Stakeholder views on secondary findings in whole-genome and whole-exome sequencing:a systematic review of quantitative and qualitative studies

Purpose: As whole-exome and whole-genome sequencing (WES/WGS) move into routine clinical practice, it is timely to review data that might inform the debate around secondary findings (SF) and the development of policies that maximize participant benefit. Methods: We systematically searched for qualitative and quantitative studies that explored stakeholder views on SF in WES/WGS. Framework analysis was undertaken to identify major themes. Results: 44 articles reporting the views of 11,566 stakeholders were included. Stakeholders were broadly supportive of returning ‘actionable’ findings, but definitions of actionability varied. Stakeholder views on SF disclosure exist along a spectrum: potential WES/WGS recipients’ views were largely influenced by a sense of rights, while views of genomics professionals were informed by a sense of professional responsibility. Experience of genetic illness and testing resulted in greater caution about SF, suggesting that truly informed decisions require an understanding of the implications and limitations of WES/WGS and possible findings. Conclusion: This review suggests that bidirectional interaction during consent might best facilitate informed decision-making about SF, and that dynamic forms of consent, allowing for changing preferences, should be considered. Research exploring views from wider perspectives and from recipients who have received SF is critical if evidence-based policies are to be achieved.</p

Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research

Genome-wide sequencing in a research setting has the potential to reveal health-related information of personal or clinical utility for the study participant. There is increasing pressure to return research findings to participants that may not be related to the project aims, particularly when these could be used to prevent disease. Such secondary, unsolicited or 'incidental findings' (IFs) may be discovered unintentionally when interpreting sequence data, or as the result of a deliberate opportunistic screen. This cross-sectional, web-based survey investigated attitudes of 6944 individuals from 75 countries towards returning IFs from genome research. Participants included four relevant stakeholder groups: 4961 members of the public, 533 genetic health professionals, 843 non-genetic health professionals and 607 genomic researchers who were invited via traditional media, social media and professional e-mail list-serve. Treatability and perceived utility of incidental results were deemed important with 98% of stakeholders personally interested in learning about preventable life-threatening conditions. Although there was a generic interest in receiving genomic information, stakeholders did not expect researchers to opportunistically screen for IFs in a research setting. On many items, genetic health professionals had significantly more conservative views compared with other stakeholders. This finding demonstrates a disconnect between the views of those handling the findings of research and those participating in research. Exploring, evaluating and ultimately addressing this disconnect should form a priority for researchers and clinicians alike. This social sciences study offers the largest dataset, published to date, of attitudes towards issues surrounding the return of IFs from sequencing research

“Not pathogenic until proven otherwise”: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through the 100,000 Genomes Project, which offers participants feedback of limited secondary findings. MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access to GS, and reviews findings. Semistructured interviews were conducted with 19 GM-MDT members to explore perspectives on secondary findings. ResultsWhile enthusiastic about GS for diagnosing rare disease, members question the rationale for genome screening largely because of lack of evidence for clinical utility and limited justification for use of resources. Membersandrsquo; views are drawn from diverse experiences; they feel a strong sense of responsibility to act in participantsandrsquo; best interests. The capacity to return limited secondary findings should be enabled, but members favor a cautious approach that is responsive to accumulating evidence. Informed participant choice is considered critical, yet challenging. Discrimination of variants is considered essential, and requiring of specialist input and consensus. Multiple areas requiring enhanced engagement and education are identified, i.e., for patients, the public, and health-care professionals; at present, mainstreaming of genomics may be premature. ConclusionUK experts believe that evidence to inform policy toward secondary findings is lacking, arguing for caution.</p