Genomic Incidental Findings Research Articles

Next-Generation Phenotyping and Genomic Incidental Findings

Next-Generation Phenotyping and Genomic Incidental Findings

Next-Generation Phenotyping and Genomic Incidental Findings—Reply

Next-Generation Phenotyping and Genomic Incidental Findings—Reply

Paternalism and the ACMG recommendations on genomic incidental findings: patients seen but not heard

To the Editor: Incidental findings that may arise in whole-exome or whole-genome sequencing pose significant challenges for clinical care. The American College of Medical Genetics and Genomics’ (ACMG’s) recent article, “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” establishes routine analysis of pathogenic variants of a list of disease-associated genetic loci as a standard of practice when clinical whole-genome sequencing is done for any reason except prenatal testing.

Recommendations for returning genomic incidental findings? We need to talk!

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines.

Point-counterpoint. Ethics and genomic incidental findings.

Laboratories have an obligation to report clinically beneficial incidental findings.

‘Information is information’: a public perspective on incidental findings in clinical and research genome‐based testing

The potential for genomic incidental findings is increasing with the use of genome-based testing. At the same time approaches to clinical decision making are shifting to shared decision-making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross-section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome-based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.

Genomic Incidental Findings: Reducing the Burden to Be Fair

The disclosure of incidental findings to genomic research participants is a hotly debated issue in bioethics. Gliwa and Berkman (2013) added a provocative twist to this debate by arguing that, prov...

Recommendations for returning genomic incidental findings? We need to talk!

Recommendations for returning genomic incidental findings? We need to talk!

Genetics specialists’ perspectives on disclosure of genomic incidental findings in the clinical setting

ObjectiveEvidence documenting management of incidental findings (IFs) from clinical genomic testing is limited. The aim of this study was to examine genetics specialists’ perspectives regarding current and preferred disclosure of clinical genomic IFs. Methods50 genetics specialists, including medical geneticists, laboratory professionals, genetic counselors, and nurses participated in structured telephone interviews. Data were analyzed using qualitative content analysis and descriptive statistics. ResultsMost specialists had encountered IFs, but definitions of IFs varied. They discussed challenges with informing patients about the prospect of IFs and disclosing IFs to patients. Causing psychological harm to patients was a concern. Participants were divided on whether IFs needed to be clinically significant and/or actionable in order to be disclosed to patients. Creating formal disclosure guidelines was considered useful, but only if they were flexible. Additional counseling, more interdisciplinary communication, maintaining contact with patients, and a centralized database to interpret IFs were also proposed. ConclusionGenetics specialists offer insights into the challenges of defining IFs, knowing when and how to disclose them, and the potential need for flexible disclosure guidelines. Practice implicationsFurther discussion between practicing genetics specialists is needed to develop consensus on the development of best-practice guidelines for IF management.

Critical social theory approach to disclosure of genomic incidental findings

Technology has expanded genomic research and the complexity of extracted gene-related information. Health-related genomic incidental findings pose new dilemmas for nurse researchers regarding the ethical application of disclosure to participants. Consequently, informed consent specific to incidental findings is recommended. Critical Social Theory is used as a guide in recognition of the changing meaning of informed consent and to serve as a framework to inform nursing of the ethical application of disclosure consent in genomic nursing research practices.

Researcher and Institutional Review Board Chair Perspectives on Incidental Findings in Genomic Research

Genomic research can produce findings unrelated to a study's aims. The purpose of this study was to examine researcher and Institutional Review Board (IRB) chair perspectives on genomic incidental findings (GIFs). Nineteen genomic researchers and 34 IRB chairs from 42 institutions participated in semi-structured telephone interviews. Researchers and chairs described GIFs within their respective roles. Few had direct experience with disclosure of GIFs. Researchers favored policies where a case by case determination regarding whether GIF disclosure would be offered after discovery, whereas IRB chairs preferred policies where procedures for disclosure would be determined prior to approval of the research. Researcher and IRB chair perspectives on management of GIFs overlap, but each group provides a unique perspective on decisions regarding disclosure of GIFs in research. Engagement of both groups is essential in efforts to provide guidance for researchers and IRBs regarding disclosure of GIFs in research.

Informed Consent and Genomic Incidental Findings: IRB Chair Perspectives

It is unclear how genomic incidental finding (GIF) prospects should be addressed in informed consent processes. An exploratory study on this topic was conducted with 34 purposively sampled Chairs of institutional review boards (IRBs) at centers conducting genome-wide association studies. Most Chairs (96%) reported no knowledge of local IRB requirements regarding GIFs and informed consent. Chairs suggested consent processes should address the prospect of, and study disclosure policy on, GIFs; GIF management and follow-up; potential clinical significance of GIFs; potential risks of GIF disclosure; an opportunity for participants to opt out of GIF disclosure; and duration of the researcher's duty to disclose GIFs. Chairs were concerned about participant disclosure preferences changing over time; inherent limitations in determining the scope and accuracy of claims about GIFs; and making consent processes longer and more complex. IRB Chair and other stakeholder perspectives can help advance informed consent efforts to accommodate GIF prospects.