Effect of Public Deliberation on Attitudes toward Return of Secondary Results in Genomic Sequencing

The increased use of genomic sequencing in clinical diagnostics and therapeutics makes imperative the development of guidelines and policies about how to handle secondary findings. For reasons both practical and ethical, the creation of these guidelines must take into consideration the informed opinions of the lay public. As part of a larger Clinical Sequencing Exploratory Research (CSER) consortium project, we organized a deliberative democracy (DD) session that engaged 66 participants in dialogue about the benefits and risks associated with the return of secondary findings from clinical genomic sequencing. Participants were educated about the scientific and ethical aspects of the disclosure of secondary findings by experts in medical genetics and bioethics, and then engaged in facilitated discussion of policy options for the disclosure of three types of secondary findings: 1) medically actionable results; 2) adult onset disorders found in children; and 3) carrier status. Participants’ opinions were collected via surveys administered one month before, immediately following, and one month after the DD session. Post DD session, participants were significantly more willing to support policies that do not allow access to secondary findings related to adult onset conditions in children (Χ2 (2, N = 62) = 13.300, p = 0.001) or carrier status (Χ2 (2, N = 60) = 11.375, p = 0.003). After one month, the level of support for the policy denying access to secondary findings regarding adult‐onset conditions remained significantly higher than the pre‐DD level, although less than immediately post‐DD (Χ2 (1, N = 60) = 2.465, p = 0.041). Our findings suggest that education and deliberation enhance public appreciation of the scientific and ethical complexities of genome sequencing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/1/jgc40122-sup-0006.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/2/jgc40122.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/3/jgc40122-sup-0005.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/4/jgc40122-sup-0007.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/5/jgc40122-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/6/jgc40122-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/7/jgc40122-sup-0003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146892/8/jgc40122-sup-0004.pd

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

What helps people make values-congruent medical decisions? Eleven strategies tested across six studies

Background: High-quality health decisions are often defined as those that are both evidence-informed and values-congruent. A values-congruent decision aligns with what matters to those most affected by the decision. Values clarification methods are intended to support values-congruent decisions but their effects on values congruence are rarely evaluated. Methods: We tested eleven strategies, including the three most commonly-used values clarification methods, across six between-subjects online randomized experiments in demographically-diverse US populations (n1=1346, n2=456, n3=840, n4=1178, n5=841, n6=2033) in the same hypothetical decision. Our primary outcome was values congruence. Decisional conflict was a secondary outcome in studies 3 through 6. Results: Two commonly-used values clarification methods (pros and cons, rating scales) reduced decisional conflict but did not encourage values-congruent decisions. Strategies using mathematical models to show participants which option aligned with what mattered to them encouraged values-congruent decisions and reduced decisional conflict when assessed. Limitations: A hypothetical decision was necessary for ethical reasons, as we believed some strategies may harm decision quality. Later studies used more outcomes and covariates. Results may not generalize outside US-based adults with online access. We assumed validity and stability of values during the brief experiments. Conclusions: Failing to explicitly support the process of values clarification leads to increased proportions of values-disgruent decisions. Methods representing over half of values clarification methods commonly in use failed to encourage values-congruent decisions. Methods that use models to explicitly show people how options align with their values hold more promise for helping people make decisions aligned with what matters to them. Decisional conflict, while arguably an important outcome in and of itself, is not an appropriate proxy for values congruence

What helps people make values-congruent medical decisions? Eleven strategies tested across six studies

Background: High-quality health decisions are often defined as those that are both evidence-informed and values-congruent. A values-congruent decision aligns with what matters to those most affected by the decision. Values clarification methods are intended to support values-congruent decisions but their effects on values congruence are rarely evaluated. Methods: We tested eleven strategies, including the three most commonly-used values clarification methods, across six between-subjects online randomized experiments in demographically-diverse US populations (n1=1346, n2=456, n3=840, n4=1178, n5=841, n6=2033) in the same hypothetical decision. Our primary outcome was values congruence. Decisional conflict was a secondary outcome in studies 3 through 6. Results: Two commonly-used values clarification methods (pros and cons, rating scales) reduced decisional conflict but did not encourage values-congruent decisions. Strategies using mathematical models to show participants which option aligned with what mattered to them encouraged values-congruent decisions and reduced decisional conflict when assessed. Limitations: A hypothetical decision was necessary for ethical reasons, as we believed some strategies may harm decision quality. Later studies used more outcomes and covariates. Results may not generalize outside US-based adults with online access. We assumed validity and stability of values during the brief experiments. Conclusions: Failing to explicitly support the process of values clarification leads to increased proportions of values-disgruent decisions. Methods representing over half of values clarification methods commonly in use failed to encourage values-congruent decisions. Methods that use models to explicitly show people how options align with their values hold more promise for helping people make decisions aligned with what matters to them. Decisional conflict, while arguably an important outcome in and of itself, is not an appropriate proxy for values congruence