1. Providing Research Results to Participants David Shalowitz Department of Clinical Bioethics National Institutes of Health Pre-conference Program: Advanced Research Ethics October 28, 2004

2. Definition Results: Data collected about a given participant during the course of research— i.e. individualized results.

3. Case #1 Investigators discover that two siblings have a gene preliminarily associated with a disease that may cause loss of visual acuity or blindness. If pathology is identified early, vision loss can be prevented. Should investigators inform the siblings of the findings? Does it depend on the type of study?

4. Case #2 Investigators are conducting a large epidemiological study to determine whether various factors (social, economic, genetic) are associated with a greater risk for the development of heart disease. Should the investigators notify participants of potential risk factors at the conclusion of the study? What if a participant requests his or her results?

5. Disclaimer The views expressed in this presentation do not represent the official policies of the NIH, DHHS or the USPHS.

6. What are researchers’ responsibilities to participants? Pure Clinical Model Act to maximize the health of the participant Pure Research Model Act solely to collect generalizable data

7. Why the pure clinical model fails: Researchers seek to create generalizable knowledge, not to maximize the health of participants Research interventions are determined by protocol, not by characteristics of individual participants Example: Randomized Controlled Trials

8. What are researchers’ responsibilities to participants? Pure Clinical Model Act to maximize the health of the participant Pure Research Model Act solely to collect generalizable data X

9. Why the pure research model fails: The “pure research” model would imply that investigators are free to collect information from participants without any regard for their needs and interests. Implication for information of imminent heart attack? This is implausible.

10. What are researchers’ responsibilities to participants? Pure Clinical Model Act to maximize the health of the participant Pure Research Model Act solely to collect generalizable data X X

11. What are researchers’ responsibilities to participants? The “pure clinical” model fails, as does the “pure research” model. Where do we go from here?

12. Collaborative partnership Social value Scientific validity Fair subject selection Favorable risk/benefit ratio Independent review Informed consent Respect for participants 8 principles of ethical clinical research

13. What does “respect” require of investigators? Investigators should communicate individualized results to participants that are meaningful.

14. What constitutes meaningful information? Is the information likely to be clinically relevant? Are there implications for further screening, treatment or prevention? …relevant to reproductive decisions? E.g. Gene carrier status …relevant to life-planning? E.g. Early- or late-onset conditions without possible intervention …desired by participants for other cultural or social reasons? E.g. Information about ancestry

15. Respect and requests Respect for participants also confers a responsibility on investigators to respond to requests for results.

16. NIH Human Subjects Research Advisory Committee (1998) Participants may access research information unless: 1. Information would compromise a promise of confidentiality 2. Information may endanger the life or physical safety of an individual 3. Access would compromise the scientific validity of the study (e.g. blinding) OR 4. Information has not been established to have clinical utility or validity at the time of review

17. Participant access to information of uncertain significance Potential Concerns: Risk of misinformation Misinterpretation of information Cost of disclosure These concerns can and should be addressed, but they do not appear to be overriding reasons to withhold results.

18. Exceptions to disclosure  Information would compromise a promise of confidentiality  Information may endanger the life or physical safety of an individual  Access would compromise the scientific validity of the study (e.g. blinding) OR  Expected costs of access would make the study prohibitively expensive to conduct. If requested, study results should be disclosed to participants unless: *

19. Method of Disclosure Meaningful information should be disclosed in a manner that has meaning for participants. “Plain Language” requirements, etc. Disclosure to third-parties when necessary. Results should be offered. Similarly, when results are requested by participants, investigators should try to address the participants’ underlying concerns.

20. Investigators discover that two siblings have a gene preliminarily associated with a disease that may cause loss of visual acuity or blindness. If pathology is identified early, vision loss can be prevented. Should investigators inform the siblings of the findings? Does it depend on the type of study? Case #1 Revisited Yes—this result appears to be clinically meaningful Probably not—the information itself is enough to warrant disclosure

21. Case #2 Revisited Investigators are conducting a large epidemiological study to determine whether various factors (social, economic, genetic) are associated with a greater risk for the development of heart disease. Should the investigators notify participants of potential risk factors at the conclusion of the study? What if a participant requests his or her results? Investigators should disclose the results, but should ensure that the request is not based on a misunderstanding Probably not—these data are unlikely to be meaningful

22. Application What text should be included in protocols and consent forms?

23. Possible boilerplate text for informed consent The researchers will offer you the results of tests that they judge to be meaningful to you, including results that may be useful for your health care. If there is some information that you do NOT want to know about yourself, please tell us, or call Dr. _______ at ______. Also, if you would like the results of a specific test conducted during this study, please tell us, or call Dr. _______ at _______. (Grade level 9.3)

24. Conclusions Investigators have a responsibility to offer meaningful results to participants. I.e., information relevant to health, reproduction, life plans, culture or information specifically requested by participant Information should be communicated in a manner that is responsive to participants’ needs and interests Information is made understandable or disclosed to a third party Information is offered, not automatically disclosed Investigators should develop plans for dealing with results during study design, with the help of the IRB.