Although our data reflect the perspectives of our respondents and may not be generalizable to all IRB professionals, they offer important insights regarding the challenges that IRBs may face as they address return of results. First is the knowledge and expertise required to appropriately analyze these issues, especially in the context of a rapidly changing field where unprecedented amounts of genomic and phenotypic data are gained and shared at an extraordinary pace and the associations between these findings and disease development may change just as quickly. Second, although return of individual research results is not a new concept in clinical research—imaging studies have had a long history of revealing incidental findings that are communicated to research subjects34, 35
—return of results that have clinical relevance from basic science
studies, especially in genomic research, is a new concern. For some of our respondents, the interview process itself provided one of the first opportunities for in-depth analysis of this issue. Third, the increase in genomic studies that IRBs anticipate reviewing in the future creates even more tension regarding how to address the issue of returning research results. Finally and perhaps most important, is the lack of national guidance on this issue upon which IRB professionals can anchor their decisions. Neither the Common Rule nor current OHRP guidance address the issue of return of individual research results.1, 32
Many respondents in our study were not comfortable developing local policies in isolation. Even those IRBs who have some guidelines in place, including the requirement to validate research results in a CLIA approved lab before return, found that some real life situations precluded them from complying with their own rule.
However, despite these challenges and expressions of perplexity, respondents in our study were very thoughtful in trying to integrate all legitimate perspectives on this issue, and articulated many of the concerns previously described in the literature.1, 5, 9-20, 31
These concerns reflected several dimensions of and individual thresholds for uncertainty, including the broad scope of the science juxtaposed with the highly contextual nature of each ROR scenario, and the challenges of appropriately assessing the analytical and clinical validity and clinical utility of a particular research result. The concern of having an individual act on research results that may be incorrect or have low predictive power, or providing a research result that predicts a condition that has no medical intervention, fueled many of the uncertainties regarding how to appropriately assess potential risk and anticipated benefit. However, our respondents were firm in their position that a research participant’s right to know/ not know information about themselves be respected and they supported the return of validated, medically actionable results. These positions are similar to those reported by genetic researchers.22, 36
Two studies with genetic/genomic researchers, using survey and qualitative methods, respectively, both identified clinical utility, respect for participants, and minimizing harm to participants as the common reasons for determining whether to return results.36, 22
Participants in the qualitative study also considered the IRB to be a main authority to see out to ensure that rules were being adhered to before researchers took action. 22
However, as our study demonstrates, this can be a challenge when IRBs are still in the process of developing their own guidelines.
Only a few other studies have reported perspectives of IRBs on ROR.23,37
Lemke et al conducted a survey study with members of a professional group overseeing human subjects research where 78% agreed that an “ethical duty existed to return individual research results that could affect a participant’s health or health care.”23
This view was also supported by the respondents in our study, along with contextual variables, such as the type of disease in question and the strength of the association of the result with disease development or response to therapy. The contextual nature of the ROR scenario was further highlighted by Wolf et al. in a study where IRB chairs were presented with a scenario in which banked DNA was used in a research study to evaluate risk of Alzheimer’s disease.37
Nearly all IRB chairs in Wolf’s study expressed a desire to have predefined criteria regarding returning results.37
Although respondents in our study also wanted guidance on ROR, the type of guidance differed among the individuals, some wanted more concrete guidelines, others preferred ground rules or best practices to guide them.
We found that respondents often used similar terms in different ways or the same term to encompass a general concept without defining or clarifying what that term meant. The lack of a common nomenclature is a long standing problem in human subjects research, especially in human specimen research and biobanking.38
In our study, the frequent use of the terms validated
or clinical significance
without identifying the threshold for meeting those descriptions can hinder communication and decision-making between IRBs, researchers and research participants. Even in the research community, agreement is lacking regarding what these terms mean and how to measure them consistently.1
We also learned new perspectives. First, many of our respondents expressed a need to consider the meaning of a research result not only today, but also in the future. This concern was described especially when the researcher is maintaining contact with the research subject over time and is maintaining a registry or database of research results. The implication was that researchers may have a long-term responsibility to their research subjects to monitor the literature for the clinical relevance, validity and utility of stored research results and communicate relevant information to the research subjects in the future. In contrast to the NHLBI recommendations suggesting that researchers are only responsible for ROR for the length of time of the study,18
our respondents did not put a time limit on the responsibility for monitoring currently uncertain results for future relevance. Second, we learned that IRB professionals have a range of views regarding whether the IRBs should play an active role in decision-making about returning individual results. Some respondents felt that the IRB should oversee the decision-making process, but not necessarily be a decision-maker. Finally, although there was agreement that results should be returned to individuals who want them, there was little mention about how to incorporate research participant’s views or definitions on what conditions would constitute personal or clinical utility.
The most challenging tension for IRBs in regulating the return of individual research results, however, may be how the practice blurs the line between research and clinical care.35, 39
IRBs are responsible for the ethical conduct of research, not the ethical conduct of clinical care. Research is meant to benefit society, not the individual research subject. Yet, in our study, and in society today, “a special power was associated with genomic information.”40
Our respondents expected that genomic or genetic studies would provide important clinical information for the research participant. And therein lies the conflict. The expectation for individual benefit is antithetical to the traditional concept of research. Addressing the return of individual research results that may be acted upon by the research participant crosses the boundary between research and clinical care. However, in our study and others, the communication of information that may benefit the research subject may also be considered part of the IRBs moral obligation in their role to protect research subjects.23
It is not surprising that respondents expressed different views regarding the responsibility of the IRB to be actively involved in deciding whether a research result should be returned to an individual research subject. It is also not surprising that we lack national guidance.
Next steps: An IRB-researcher partnership
As IRBs are faced with real-life ROR situations, they will be forced to make decisions and develop management plans. Ground rules (and the range of acceptable interpretations) will need to be developed to address what conditions are either necessary or sufficient criteria for return (e.g., should actionable but unvalidated results be returned and what constitutes validity) and what situation trumps another. Although much effort is being devoted to the development of national and international policies for disclosing the results of genomic studies to research participants, there are opportunities at the local level to facilitate this process. One is the development of a partnership between IRB professionals and genomic researchers to approach the issue of return of results at their institution. Both IRB professionals and genomic researchers could benefit from a collaborative approach to addressing this issue, with each providing the necessary context and details to inform local management plans. Most importantly, research participants and the local community could also benefit from this partnership. The partnership could help assess local needs and develop management plans to meet those needs (). Training exercises involving contextually-based case scenarios could be developed to provide IRBs and researchers with practice in collectively conducting risk/benefit analyses, and opportunities to understand each other’s concerns in addressing this issue. Similarly, such exercises could provide opportunities to develop a common nomenclature of relevant terms and examine the logistics, infrastructure and resources needed to support ROR. The partnership could lead to the development of a management plan that incorporates ways to address mutual concerns. In addition, the naturally occurring experiments that IRBs conduct in their research oversight responsibilities could be studied and analyzed, evaluating factors influencing development of different ROR policies and procedures. Having IRB professionals and researchers working together to address return of results at the local level can also inform development of policy at the national level.
IRB -Researcher Partnership to Address Return of Individual Genomic Results (ROR)