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

Abstract

Purpose:As whole-exome sequencing (WES) and whole-genome sequencing (WGS) move into routine clinical practice, it is timely to review data that might inform the debate regarding 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:Forty-four 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, whereas views of genomics professionals were informed by a sense of professional responsibility. Experience with 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.Genet Med 19 3, 283–293.

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients

“…This may well be counterproductive, because many patients are very eager to receive at‐least actionable findings. This is consistent with other qualitative and quantitative studies that show that an overwhelming majority of patients would opt to know these results . Thus, an opt‐out is vital to ensure that patients feel respected but will hardly be used in practice.…”

“…Several studies have shown that patients are generally positive about receiving unsolicited findings . This also holds true for cancer patients, but research suggests that patients become more cautious to receive all types of risk information when they are informed about the potential consequences for themselves and their family members . The possibility of encountering unsolicited findings makes clinical decision making in oncology even more complex, and a thoughtful disclosure policy is needed.…”

Ethical values supporting the disclosure of incidental and secondary findings in clinical genomic testing: a qualitative study

“…Arguments for this cautiousness are the possibility of physical and/or emotional harm (by overwhelming patients with unnecessary or harmful tests, diagnoses or interventions) and hence the professional duty of non-maleficence [3,8]. When IFs are unintentionally identified, these results should only be disclosed if they are highly significant, highly penetrant and medically actionable [17][18][19].…”

Why Patients Decline Genomic Sequencing Studies: Experiences from the CSER Consortium

“…Privacy and confidentiality have also been cited as reasons for declining participation in genome-wide association studies and repository-based research (Trinidad et al 2010). Participating in GS research presents distinctive considerations including the prospect of identifying unexpected or secondary findings (Mackley et al 2017), uncovering genetic variants in children that relate to adult onset conditions (Wilfond et al 2015), and disclosing carrier status findings in individuals not specifically seeking this information for reproductive reasons (Himes et al 2017). Though a lot is known about reasons for declining clinical genetic testing and genetic research, there is still much to explore regarding reasons patients decline GS.…”