Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice

<p>Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice</p

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

Disorders of sex development: effect of molecular diagnostics

Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs

How do research participants perceive “uncertainty” in genome sequencing?

PURPOSE: The scope of uncertainty in genome sequence information has no rival in health-care delivery. We present data from adults participating in a National Institutes of Health study using this technology, in which perceptions of uncertainty are hypothesized to be key in predicting decisions to learn and act on genome health information. METHODS: We conducted six professionally moderated focus groups with 39 randomly selected ClinSeq participants varying on whether they had coronary heart disease and had received prior sequence results. We elicited perceptions of the uncertainties associated with genome sequencing using written prompts. RESULTS: Participants perceived uncertainty as a quality of genome information. The majority of participants characterized uncertainty of sequencing information as changing, fluid, developing, or ground breaking. These responses led to anticipation of more optimistic future outcomes. Fewer participants described uncertainty as questionable, less accurate, limited, or poorly understood. These perceptions seemed to undermine participants\u27 faith in genome information, leading to feelings of disillusionment. CONCLUSION: Our findings suggest that perceptions of uncertainty are related to epistemological beliefs that inform expectations for the information. Interventions that promote realistic expectations of genome sequencing may mitigate negative responses to uncertainty

Patient hopes for diagnostic genomic sequencing: roles of uncertainty and social status

For patients with unexplained or undiagnosed conditions, genomic sequencing offers the hope of resolving unanswered questions. With the growth of clinical genomic sequencing, understanding factors that shape patients' hope for information could have important implications for developing patient education guidelines. Based on the goal-directed theory of hope, we investigated illness uncertainty as a form of motivation and subjective social status as a form of perceived resources to predict the amount and kinds of information that adult patients (N=191) and parents of pediatric patients (N=79) hoped to receive from diagnostic sequencing results. Participants were part of a larger longitudinal study on clinical genomic sequencing, but the current study focuses on their hopes for diagnostic sequencing results. Hopes for information were assessed through close-ended and open-ended responses. Findings from mixed methods analyses indicated that although patients and parents hoped to learn multiple kinds of information from diagnostic sequencing results, their hopes appeared to be influenced by their illness uncertainty and perceptions of their social and economic resources. These findings suggest that patients' illness uncertainty and perceived resources could be useful avenues for discussing patient hopes and educating patients about strengths and limitations of genomic sequencing