIP, SBER IRB Operations Manager at Tufts University • Alma Castro, MA, CIP, IRB Review Specialist at Harvard T.H. Chan School of Public Health

3. Presentation Outline • Using case studies, this session will focus on risk mitigation in research involving both biomedical and social science methods. Case studies will include piloting initiatives to overcome reluctance to utilize support/recovery services for persons affected by opioid abuse, and an evaluation of an early intervention program to ameliorate psychosocial effects of Chronic Traumatic Encephalopathy in youth who play contact sports. Attendees should have a basic foundation in human research protections ethics and principles, including the criteria for approval and definitions from DHHS and FDA regulations before attending this session. During this session, speakers and attendees will: http://catalyst.harvard.edu/programs/regulatory/sber.html

4. Learning Objectives • Review the nature of the risks, harms, and impacts associated with mixed SBE/biomedical research • Explore factors likely to contribute to increased risk in research spanning both medical and social/behavioral arenas • Discuss how to design research with sufficient protections and minimize risk through study design http://catalyst.harvard.edu/programs/regulatory/sber.html

5. IRB Responsibilities http://catalyst.harvard.edu/programs/regulatory/sber.html • Identify Risks • Determine that risks are minimized • Determine that “risks to subjects are reasonable in relation to anticipated benefits” • Determine that subjects are adequately informed about “any reasonably foreseeable risks or discomforts”

6. Nature of Risk http://catalyst.harvard.edu/programs/regulatory/sber.html • Risk in Biomedical Research: • Often predictable a priori • Easier to identify • Probability of harm is predictable but not controllable • Social & Behavioral Risks are: • Time and situation specific • Variable • Very subjective • Less predictable than many biomedical risks • Often unknown (there is little or no empirical data on the likelihood of risk in behavioral or social research)

7. Nature of Risk http://catalyst.harvard.edu/programs/regulatory/sber.html • Assessment of risk for biomedical research often diverges from social behavioral research • If standards for biomedical research are used to assess risk, social behavioral research risks may go unnoticed, and vice versa • Triangulation of data. • Research using different methods and perspectives address different problems creating stronger results, however there are issues with each approach.

8. Risks in Mixed SBE and Biomedical Research http://catalyst.harvard.edu/programs/regulatory/sber.html Commonalities in research • Autonomy and beneficence are respected • How will research affect the subjects’ lives ? • How aware of the nature, intentions and both personal and public outcomes of the research are participants? • The level of discomfort caused by the research in these terms has to be set against beneficence.

9. Risks in Mixed SBE and Biomedical Research http://catalyst.harvard.edu/programs/regulatory/sber.html Considerations for Risk Assessment • Biomedical research traditionally has not used qualitative data collection techniques • Larger magnitude of risk in biomedical research than social research • Social research methods may magnify risks in biomedical research

10. Risks in Mixed SBE and Biomedical Research http://catalyst.harvard.edu/programs/regulatory/sber.html • Methodology specific to SBE and Biomedical Research activities alter risk assessment • The confluence of the two possibly lead to enhanced risk • Risk of confidentiality influenced by nature of data being collected • Economic or legal harm may be more greatly affected by methodological considerations • HIPAA considerations may be different with involvement of biomed research

11. Risks in Mixed SBE and Biomedical Research http://catalyst.harvard.edu/programs/regulatory/sber.html • Anxiety and distress • Exploitation • Misrepresentation • Identification of the participant in published papers, by themselves or others.

12. Impact of Research http://catalyst.harvard.edu/programs/regulatory/sber.html • What is a reasonable expectation of privacy? • Is the population or topic of research particularly stigmatized? • Are protections for third parties necessary? • Deferential vulnerability, timing of the research may lead to undue influence. • Investigators may encounter situations that require reporting such as abuse which investigators have legal obligation to report. • Alternatively, might there be protective effects for participants in research?

13. Evaluation of Risk/Benefit Ratio http://catalyst.harvard.edu/programs/regulatory/sber.html • IRB must decide whether the anticipated benefit justifies asking subjects to undertake the risks • Should take into account different subject populations and individual differences among subjects • Should consider whether there exist alternative procedures of collecting data to minimize risk • Justification of sample size • Proper exclusion criteria • Data monitoring for patient safety

14. Minimizing Risk in Research Design http://catalyst.harvard.edu/programs/regulatory/sber.html • Mechanisms to minimize risk: • Understand particular challenges associated with participant group • Consent requirements • Require timely scoring/review of mental health assessments • Appropriate safeguards to protect data • Require post-approval monitoring • Researcher expertise • Create plan for dealing undesirable events • ensuring scientific soundness • organizing follow-up care where appropriate • ensuring confidentiality by taking a reflexive stance towards analysis.

15. Special Considerations & Challenges http://catalyst.harvard.edu/programs/regulatory/sber.html • Researchers must consider factors likely to contribute to increased risk and how it can impact not only the conduct, but also the interpretation of the research. • Through greater understanding of risk assessment, researchers can better equip themselves with the necessary skills to enhance effectiveness and ability to reduce the possibility of harm, while employing best practices to minimize risks and inform subjects about them.

16. Breakout Groups • 1. Choose spokesperson/reporter for your group • 2. Each group focuses on one or two aspects of the protocol • 3. Discuss protocol for 10 minutes • 4. Respond to the following questions  • 5. Spokesperson will report to workshop • What are the issues raised in your protocol section? • How has researcher addressed them? • What is positive about researcher’s protocol in this area? • What is in the ‘grey area’ of the protocol in this area? • Could board ask any additional questions of the researcher to clarify the “grey area”? • Could board make any helpful suggestions to strengthen the protocol in the area of concern? http://catalyst.harvard.edu/programs/regulatory/sber.html

17. A Social, Behavioral, & Educational Research (SBER) Case Study of Medication Adherence and Destigmatizing Opioid Recovery Services by Amy Ben-Arieh and Matt Stafford with the SBER Subcommittee of Harvard Catalyst’s Regulatory Foundations, Ethics, and Law Program http://catalyst.harvard.edu/programs/regulatory/sber.html

18. Breakout Group Discussion • What are the issues raised in your protocol section? • How has researcher addressed them? • What is positive about researcher’s protocol in this area? • What is in the ‘grey area’ of the protocol in this area? • Could board ask any additional questions of the researcher to clarify the “grey area”? • Could board make any helpful suggestions to strengthen the protocol in the area of concern? http://catalyst.harvard.edu/programs/regulatory/sber.html

19. Medication Adherence and Destigmatizing Opioid Recovery Services Questions/Comments for the researcher: • How will individuals be consented for participation in the focus groups? • Considering that inclusion criteria for this group is opioid use disorder, how will you determine if a subject is able to consent to participate? Might the capacity for consent change over time? How should continued consent be assured and documented? • Will the focus groups be audio recorded? When will audio recordings be transcribed? When will they be destroyed? • Is information in the cloud and on the reader secure? http://catalyst.harvard.edu/programs/regulatory/sber.html

20. Medication Adherence and Destigmatizing Opioid Recovery Services Questions/Comments for the researcher: • What would happen if the reader or phone are hacked or stolen? • Given the sensitive intersection of identities, and the understanding that they carry stigma, could a more private method of discussion achieve the same/similar aims without risk of outing? • What are the protections for the electronic information as it is stored and analyzed on the cloud? http://catalyst.harvard.edu/programs/regulatory/sber.html

21. Medication Adherence and Destigmatizing Opioid Recovery Services Questions/Comments for the researcher: • If stigma is preventing this patient population from accessing group services, will passive recruitment be sufficient to get focus group Subjects? • Is a letter in the patient portal the right way to make first contact? • Who will be conducting the focus groups and/or study visits? • Will monitoring adherence impact adherence in the control group? • Will the content of the enhanced messages place subjects at risk? http://catalyst.harvard.edu/programs/regulatory/sber.html

22. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html Questions for the IRB: • What are the security/HIPAA concerns related to digital pill use? • Does the institution need a BAA with the digital pill/cloud server/phone app company? • Should age inclusion criteria be added? • Should the study seek a Certificate of Confidentiality from the NIH (not an NIH funded study)?

23. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html Questions for the IRB: • Should written consent for participation in the focus group be waived? • Is provision of a smart phone and/or payment for this extremely expensive medication an undue inducement to participation? • How might alterations to the study design lower risk to subjects? • What are the procedural risks of this study?

24. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html Questions for the IRB: • While the HCV medication is approved and standard of care, does combining with the digital pill make this an FDA regulated study? Are additional determinations required (e.g., non-significant risk)? • What training should be required for the study staff responsible for facilitating the focus groups? • What are the physical security details associated with the study smart phone and reader (e.g., storage of the device, access to it)?

25. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html • Alternate Detail: • Passive recruitment is insufficient, so the investigator submits an amendment seeking to give $5 gift cards to enrolled subjects who refer a potential Subject who completes screening (snowball/chain-recruitment). • .

26. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html • Other Events: • A recording device with the audio interviews is stolen. • Subject loses their phone.

27. An Evaluation of an Early Intervention Program to Ameliorate Psychosocial Effects of Traumatic Brain Injury (TBI) in Collegiate Athletes by Lara Sloboda and Matt Stafford with the SBER Subcommittee of Harvard Catalyst’s Regulatory Foundations, Ethics, and Law Program http://catalyst.harvard.edu/programs/regulatory/sber.html

28. Breakout Group Discussion • What are the issues raised in your protocol section? • How has researcher addressed them? • What is positive about researcher’s protocol in this area? • What is in the ‘grey area’ of the protocol in this area? • Could board ask any additional questions of the researcher to clarify the “grey area”? • Could board make any helpful suggestions to strengthen the protocol in the area of concern? http://catalyst.harvard.edu/programs/regulatory/sber.html

29. Medication Adherence and Destigmatizing Opioid Recovery Services Questions/Comments for the researcher: • Will participants be able to provide the information needed for eligibility with 48 hours of the concussing event? • If the research team is not referred to a potential participant immediately, will this affect the outcome of the study? • Will the requirements for enrollment in to the study contradict the potential participants’ doctor’s orders? • If participants are only referred by the coaching staff or Health Services, will their personal doctors be made aware of their enrollment in the research? • Are there any exclusion criteria, including assessing whether an injury is too severe to be eligible? http://catalyst.harvard.edu/programs/regulatory/sber.html

30. Medication Adherence and Destigmatizing Opioid Recovery Services Questions/Comments for the researcher: • What is the justification for collecting health information both through self-report and student health records? Both carry risks (confidentiality around health information, putting the participant in a stressful situation post-concussion). Is there a reason why both are necessary? • Is the participant able to consent to the study immediately following the concussion? Has the research team a means of identifying whether participants are able to consent, and if not, will the research team involve a Legally Authorized Representative? • Will the research team be looking into academic performance? Will the time effort needed for the study affect the students’ work load and academic performance? http://catalyst.harvard.edu/programs/regulatory/sber.html

31. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html Questions for the IRB: • Does this study qualify for a waiver of documentation of consent and a Health Insurance Portability and Accountability (HIPAA) waiver? • Who is conducting each aspect of the research? While there is a collaborative study team, who will be conducting the intervention? Does this individual have the training to be able to ensure the safety of the participants? • Is there any control comparison in the study? The study is a within subjects design, but is there any reason to think that there will be measurable results over such a short duration? • Are participants being asked to do too much following a brain injury? Are there ways to assess the effectiveness of this intervention in other ways?

32. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html • Alternate Detail: • In order to determine whether participants are eligible to return to sports, athletes will undergo an exertional test including running to determine if symptoms occur. They will also fill out a symptomology index. Only when symptoms are no longer present at baseline or after the exertional test will athletes be allowed to return to their sport. • The study team determines that some participants will be allowed to return to sport earlier than the school’s concussion protocol usually allows if they agree to being in a concurrent research study, since clinic and coaches agree that the extra monitoring may make it safer to resume athletic activities. The concurrent study includes audio-taping the athletes reading a pre-determined script to monitor changes in speech patterns over time. The use of speech patterns will help the researchers identify any micro-changes in word usage which could be indicative of long-term mTBI damage leading to CTE.

33. Medication Adherence and Destigmatizing Opioid Recovery Services http://catalyst.harvard.edu/programs/regulatory/sber.html • Other Events: • After being allowed to return to sport, a participant suffers another head injury. The research team determines that the participant should be removed from the study protocol because, having suffered two concussions in succession, the participant is no longer comparable to other participants. • While enrolled in the study, a research participant is arrested for public intoxication and aggravated assault. Individuals known to the participant report that both drinking and aggressive behavior are not typical of this individual. The clinical psychiatrist indicates that the criminal proclivity is likely a side-effect of the concussion.

34. Your Feedback Matters • We are committed to providing information that is openly accessible to investigators, institutions, and community partners for education and training purposes. • We are interested in constantly improving and updating our materials. • If you have any suggestions about this material, please contact us at: regulatory@catalyst.harvard.edu. • For additional information about SBER and the SBER Subcommittee visit: • http://catalyst.harvard.edu/programs/regulatory/sber.html http://catalyst.harvard.edu/programs/regulatory/sber.html

35. Resources http://catalyst.harvard.edu/programs/regulatory/sber.html • National Science Foundation: http://www.nsf.gov/bfa/dias/policy/human.jsp • American Anthropological Association: http://aaanet.org/cmtes/ethics/IRB.cfm • Certificates of Confidentiality Kiosk:http://grants1.nih.gov/grants/policy/coc/index.htm • NIH Office of Behavioral and Social Sciences Research: http://obssr.od.nih.gov/index.aspx • Harvard Catalyst Website: http://catalyst.harvard.edu • Introduction to Behavioral Science: https://www.youtube.com/watch?v=7_4o26enmGs • Behavioral Sciences (HS102): http://www.slideshare.net/jogiitr/behavioral-science

36. Citing These Slides • We encourage you to reproduce and use these materials freely. In doing so, we require that you acknowledge Harvard Catalyst as the publisher and give appropriate credit to the individual authors. • This material is the work the Harvard Catalyst Social, Behavioral, and Education Research (SBER) subcommittee. The SBER subcommittee is a subcommittee of the Regulatory, Law and Ethics Program and affiliated with Harvard Catalyst | The Harvard Clinical and Translational Science Center. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. • For additional information about citing support: • http://catalyst.harvard.edu/about/citingsupport.html http://catalyst.harvard.edu/programs/regulatory/sber.html