Harmonizing Return of Results Policies In International Psychiatric Genomics Research Collaborations

Abstract

BackgroundGenomic analysis by multinational collaborations is helping uncover the genetic architecture of psychiatric disorders. Reports from different countries have noted an emerging consensus that genomics researchers should, at a minimum, offer to return to participants clinically valid, medically important, and medically actionable findings generated in the course of research. However, countries often have different policies and means of regulating the return of results (RoR) to participants (e.g., laws; guidelines by professional organizations; judgments of ethics review boards). In terms of RoR policies, some recommend no return, others provide general guidelines about what to return, and many offer no guidance. Conflicting policies may generate situations where, within a study, some participants may benefit from the RoR and others not. Researchers could also decide not to do RoR to avoid conflicts with regulators in countries that restrict or prohibit it. We present an ethically-justified framework about which findings, if any, should be offered to participants in psychiatric genomics (PG) research. MethodsEthical and legal review of return of results practices, relevant guidelines, literature, and policies from countries that participate in international PG research collaborations was conducted to examine points of convergence and conflict. Iterative writing and revising of assessment reports with PG researchers and bioethicists was conducted to generate an ethically-justified framework regarding which genomic findings, if any, should be offered to individual participants. ResultsWe propose that 1) as has been advocated for genomic studies of other medical conditions PG researchers should, at a minimum, offer findings generated in the course of research that are clinically valid, medically important, and medically actionable. When resources allow, PG researchers should also offer non-medically actionable findings, that we argue are “clinically valuable” such as: 2) clinically valid findings that help corroborate or reject a psychiatric diagnosis; 3) clinically valid findings that provide information about important health risks; and 4) “likely clinically valuable” findings such as variants of unknown significance that are rare, missense or nonsense variants in genomic loci known to be associated with a psychiatric or other disorder that may help explain a participant’s symptoms. ConclusionsGenomic testing raises complex challenges for investigators, such as how to manage the increasing amount of clinically relevant findings (CRFs) emerging knowledge and novel technologies can generate. CRFs could impact participants’ health care by facilitating prevention, diagnosis, treatment selection, or a better understanding of the pathogenesis of a participant’s symptoms. Offering some CRFs could maximize the social utility of PG research by not only generating generalizable knowledge, but potentially directly benefiting those individuals who contribute to science by participating in these studies. We aim to spark a discussion about which CRFs should be offered considering the particularities of PG research and the potential risks and benefits to participants. Harmonizing RoR policies should help promote the benefits of responsible RoR.