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Committee Members Suggest Guidelines for Returning Sequencing Results to Research Participants

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NEW YORK (GenomeWeb) – Members of the Return of Results committees of the Clinical Sequencing Exploratory Research (CSER) Consortium, the Electronic Medical Records and Genomics Network (eMERGE), and the eMERGE Consent, Education, Regulation, and Consultation working group have devised recommendations intended to help researchers navigate the thorny issue of whether and how to return next-generation sequencing results to research participants.

The guidelines, published this month in the American Journal of Human Genetics, aim to provide some clarity for researchers performing next-gen sequencing studies who discover genomic information that could impact their subjects' health.

Last year and in a subsequent clarification this year, the American College of Medical Genetics and Genomics devised recommendations for returning incidental findings from next-generation sequencing performed in a clinical context. The ACMG came up with a minimum gene list, and recommended that laboratories performing clinical exome or whole-genome sequencing should also provide results about those 56 genes since mutations in them would have direct relevance to a patient's health.

Senior author Gail Jarvik, who heads the division of medical genetics at the University of Washington, told Clinical Sequencing News that the ACMG guidelines prompted discussion about whether similar recommendations should be made for research volunteers.

The guidelines published in AJHG differ from those the ACMG developed for clinical sequencing purposes, in that the committee members do not suggest that researchers should specifically seek out medically actionable information from participants' genomic data.

One principle guiding the group, Jarvik said, is that the "primary goal of research is to gain scientific knowledge, not patient care." The committee "felt strongly that researchers do not have a duty to hunt through a participant's genome for anything that might be important."

However, if a research study is designed specifically to evaluate medically actionable genes or if a researcher happens upon an actionable finding, those results should be returned to consenting individuals, she said.

Actively hunting through genomic data for medically relevant information involves diverting both time and resources away from the primary research question, Jarvik added, and should not be the goal of a basic scientist. In addition, such researchers may lack the ability of clinical genomicists to interpret such information and should not be expected to search for genomic findings related to diseases outside of their area of expertise.

Another key principle that guided the committee, said Jarvik, was the belief that the participant should have a choice about whether or not to receive genomic information. If a study is designed in such a way that returning results is a necessary part of the study, that should be communicated clearly and individuals not wanting results should not enroll in the study, Jarvik said.

Returning genomic information about children has long been an area of controversy, and Jarvik said she did not expect that the committee would reach consensus about whether and when to return genomic data on children.

Historically, children are not offered clinical testing for adult-onset disorders in order to preserve their right to make that decision for themselves when they reach adulthood. However, the committee wrote that "the case of an incidental finding discovered in sequencing DNA from a child with no prior warning of that variant in the family is different from the past clinical case of the known existence of the genetic finding in one or more other family members."

As such, the committee concluded that during the consent process, parents should be offered the choice of having adult-onset actionable incidental findings returned, along with counseling. The committee however, offered one caveat. In cases where one or both parents are already known to carry variants related to adult-onset conditions that do not change clinical management in childhood, the discovery of the same variant in the child does not need to be returned since the family already is already aware of its presence.

Moving forward, Jarvik said that one area she expected would remain controversial is whether results must be confirmed in a CLIA environment before being returned.

The authors agreed that while prospective studies that plan to return sequencing results should include plans to confirm those results in a CLIA-compliant laboratory, "actionable information might be learned from assays that cannot be easily confirmed in a CLIA-compliant laboratory."

Researchers have already run into this issue. At the Personal Genomes meeting at Cold Spring Harbor Laboratory several years ago, Gholson Lyon, a psychiatrist at the University of Utah, discussed a research case where he had compelling genetic information discovered through next-generation sequencing but there was not a CLIA-compliant test through which to deliver such information back to the participant that wanted the results.

However, Jarvik said that many people, including herself, do not interpret the CLIA law in such strict terms and said that as a clinical geneticist, she would rather have researchers bring her non-CLIA results and then she could do a clinical test in a clinical setting and provide care for that patient. However, she said, "many researchers have been afraid to use that model because of the thought that non-CLIA results are problematic."

Another issue that remains unsettled is the best way to deliver results, Jarvik said. "There are a lot of open questions about best practices," she said. "We need to understand how people process actionable genome information." In addition, there should be research on how to deliver results in such a way that it is ethical and doesn't waste resources.

The recommendations published in the AJHG are not required, Jarvik said, nor are they likely to be the final say. However, she said, the hope is that they will provide guidance both for researchers and for institutional review boards that decide whether or not to approve such research studies on what is the consensus on returning genomic information to research participants.

The hope is that the guidelines will "set a tone that the expectation in the future is that if you find something of medical importance to a participant, you should share that information with them," Jarvik said.

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