From the Director: Taking a look at the National Academies’ report on returning individual research results to participants

Elisa Hurley

In July of this year, the National Academies of Science, Medicine, and Engineering (NASEM) released a report titled, “Returning Individual Research Results to Participants: Guidance for a New Research Paradigm.” It’s a comprehensive report that raises many important considerations and proposes a number of thoughtful recommendations on this very timely topic. I won’t be able to do justice to all of its details and nuance here. Instead, I’ll share what I take to be some key themes and takeaways, including for IRBs.

Broad Overview

At the broadest level, the report promotes the return of individual research results. The authors suggest that greater attention to the return of individual results is part and parcel of larger trends in the research enterprise around patient and community engagement. One of the committee’s guiding principles is that research “participants bring essential and valuable information to the research enterprise, and as a matter of reciprocity, respect, transparency, and trust, return of results should be routinely considered in the design of research protocols” (2-20).  But, the report also acknowledges that returning results is complex and resource-intensive; while there are very often compelling reasons to return results, these reasons need to be balanced against the risks and burdens of return—for both individuals and for society generally. The report also acknowledges that, while a consensus is emerging that return of results should be routinely considered as part of the research process, the creation of best practices and guidance for when and how to return results is lagging far behind. The report aims to prepare sponsors, investigators, institutions, and IRBs to align their practices around return of research results with widely held principles.

Scope and Structure

Before I delve further into some themes of the report, let me say a bit more about its scope, and structure. The report focuses on return of individual research results generated from laboratory tests of human biospecimens where that goes beyond genetic tests to include, for example, tests of tumors to identify cancer biomarkers and epidemiological studies using specimens to determine environmental exposure to toxins. It does not include return of results from imaging, behavioral, or cognitive tests. The report considers return of both anticipated and unanticipated results that are related to the primary objectives of a study, but is not concerned with incidental findings—that is, findings that are unrelated to the aims of a study.

Across its six main chapters, the report puts forward 12 specific recommendations, directed at a range of stakeholders, including institutions, sponsors, IRBs, regulators, and research participants. The recommendations are “designed to help (1) support decision making regarding the return of results on a study-by-study basis, (2) promote high-quality individual research results, (3) foster participant understanding of individual research results, and (4) revise and harmonize current regulations” (xxi).

Takeaways for IRBs

The NASEM report has a number of implications for IRBs. First and foremost, IRBs are identified as central stakeholders in the process of promoting and facilitating return of research results. The report recommends that IRBs require plans for return of results be included in investigators’ protocol submissions. But, the report also suggests that the IRB’s role should go beyond reviewing such plans to ensure they reflect an appropriate decision-making process. The IRB should also evaluate return of results plans and determine whether they are ethically appropriate.

The report extends this role to evaluating laboratory quality. As I will mention in the key themes below, the report recommends that, until their proposed quality-management system for research laboratories is created, and assuming changes to the current CLIA regulations, the IRB should be responsible for assessing whether the quality of research results generated in a non-CLIA lab is sufficient for the results to be returned. The report acknowledges that IRBs may currently be ill-equipped and unprepared for this role, given a lack of first-hand experience with return of results, scientific and laboratory expertise, existing policies and procedures, and an existing evidence base for good practices. Taking on this responsibility will require significant training and consultation with scientific experts, laboratory quality specialists, patient advocates, and communication experts, amongst others; the report acknowledges, these kinds of changes will not happen overnight.

Key Themes and Highlights

Below are what I see as a few key themes and highlights from the report:

  • Focus on process and decision making. Rather than recommending specific conditions under which results should be returned or should not be returned (for instance, all results that reach a certain threshold of clinical utility should be returned), the NASEM report’s recommendations instead focus on the process by which study-specific decisions about whether to return results should be made, and, specifically, on the sorts of considerations that should guide such decisions. According to the report, what’s important is that in each individual case, a thoughtful process is undertaken to determine whether to return results, which results to return, and how best to return them.

    This is, to my mind, the richest part of the report, and, again, I can only skim the surface here. Briefly, the types of considerations the report identifies and then comprehensively examines are: (1) the validity and quality of the results, (2) the value of the results to the participants, and (3) the feasibility of returning the results. With respect to consideration (2) specifically, the authors make the point that, in a departure from other consensus statements on return of results, they have “chosen to de-emphasize the respective influences of clinical and personal utility in decisions regarding the return of individual research results by focusing more inclusively on results that have value to participants” ((4-4), emphasis added). This requires that investigators not make assumptions about the kinds of results that participants might (or should) want, and instead think about value from the perspective of the participant—that is, what would be meaningful to them, given their perspective on the risks and benefits, their understanding of the tradeoffs, and a variety of other contextual factors that the committee examines in more detail.

    According to the report, investigators should ascertain and incorporate the needs, values, and preferences of participants into their decision making regarding return of results. To foster this process, the committee recommends consulting with community advisory boards and engaging participant groups or advocacy organizations throughout the research design process. The report acknowledges that—at least until a robust evidence base regarding the values of various results for various stakeholder communities is created—the process of determining value for participants will be time- and resource-intensive.

  • Emphasis on quality of communication of results. The longest chapter in the report, Chapter 5, explores how to effectively and appropriately return research results. Again, the emphasis is on tailoring the process of offering and returning results to the preferences, needs, backgrounds, and resources of the research participant; the chapter offers a number of concrete strategies and examples for how to do this given variability in science and health literacy and other contextual factors.

    The chapter makes clear that good return of results practices involve not just determining what kind of information to return (e.g., should information with unknown clinical significance be returned?), but also facilitating understanding of the meaning, use, and limitations of the results by, respectively: providing appropriate reference information for results; identifying key take-aways about actionability (or lack thereof) for a particular result; and communicating uncertainties and qualifiers about the information provided.

    Identifying appropriate methods for communication—for instance, in person, by mail, or using an electronic patient portal—and appropriate visualizations, is also part of the process. The modalities should be matched to participants’ needs and the context of the research results. Here, too, the report emphasizes the importance of community input into dissemination and communication plans and suggests looking to general principles about effective communication in other domains, such as clinical care.

  • Need for incentives and the role of funders. The report points out that one of the barriers to instituting routine practices of returning individual research results is lack of incentives to do so. We may all agree it’s a good idea and the right thing to do, but there is no regulatory requirement to plan for the return of research results (though it’s worth noting that the revised Common Rule requires that, when relevant, a statement about whether research results will be returned, and in what circumstances, must be included in consent forms). The field therefore needs incentives to encourage and support planning for return of results as a routine part of the research process. The report recommends that research sponsors and funding bodies require explicit return-of-results plans in funding applications.
  • Changing the regulatory environment. One of the report’s key points is that the current regulatory environment does not adequately support the return of research results. The authors highlight, for instance, the well-known conflict between CLIA and HIPAA regulations, whereby CLIA requires that any lab performing tests on human biospecimens for the purposes of returning health information to an individual patient be CLIA-certified (which many research labs are not); meanwhile HIPAA’s Privacy Rule allows people to request access to their protected health information whether or not the result is generated in a CLIA-certified lab. The report makes specific recommendations to remove this conflict and harmonize the HIPAA rules and the CLIA regulations. It also suggests harmonization among NIH, FDA, OHRP, and HIPAA, which currently use different terminology around private health information and identifiability, and do not consistently support the interests of participants in receiving their individual research results.
  • The importance of laboratory quality. The report recommends the creation of a quality-management system for research laboratories that could serve as an alternative to CLIA-certification, for circumstances in which research results are not intended to be used in clinical decision making and CLIA certification seems unnecessary to ensure that research results are of sufficient quality to be returned (S-11). Until such a system is developed, or in cases where valuable results were generated but were unanticipated by the investigator, the report recommends that IRBs, as part of their review of whether a return of results plan is appropriate, determine “that the quality of the laboratory analysis is sufficient to provide confidence in the result to be returned” (3-22).
  • Developing a learning system for return of research results. Throughout, the report acknowledges that since the return of research results is a relatively new process and there is no current evidence base for determining best practices, the research community needs to develop a “learning system in which processes for returning research results are continuously evaluated for benefits and harms in order to support the best practices over time” (5-34). Building an evidence base will take time and resources; the report recommends that research funders sponsor empirical research on return of results practices.

Overall Conclusion

Overall, the NASEM report is an important addition to the current conversation about return of research results, and provides further support for the idea that we are currently in the midst of a significant paradigm shift regarding research participants’ access to their research results. The report, like the recent work of the Multi-Regional Clinical Trials (MRCT) Center of Brigham and Women’s Hospital and Harvard in this area, continues to move the conversation beyond general principles and provides concrete, detailed strategies for changing practices around return of results on the ground. The NASEM report acknowledges that the recommendation will create new demands on all of the stakeholders in the research enterprise, and that changing practice as significantly as they are proposing will take time.

There is no question the report’s recommendations constitute a tall order for the research enterprise, one that would involve significant investments of resources on all fronts. Can we envision a research enterprise in which institutions, regulators, sponsors, and IRBs are all willing and able to make that investment?  What will it take to get us there? Who needs to lead the way? I welcome your thoughts about whether the report’s recommendations should be read as aspirational, or whether you think we, as a community, can  implement these changes.

Opportunity for Further Exploration

There is a lot more, of course, to explore regarding this report and its implications for IRBs, and, fortunately, we have an opportunity to hear straight from two of its authors. I hope you will join us for our October 3 webinar, Return of Individual Research Results: the NASEM Report and the Role of the IRB. Presented by Jeffrey Botkin, MD, MPH, and Amy McGuire, JD, PhD, two members of the NASEM committee, this webinar will summarize the report’s overall recommendations and will identify some IRB strategies for returning individual research results. To learn more and to register, visit PRIM&R’s website.