'Reevaluating the “right not to know” in genomics research' by Nina B.Gold and Robert C.Green in (2022) 24(2) Genetics in Medicine 289-292 comments
In clinical exome or genome sequencing, the American College of Medical Genetics and Genomics (ACMG) has recommended that a minimum set of secondary findings for actionable conditions should always be offered to patients. In the research domain, millions of individuals have been sequenced, but the return of actionable genomic results is rarely offered. In most research projects that do offer the return of genomic information, participants are asked at the outset whether they wish to be contacted with genomic results of medical importance in a consent process that often stresses potential harms, such as privacy threats or psychological distress, over potential benefits. If participants answer “no,” they are rarely asked again or offered the opportunity to change their response. Participants who decline the return of genomic information about themselves in research are said to be asserting their autonomy around the “right not to know.” The recent report by Schupmann et al challenges this paradigm by showing that participants’ decisions about receiving unanticipated genomic information in research may change when they are given more information and an opportunity to reconsider. These findings prompt us to ask if we can expand autonomy by offering participants opportunities to change their choices, given new experiences in their lives or advances in medical science. Furthermore, should we more fundamentally reappraise the “right not to know” in research by routinely alerting participants to a specific finding within their own DNA and only then allowing them to decide how to proceed?
Although there is no accepted standard for the variants or genes to be returned in genomic research studies, many investigators return pathogenic and likely pathogenic variants in the genes on the ACMG list of secondary findings described earlier. Even within this limited list, the type of disorder, penetrance and expressivity, and available treatments and surveillance protocols can vary widely. Some research participants who decline genetic information may not fully understand how such information might impact their lives. A man with syncopal episodes might not appreciate that a variant associated with arrhythmogenic right ventricular cardiomyopathy could provide an explanation for his symptoms and a course of action to address them. A woman with a family history of breast cancer might not recognize the scope of surveillance protocols available to BRCA1-positive individuals, wrongly assuming that her only option in the case of a positive finding would be mastectomy. In these cases, prioritizing the right not to know with a single global question about returning genomic findings could preclude the disclosure of life-saving information. We rarely ask what happens to people who could have learned about medically actionable genomic information but declined results.
The report by Schupmann et al begins to address this question. The authors contacted more than 150 participants in a genomic research study who initially declined genetic results (“refusers”) and a cohort of individuals who had accepted them (acceptors). The researchers then provided participants with an educational intervention and asked if they would reconsider their original decision about receiving genetic findings. Importantly, roughly half of participants who had originally declined the return of results changed their decision (“reversible refusers”). Three-quarters of the reversible refusers believed that they had initially chosen to receive genetic results. The proportion of “persistent refusers,” those who were steadfast in their decision not to learn secondary genetic findings, was found to be less than 1% of the initial study population. The finding that a high percentage of refusers reconsidered their decision (and incorrectly recalled their initial choice) requires us to rethink how we ask about the return of genetic information in research. Should we take no for an answer, or at least for a permanent answer, when research participants initially decline actionable genetic results?
In considering this issue, we address 3 separate but interrelated questions.
Those questions are
- Should Actionable Genetic Results Routinely Be Offered for Return in Genomic Research Studies?
- Should Research Participants Be Offered Genomic Information More Than Once?
- Can Autonomy Be Enriched by an Incremental Disclosure and Choice Process?
