IRB Chairs' Perspectives on Genotype-driven Research Recruitment

Laura M. Beskow, MPH, PhD; Emily E. Namey, MA; Patrick R. Miller, PhD; Daniel K. Nelson, MS; CIP, Alexandra Cooper, PhD

Disclosures

IRB. 2012;34(3):1-10. 

In This Article

Discussion

Identifying and contacting individuals about their interest in participating in research must take place within the context of well-established requirements for ethically responsible research.[12] Even so, research recruitment is typically considered less risky than research participation. When contacted by a researcher, individuals have a number of options, including not responding, expressing disinterest at the outset, or learning more about the research and then making an informed decision about whether to take part.[13]

Certain approaches to research recruitment, however, involve risks that can rise to the level of harm. Genotype-driven recruitment is one such approach, where potential harms associated with the use and disclosure of genetic information are linked to the offer to participate in research. At the same time, genotype-driven recruitment could significantly advance the pace of research on the functional significance of human genetic variation and speed progress toward the ultimate goal of benefitting human health.[14]

As a first step toward developing guidelines on ethical approaches to genotype-driven recruitment, we gathered empirical data from one stakeholder group, IRB chairs, about the acceptability of recontact for further research recruitment and the disclosure of individual genetic research results during the recruitment process. The distribution of responses we received to general questions on both of these topics was highly variable and seemed to suggest that the answer may often be "it depends." This conclusion is further reinforced by the statistically significant differences we found between responses to our general versus scenario-specific questions. A major consequence of these findings is that it is unlikely that there will be a "one-size-fits-all" solution, but rather several approaches to genotype-driven recruitment that may be ethically acceptable depending on a variety of context-dependent factors. Examples of such factors include whether the genotype-driven study focuses on the same medical condition as the study in which participants were originally enrolled, whether it involves the same researchers and/or institution, whether it involves the recruitment of family members, and how and by whom prospective participants are contacted.

Two context-dependent factors in particular generated strong agreement among our survey respondents: First, disclosures made during the informed consent process for the original study are key. Addressing the possibility of future research contact and disclosure of individual results during the consent process—and potentially offering participants choices about these—may help mitigate some of the ethical dilemmas involved in genotype-driven recruitment. Specifically, incorporating these topics into the original consent process is one way of addressing the considerations that IRB chairs selected in our survey as deserving more weight: avoiding unwelcome researcher contact and avoiding disclosure of unwanted genetic information. However, there are several ethical and logistical challenges involved in offering and honoring choices on consent forms,[15] and attention is also needed to developing appropriate and easy-to-understand consent language.

The second area of strong agreement that emerged concerned the importance of the clinical validity (and, to a slightly lesser degree, the clinical utility) of the information when deciding whether individual genetic results should be offered during the recruitment process. Issues surrounding the uncertainty and usefulness of genetic research results—together with ethical arguments based on respect for persons, beneficence, paternalism, reciprocity, and the boundaries between research and clinical practice[16] — fuel the continuing debate over the general issue of whether individual genetic research results should be disclosed to research participants.[17] Clinical utility has been the most frequently recommended standard,[18] but will likely be difficult to reach in the context of genotype-driven recruitment, where further research is needed specifically because more must be learned to decipher the meaning of genetic research results in terms of risk, inheritance, diagnosis, prognosis, and treatment.[19] When choosing the appropriate threshold for disclosure in genotype-driven recruitment, the counterbalancing concern about evasiveness when explaining why prospective participants are eligible must be addressed: If individuals are not offered their individual results, what should they be told about why they are being recontacted? No matter what approach is taken, researchers must be fully prepared to communicate and answer questions in clear lay language about what is known and not known about the role of genetics in their proposed area of research.

In this study, we collected data from a key stakeholder group to inform policy development on a rapidly emerging issue. Other studies of IRB professionals' views on issues arising in genomic research—such as what constitutes human subjects research, the need to obtain participants' further consent for new uses of biospecimens, the disclosure of individual genetic research results, and the risks associated with large-scale data sharing—have similarly reported a wide range of opinions.[20] This diversity of views may be due in part to a lack of federal regulatory guidance and established IRB policies on some of these new and unresolved questions.[21] To help address the ethical challenges in the swiftly evolving field of genomics, it may be especially important for IRBs to have access to a variety of resources, including input from scientific colleagues, individuals who can articulate the perspective of research participants, and experts in research ethics.[22]

Our national sampling frame and good response rate are important strengths of this work. Genotype-driven recruitment is a complex topic that we knew would be novel to most respondents, and we developed our survey instrument through multiple iterations and detailed cognitive interviews to help ensure that questions would be comprehended as intended and to identify answer options that should be revised or added. Several factors, however, may limit the interpretation of our results. First, we do not have data about the characteristics of IRB chairs who did not respond to our survey and thus cannot assess potential response bias; in general, the demographic characteristics of our respondents were similar to those found in surveys of IRBs on other topics.[23] Second, because our survey comprised primarily closed-ended questions and was completed online, we were unable to probe for even more nuanced views or to explore other factors that IRB chairs themselves might have identified as influencing their opinions. Third, to constrain the survey to a reasonable length, we did not include questions covering every possible issue (e.g., whether genetic research results are produced in a CLIA-certified laboratory, and the attendant implications for disclosure to participants).[24] Thus, further research among IRB leaders—perhaps involving semistructured interviews—is warranted. Input is also needed from other stakeholders—such as researchers, research participants, and treating physicians—for the development of sound recruitment policies that protect participants, yet avoid excessive restrictions that have a chilling effect on beneficial research.[25]

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