Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?

Abstract

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise.

Keywords:

• genetics (clinical)
• genetic research
• human subjects research
• research ethics

Acknowledgments

This article is not subject to US Copyright Law.

The authors would like to thank Ben Solomon, Sara Hull, Karen Rothenberg, Justin Lowenthal, and all of our colleagues in the NIH Department of Bioethics for their thoughtful advice and careful reviews throughout this project. The opinions expressed in this article are those of the authors. No statement in this article should be construed as an official position of the National Human Genome Research Institute, National Institutes of Health, or Department of Health and Human Services. This research was supported by the Intramural Research Program of NHGRI, NIH.

Notes

For convenience we use “genome” and “genomic” throughout the article, although in many cases “exome” or “exomic” would also apply.

There has also been considerable debate about the proper role of informed consent in the disclosure of genetic incidental findings. An obligation to look for and disclose incidental findings, as discussed here, rests on the assumption that participants have agreed to receive these findings.

If one accepts our argument that an obligation to look could exist, it remains open whether investigators could, through robust and transparent informed consent, waive such an obligation. While reasonable minds could disagree, we do not believe that simply informing subjects of an intention not to look is sufficient to defeat an investigator's prima facie obligation to look. As our analysis will make clear, however, we believe a determination that an obligation to look exists may be modulated by special characteristics of an individual study.  For example, if researchers can convincingly make a case that this obligation would pose an undue burden on their specific research, then our analytic framework would suggest that it is inappropriate to impose an obligation to look in that case.

This tension is apparent in one of Richardson and Belsky's examples, in which providing participants in a malaria study with treatment for schistosomiasis would enhance the health of the participants, but the resources required might mean the malaria study itself is impeded or delayed (Richardson and Belsky 2004).

Other bioethicists have largely accepted Richardson and Belsky's views, with a few minor adjustments. Joffe and Miller argue that the responsibilities of researchers flow only from the ethical obligations of science and research, not those of primary care (Joffe and Miller 2008; see also Litton and Miller 2005). Still, the practical implications of their arguments are aligned. Resnik (2009) holds that ancillary care obligations are variable depending on the context of the study, but in certain cases can be quite broad. Dickert and colleagues (2007) seek to expand even further the obligation to provide ancillary care, suggesting that when the researcher has the ability to help, when the participant is especially vulnerable, and/or when there is a strong level of engagement between the researcher and participant, this obligation may be strengthened.

F. G. Miller and colleagues (2008), however, do not believe the ethical obligations of the investigator–subject relationship include any affirmative duty to seek out incidental findings.

It is worth noting that some commentators have argued that disclosing incidental findings could plausibly be construed as a risk or harm to participants, rather than a benefit (see, e.g., Parker 2008). For example, disclosing incidental findings could cause anxiety or depression, require the participant to have expensive and invasive follow-up tests, and/or lead the participant to take prophylactic steps such as mastectomy that are both painful and costly. These potential risks are well worth considering, but within the scope of this article we focus on the benefits possible from seeking and disclosing incidental findings.

23andMe, one of the leading direct-to-consumer genetic sequencing firms, is currently piloting a whole-exome sequencing service. See 23andMe (2012b).

Specifically, nonsynonymous, stop, frameshift, and splice mutations.

Right now, many scientific researchers may lack expertise and thus find it difficult to adequately analyze genomic sequence data and identify incidental findings with clinical significance. This will likely change, however, as genomic sequencing technologies and analytic tools continue to improve. In the meantime, the extra effort required of nonexperts can be considered as part of the burden of analysis.