Noting that IRBs historically have “actively discouraged the disclosure of research results to individual participants,” a recently published consensus report1 calls for a paradigm shift toward transparency and disclosure of findings to research subjects.
“Our push toward more disclosure, we believe, is part and parcel of the larger cultural transition toward more engagement, collaboration, and transparency between investigators and research participants,” states the report by the National Academies of Sciences, Engineering, and Medicine.
This will not be done overnight, as the report calls for sweeping changes that include establishing a system to ensure accurate lab results are being reported to participants in studies and clinical trials.
In the interim, IRBs and researchers should start discussing ways individual results could be fed back to participants. If the Common Rule is finalized next year as currently proposed, the informed consent process would include information to participants about whether their individual results will be returned.
The report cites a “longstanding tension” in biomedical research between divulging or withholding results that may be poorly validated. Thus, investigators and IRBs often have asked research subjects to participate for the common good without expecting an individual breakdown of the findings.
“Investigators drop into communities or people’s lives, engage with them in often very personal ways, and then take off, never to be heard from again,” the report states. “Yet, people are curious about themselves, particularly about their health and their family’s health, leaving a sense of frustration and loss when investigators take but do not share.”
The rise of genetic research has driven this trend, as individual data heretofore unimagined is available to researchers. There have been longstanding exceptions to the general rule of nondisclosure, such as “duty to warn” if some important health concern is identified in a research subject. A more general argument is emerging that subjects should have access to their genetic data if they participate in such a study.
To gain more insight into this ambitious initiative, IRB Advisor talked to Jeffrey R. Botkin, MD, chairman of the National Academies panel and the associate vice president for research and professor of pediatrics at the University of Utah School of Medicine.
IRB Advisor: The report cites the need for a paradigm shift, which implies this is a beginning point that will take some time for full adoption.
Botkin: As the report emphasizes, we hope we’re going to see a gradual transition of more return of results over time. There are a variety of different pieces that will have to come together to make it more appropriate and more feasible. But right now, it is still possible in a lot of circumstances. Investigator sponsors certainly ought to be asking the question on a regular basis. Maybe, the answer is we are not ready yet, but I think it is appropriate to begin thinking in those terms.
IRB Advisor: Your report argues that full disclosure to human subjects will make research stronger.
Botkin: We think it is an opportunity to expand the relationships with research participants in a way we know participants appreciate. They often will want results and expect results even when investigators have advised they are not going to get them. It is something that is valued by people, and we think it is going to strengthen the relationship between investigators and participants, and that is going to have a lot of positive impact on the research process.
IRB Advisor: Favoring a case-by-case approach, the report recommends moving beyond firm rules (e.g., those in the Clinical Laboratory Improvement Amendments [CLIA]) that stipulate when results may be disclosed by clinical labs. However, noting that no such alternative exists for research labs, the report recommends that the NIH develop a “quality management system” for research labs.
Botkin: We are very sensitive to the concerns in this domain, which are that investigators are going to be returning results that are by their very nature uncertain because it’s research. The downside to returning results are that people may make important decisions based on information that proves to be wrong. One way to minimize that is to make sure that the laboratory quality standards are high. At this point, we’ve got CLIA, which is excellent for clinical laboratories and for some research laboratories. But it is not necessarily the right thing for all research laboratories. We think a better way to go would be to develop an independent quality standard system specially for research laboratories so that everybody can have a higher level of confidence in the results.
IRB Advisor: Have you had some pushback on this lab recommendation?
Botkin: One of the things in the report is to have the IRBs become more familiar and have access to expertise to help guide them on laboratory quality issues. We did a webinar last week, and one of the questioners sort of got the impression that we are asking the IRBs to judge the quality standards of laboratories in their institutions — to become sort of regulators of laboratory standards. That’s really not what we are looking for. We are looking for IRBs to become familiar with quality standards — to have that experience on the panel or available to the panel to provide input on quality issues related to a particular laboratory result. So, it is an expansion of responsibilities for the IRBs to have input and more knowledge and expertise in that laboratory quality domain.
IRB Advisor: Are you advocating that IRBs generally take a broader view of when individual results could be given to participants?
Botkin: Yes, very much so. I think that is a question that ought to be asked in the context of each project that comes to an IRB. Hopefully, folks have asked that question before it gets to the IRB. If you think results can be returned, then you ought to put that in your protocol and have the process and timing outlined there so the IRB can take a look at that. Conversely, if you don’t think it is appropriate to return results for whatever reason, then you should outline why you think that is the case, and the IRB can look at that as well.
IRB Advisor: You mention this question is now in the latest iteration of the Common Rule. If the default position is to inform participants, would the Common Rule or other regulations have to be changed?
Botkin: I don’t think we need regulatory changes at that level in order to accomplish this. I will say that the regulations don’t require anybody to return results, so it is not a matter of conforming with any regulatory requirements in that regard. In order to comply with regulations, IRBs don’t have to develop policies and procedures related to this issue. But we think it is advantageous and IRBs ought to play a role in this.
IRB Advisor: What about the old rationale that research subjects participate in studies to benefit future generations? Does this focus on individual results undermine that to some extent?
Botkin: I don’t think so because we see the return of results in some circumstances as something that is appreciated by participants. We don’t really see that as compensation, if you will, for the time, effort, and risks that people are willing to put into research. They are still contributing quite a bit out of their own goodwill. That situation won’t change even if you get some results back. So, it is not a contractual sort of thing. We still think it is important to maintain the altruism that is part of the people’s decision to participate in research.
1. Botkin JR, Mancher M, Busta ER, et al. Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. National Academies of Sciences, Engineering, and Medicine, 2018. Available at: https://bit.ly/2EbA9m9.