Genotype-driven recruitment is an emerging approach to genomic research that poses ethical challenges stemming from the use and possible disclosure of genetic research results as part of the offer to participate in additional research. The concerns are exacerbated by the uncertain nature of most genetic results: further research is needed specifically because more must be learned to understand their meaning in terms of risk, inheritance, diagnosis, prognosis, and treatment (Beskow et al., 2010
). Genotype-driven recruitment will become an increasingly important tool as scientists seek to better understand the function of the human genome by recruiting individuals already known to have particular variants for in-depth phenotyping.
To begin informing the development of policies that both protect participants and facilitate beneficial research, we conducted in-depth interviews with participants in genomic research where genotype-driven recontact occurred. Our interviewees were drawn from six studies that differed in terms of basic study design and study population, thus offering the opportunity to glean a rich array of perspectives.
Given this diversity, it is particularly striking how consistent our interviewees’ responses were to certain questions— both within and between studies. Nearly all responded favorably to the general acceptability of recontact for the purposes of research recruitment. These responses were commonly accompanied by statements of altruism and a positive attitude toward research in general—perhaps reflective of the attitudes that might be expected among many of those who would be candidates for genotype-driven recruitment, i.e., people who have already agreed to participate in at least one research study. Genotype-driven recruitment was viewed especially positively as a sign of scientific advancement and an opportunity to take part in a promising area of research. A substantial majority of our interviewees were amenable to contact about studies conducted by researchers other than those who conducted the original study, perhaps again reflecting support for and trust in the research enterprise among those who have already agreed to participate in research. Across all studies, there was significant interest in receiving information about aggregate research results, oftentimes for reasons related to reciprocity and staying updated on research progress.
For several of our key questions, however, interviewees’ responses varied both within and between studies. Although many deemed it important to be informed up front whenever possible about the potential for future research contact and to have a choice about such contact, others felt that having a choice about actually participating in future research was sufficient. Similarly, many were amenable to taking part in research on other medical conditions, but others expressed a preference to help with research on conditions affecting them or their family and friends. Factors related to study design and study population could help explain these findings. For example, participants in studies that are otherwise perceived as one-time, circumscribed events (e.g., Epilepsy) may assign more importance to being notified about the possibility for future contact as compared to studies where the ongoing nature is an integral aspect (e.g., Biobank). Populations that are frequently recruited for research (e.g., CF patients) may assign less importance to being notified about possible recontact if they are already accustomed to being approached frequently. Such populations may, however, feel less able to also contribute time and energy to research on conditions other than their own. Study populations defined by having multiple affected family members (e.g., Autism-AGRE) may feel similarly constrained with regard to research on other conditions, and also rate advance notice about future research contact more highly.
Reactions to our questions about the disclosure of individual genetic research results in particular tended to vary within and/or between studies. Common themes across all of these questions included explaining the purpose of recontact, informing decisions about participation in further research, reciprocity, “information is valuable,” and the possibility of medical or personal benefit, as well as competing concerns about undue worry, distress, misunderstanding, and confusion. Specifically with regard to our general question about whether researchers should disclose individual results from the first study during the recruitment process for further research, the majority of interviewees in five of the studies said “yes”, but those in the sixth study—the Environmental Polymorphisms Registry, a population-based biobank of healthy volunteers—had more reservations. This finding points to a potentially significant explanatory factor, which is that patients
, i.e., people who have been diagnosed with the condition under study or parents of children with the condition, may likely perceive the risks and benefits of receiving individual genetic results very differently than those who have not been diagnosed with the condition (Cadigan et al., 2011
; Namey & Beskow, 2011
; Tabor et al., 2011
Responses were more mixed and less favorable to our question about disclosure of research results that lacked clinical validity. Although many of our interviewees were receptive to uncertain information as long as the uncertainty was clearly explained, our results suggest that not all people diagnosed with the condition under study will find net benefit in information that is ambiguous with regard to informing their understanding of their illness. Likewise, healthy volunteers recruited as controls are unlikely to view unsubstantiated information about a condition they do not have as beneficial, particularly if there is uncertainty about the meaning of the information for their future risk of that condition. Overall, our interviewees seemed generally less concerned about individual results lacking clinical utility, often based on the expectation that such results would still provide information or answers about their illness (for people diagnosed with the condition), or the expectation that there could still be personal utility as well as hope for future interventions (both for people with and without the condition). Indeed, a potentially concerning facet of our findings is the extent to which our interviewees assumed that genetic research results would convey information serious and certain enough that they would base reproductive or life-planning decisions on it.
As noted in the Methods section, the interpretation of all of our findings is subject to a number of limitations. Within the time and resource constraints of our research, we were only able to interview a small number of participants in each of the original studies and these were not randomly sampled. In addition, most of our interviewees were white and many were highly educated, characteristics that followed from the composition of the original studies from which they were recruited. It is therefore critical to note that our findings cannot be considered generalizable. We described the approximate proportions of interviewees who gave different responses in order to facilitate the clear communication of our data across multiple dimensions, but these proportions apply only to our particular study sample.
Notwithstanding these limitations, our findings represent what we believe are the first data from research participants about genotype-driven recruitment. We carried out in-depth interviews and thus were able to gather important and nuanced insights into participants’ range of experiences and opinions, providing a strong foundation for future research.