Secondary variants and human subjects research

To the Editor: In the article titled “Return of Research Results from Genomic Biobanks: Cost Matters,” Bledsoe et al.¹ have performed a valuable service by outlining their concerns regarding the potential cost to biobanks of policies that favor the return of individual research results to clinical genomics research participants. They correctly characterize the ClinSeq study as one that has an ongoing, direct relationship with the participants and in which the return of results is practical. They contrast ClinSeq to biobank studies in which the data analysts have several degrees of separation from the participants and in which developing the infrastructure to return results could be complex and costly. Their plea is that the relationship of the research participant to the biobank and the costs of returning results are important factors to consider and that applying the ClinSeq model to all biobanks is impractical and could harm the larger research enterprise. These are important concerns, and research to quantify the cost of returning results in a range of research designs is sorely needed.

Yet Bledsoe et al.¹ seem to discourage any return of results in research involving biobanks, except when the biobank maintains the kind of direct involvement with participants that ClinSeq has. This may have the unintended consequence of incentivizing researchers to structure human genomics research studies as remote biobank-style studies to reduce costs and discourage direct engagement with research participants. I would argue that it is undesirable if this incentive were to be broadly realized, as our field needs to move toward more, not less, participant engagement. A reasonable question could be raised whether our field would benefit more from a larger number of less expensive, narrowly defined biobank studies with no participant engagement or a smaller number of more expensive studies with high degrees of ongoing participant participation, iterative phenotyping, and return of results.

I recognize that the law of unintended consequences operates at many levels in human subjects research—whenever we increase standards and human subjects protections, we incur increased costs and risk delays in discovery. Yet, recognizing what we owe back to research participants is a crucial part of ethical research. Bledsoe et al.¹ recognized the importance of returning some results, those that are analytically and clinically valid, confirmed in a Clinical Laboratory Improvement Amendments–certified lab, and have serious consequences for participants. We have to consider how best to identify medically important results and offer them back to participants in the range of research models we have, including those involving biobanks.

Our field cannot go to the extreme of returning nothing, whether a biobank is involved in a protocol or not. We need to move toward robust and ongoing participant engagement, for scientific reasons, out of respect for our participants, and to maintain the public support of the research enterprise. I propose to translational genomics researchers the following thought experiment: imagine yourself in a room full of the participants at the close of your study, and your assignment is to describe to them the kinds of medically useful data in your data set and then justify why you gave none of it back to them. I can’t do it.

Disclosure

The author is an uncompensated consultant to, and collaborates with scientists at, the Illumina Corporation as a part of his official duties.