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The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

ABSTRACT: 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.

SUBMITTER: Vassy JL

PROVIDER: S-EPMC4113228 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

Vassy Jason L JL Lautenbach Denise M DM McLaughlin Heather M HM Kong Sek Won SW Christensen Kurt D KD Krier Joel J Kohane Isaac S IS Feuerman Lindsay Z LZ Blumenthal-Barby Jennifer J Roberts J Scott JS Lehmann Lisa Soleymani LS Ho Carolyn Y CY Ubel Peter A PA MacRae Calum A CA Seidman Christine E CE Murray Michael F MF McGuire Amy L AL Rehm Heidi L HL Green Robert C RC

Trials 20140320

<h4>Background</h4>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.<h4>Methods/design</h4>This pair of randomized controlled tri ...[more]

PMID: 24645908

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Project description:ImportanceWhole-genome sequencing (WGS) shows promise as a first-line genetic test for acutely ill infants, but widespread adoption and implementation requires evidence of an effect on clinical management.ObjectiveTo determine the effect of WGS on clinical management in a racially and ethnically diverse and geographically distributed population of acutely ill infants in the US.Design, setting, and participantsThis randomized, time-delayed clinical trial enrolled participants from September 11, 2017, to April 30, 2019, with an observation period extending to July 2, 2019. The study was conducted at 5 US academic medical centers and affiliated children's hospitals. Participants included infants aged between 0 and 120 days who were admitted to an intensive care unit with a suspected genetic disease. Data were analyzed from January 14 to August 20, 2020.InterventionsPatients were randomized to receive clinical WGS results 15 days (early) or 60 days (delayed) after enrollment, with the observation period extending to 90 days. Usual care was continued throughout the study.Main outcomes and measuresThe main outcome was the difference in the proportion of infants in the early and delayed groups who received a change of management (COM) 60 days after enrollment. Additional outcome measures included WGS diagnostic efficacy, within-group COM at 90 days, length of hospital stay, and mortality.ResultsA total of 354 infants were randomized to the early (n = 176) or delayed (n = 178) arms. The mean participant age was 15 days (IQR, 7-32 days); 201 participants (56.8%) were boys; 19 (5.4%) were Asian; 47 (13.3%) were Black; 250 (70.6%) were White; and 38 (10.7%) were of other race. At 60 days, twice as many infants in the early group vs the delayed group received a COM (34 of 161 [21.1%; 95% CI, 15.1%-28.2%] vs 17 of 165 [10.3%; 95% CI, 6.1%-16.0%]; P = .009; odds ratio, 2.3; 95% CI, 1.22-4.32) and a molecular diagnosis (55 of 176 [31.0%; 95% CI, 24.5%-38.7%] vs 27 of 178 [15.0%; 95% CI, 10.2%-21.3%]; P < .001). At 90 days, the delayed group showed a doubling of COM (to 45 of 161 [28.0%; 95% CI, 21.2%-35.6%]) and diagnostic efficacy (to 56 of 178 [31.0%; 95% CI, 24.7%-38.8%]). The most frequent COMs across the observation window were subspecialty referrals (39 of 354; 11%), surgery or other invasive procedures (17 of 354; 4%), condition-specific medications (9 of 354; 2%), or other supportive alterations in medication (12 of 354; 3%). No differences in length of stay or survival were observed.Conclusions and relevanceIn this randomized clinical trial, for acutely ill infants in an intensive care unit, introduction of WGS was associated with a significant increase in focused clinical management compared with usual care. Access to first-line WGS may reduce health care disparities by enabling diagnostic equity. These data support WGS adoption and implementation in this population.Trail registrationClinicalTrials.gov Identifier: NCT03290469.

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The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

Publications

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

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