A team from Columbia University is carrying out a set of interviews and surveys they intend to use to create guidelines for acquiring informed consent from subjects of genomic sequencing studies for the return of "incidental," or secondary, findings.
The effort, led by Paul Appelbaum, director of the division of law, ethics, and psychiatry at Columbia, began last September as one of seven projects awarded a total of $5.7 million by the National Human Genomic Research Institute aimed at creating policy guidelines on how and when to disclose genomic information to the subjects of research studies.
Appelbaum's study, which received a total of $400,000 from NHGRI, is using feedback from genomic researchers and subjects of sequencing studies at Columbia to create a set of recommendations for obtaining informed consent for the return of so-called "incidental" findings to subjects of genome sequencing research.
Such information, which is not related to the central aim of a given study, has presented an ethical quandary for researchers since it may be highly relevant to the health of participants or their relatives but is not covered by current consenting practices. While there is no consensus on the best framework for providing such results to research participants, a survey published earlier this year in Genetics in Medicine indicates that physicians believe these findings should be returned to adult patients that receive sequencing-based tests in a clinical setting and when medical intervention is possible, though there was a lack of agreement on other circumstances (CSN 3/21/12).
Acknowledging the complexity of the issue, Appelbaum told Clinical Sequencing News that the team may not arrive at an "exclusive" set of recommendations. "We're not sure at this point that there's one right answer, or just one way to go through this consent process."
It's likely, he said, that the group's recommendation "will include options, and we'll indicate the plusses and minuses of each of the options."
Appelbaum said his group has so far completed the first step toward creating these guidelines: a review of the scientific literature on the return of secondary findings in genetic and genomic research, which they have used to create questions for a set of interviews of both researchers and subjects, as well as a more detailed survey that will be the final section of the project.
The group has already conducted its interviews with genomic researchers, Appelbaum said, and is just about to start interviewing genomic research subjects. In all, the interview portion of the study will involve 30 researchers and 20 subjects.
Appelbaum said the pool of research subjects will be drawn from genomic sequencing studies related to congenital heart disease, breast cancer, and other disorders that have been conducted at Columbia under the direction of Wendy Chung, who is also leading her own project under the NHGRI program.
He said most of these will have had whole-exome sequencing, but did not provide examples of specific studies from which they will be drawn. "They seem to us to be a good group to query because for them, although the questions are hypothetical in the sense that nobody is offering them this data right now, they’re not quite hypothetical given that there’s a possibility at some point in the future they may be offered some of their data," he explained.
Appelbaum also declined to detail any of the 30 investigators who have been interviewed, but he said the team's interview questions are intended to assess their thoughts on the scope of informed consent guidelines for returning sequencing data.
Questions for the subject group will largely parallel those asked of the investigators, namely "if the possibility existed of getting some of their genomic data back, what would they want to know in order to make that decision?" Appelbaum said.
Within these main questions, the interviews will also deal with subcategories the team pulled from the literature review. For example, Appelbaum said, questions will deal with a variety of risk information that could or could not be included in the informed consent process.
The larger category of "risk" includes all sorts of issues, he said, including confidentiality risks, risks of false positive or false negative results, risk of discrimination based on genomic data, risks of anxiety or depression, as well as the impact the information might have on a subject's family: interpersonal risk.
"The range of issues one could disclose just in that one category of risks is fairly broad," Appelbaum said. "And one could go into considerable depth on any of those. Yet if one discloses everything one ends up with an overwhelming and unmanageable process, so some choices have to be made somewhere along the way."
Once the interviews are completed, Appelbaum's team will then conduct a survey of about 200 genomic investigators, which they plan to begin within the next month. The survey will mirror the questions asked in the researcher interviews, he said, but will go into more detail.
Appelbaum said he hopes the final recommendations will resolve the tension between a desire to provide sufficient information for subjects to make a "meaningful choice," and the need to limit the consent process to a "manageable" amount of information.
"The [consent process] has the potential to take a great deal of time and effort," Appelbaum said. "That's something neither investigators nor subjects seem to think is desirable."
"So somewhere in the middle, maybe at multiple points, there [need to be] compromises that can be made between the desire to be comprehensive and the reality that one needs to have a consent process such that subjects can actually absorb the information," he said.
According to Appelbaum, the team is also asking about issues of returning results to parents of children as well as several other categories of what he called "special" subjects, such as patients who may no longer be, or have never been, competent to make decisions, or subjects who have died but whose genomic information might have significance for their family members.
"Management of that is something that almost hasn't been written about at all," Appelbaum said.