Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing.
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ABSTRACT:
SUBMITTER: Robinson JO
PROVIDER: S-EPMC4842131 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing.
Robinson Jill Oliver JO Carroll Thomas M TM Feuerman Lindsay Z LZ Perry Denise L DL Hoffman-Andrews Lily L Walsh Rebecca C RC Christensen Kurt D KD Green Robert C RC McGuire Amy L AL
Journal of empirical research on human research ethics : JERHRE 20160228 1
An increasing number of individuals are being recruited to whole genome sequencing (WGS) research. When asked hypothetically, the majority of the public express willingness to participate in this type of research, yet little is known about how many individuals will actually consent to research participation or what they perceive the risks to be. The MedSeq Project is a clinical trial exploring WGS in clinical care. We documented primary reason(s) for declining participation and reviewed audio-re ...[more]
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Project description:BackgroundClinical genome and exome sequencing (CGES) is being used in an expanding range of clinical settings. Most approaches to offering patients choices about learning CGES results classify results according to expert definitions of clinical actionability. Little is known about how patients conceptualize different categories of CGES results.MethodsThe MedSeq Project is a randomized controlled trial studying the use of whole-genome sequencing (WGS) in primary care and cardiology. We surveyed 202 patient-participants about different kinds of WGS results and conducted qualitative interviews with 49 of these participants. Interview data were analyzed both inductively and deductively using thematic content analysis.ResultsParticipants demonstrated high levels of study understanding and genetic literacy. A small majority of participants wanted to learn all of their WGS results (n = 123, 61%). Qualitative data provided a deeper understanding of participants' perspectives about different types of WGS results. Participants did not have the same views about which WGS results would be actionable or upsetting to learn. They conceptualized variants of uncertain significance (VUS) in a variety of different ways. Many participants expressed optimism that the uncertainty associated with VUS results could be reduced over time.ConclusionsProposals to determine which WGS/CGES results to disclose by soliciting patient preferences may fail to appreciate the complex ways patients think about disease and the information WGS/CGES can produce. Our findings challenge prevailing methods of facilitating patient choice and assessing the benefits and harms related to the return of WGS/CGES results, which mostly rely on expert definitions of clinical utility to categorize the kinds of results patients can learn.
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Project description:Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients' genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results.The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.ClinicalTrials.gov identifier NCT01736566.
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Project description:PurposeDisease-causing mutations and pharmacogenomic variants are of primary interest for clinical whole-genome sequencing. However, estimating genetic liability for common complex diseases using established risk alleles might one day prove clinically useful.MethodsWe compared polygenic scoring methods using a case-control data set with independently discovered risk alleles in the MedSeq Project. For eight traits of clinical relevance in both the primary-care and cardiomyopathy study cohorts, we estimated multiplicative polygenic risk scores using 161 published risk alleles and then normalized them using the population median estimated from the 1000 Genomes Project.ResultsOur polygenic score approach identified the overrepresentation of independently discovered risk alleles in cases as compared with controls using a large-scale genome-wide association study data set. In addition to normalized multiplicative polygenic risk scores and rank in a population, the disease prevalence and proportion of heritability explained by known common risk variants provide important context in the interpretation of modern multilocus disease risk models.ConclusionOur approach in the MedSeq Project demonstrates how complex trait risk variants from an individual genome can be summarized and reported for the general clinician and also highlights the need for definitive clinical studies to obtain reference data for such estimates and to establish clinical utility.
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