The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients

A pilot randomized trial

MedSeq Project

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT 01736566) Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audiorecorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalAnnals of Internal Medicine
Volume167
Issue number3
DOIs
StatePublished - Aug 1 2017

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Primary Health Care
Genome
Primary Care Physicians
Health Behavior
Variegate Porphyria
Delivery of Health Care
Sample Size
Medical Records
Phenotype

ASJC Scopus subject areas

  • Internal Medicine

Cite this

The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients : A pilot randomized trial. / MedSeq Project.

In: Annals of Internal Medicine, Vol. 167, No. 3, 01.08.2017, p. 159-169.

Research output: Contribution to journalArticle

@article{8dd128a7e33447abba149972b6d14672,
title = "The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients: A pilot randomized trial",
abstract = "Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT 01736566) Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audiorecorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58{\%} of patients were female. Eleven FH + WGS patients (22{\%} [95{\%} CI, 12{\%} to 36{\%}]) had new MDR results. Only 2 (4{\%} [CI, 0.01{\%} to 15{\%}]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16{\%} (CI, 8{\%} to 30{\%}) of FH patients and 34{\%} (CI, 22{\%} to 49{\%}) of FH + WGS patients. Thirty percent (CI, 17{\%} to 45{\%}) and 41{\%} (CI, 27{\%} to 56{\%}) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73{\%} [CI, 39{\%} to 99{\%}]) as appropriate and 2 results (18{\%} [CI, 3{\%} to 52{\%}]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.",
author = "{MedSeq Project} and Vassy, {Jason L.} and Christensen, {Kurt D.} and Schonman, {Erica F.} and Blout, {Carrie L.} and Robinson, {Jill O.} and Krier, {Joel B.} and Diamond, {Pamela M.} and Matthew Lebo and Kalotina Machini and Azzariti, {Danielle R.} and Dmitry Dukhovny and Bates, {David W.} and MacRae, {Calum A.} and Murray, {Michael F.} and Rehm, {Heidi L.} and McGuire, {Amy L.} and Green, {Robert C.} and Cirino, {Allison L.} and Ho, {Carolyn Y.} and Lane, {William J.} and Lehmann, {Lisa S.} and Morton, {Cynthia C.} and Perry, {Denise L.} and Seidman, {Christine E.} and Sunyaev, {Shamil R.} and Tiffany Nguyen and Eleanor Steffens and Betting, {Wendi Nicole} and Aronson, {Samuel J.} and Ozge Ceyhan-Birsoy and Lebo, {Matthew S.} and McLaughlin, {Heather M.} and Tsai, {Ellen A.} and Jennifer Blumenthal-Barby and Feuerman, {Lindsay Z.} and Kaitlyn Lee and Slashinski, {Melody J.} and Kelly Davis and Ubel, {Peter A.} and Peter Kraft and Roberts, {J. Scott} and Garber, {Judy E.} and Tina Hambuch and Isaac Kohane and Kong, {Sek Won}",
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TY - JOUR

T1 - The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients

T2 - A pilot randomized trial

AU - MedSeq Project

AU - Vassy, Jason L.

AU - Christensen, Kurt D.

AU - Schonman, Erica F.

AU - Blout, Carrie L.

AU - Robinson, Jill O.

AU - Krier, Joel B.

AU - Diamond, Pamela M.

AU - Lebo, Matthew

AU - Machini, Kalotina

AU - Azzariti, Danielle R.

AU - Dukhovny, Dmitry

AU - Bates, David W.

AU - MacRae, Calum A.

AU - Murray, Michael F.

AU - Rehm, Heidi L.

AU - McGuire, Amy L.

AU - Green, Robert C.

AU - Cirino, Allison L.

AU - Ho, Carolyn Y.

AU - Lane, William J.

AU - Lehmann, Lisa S.

AU - Morton, Cynthia C.

AU - Perry, Denise L.

AU - Seidman, Christine E.

AU - Sunyaev, Shamil R.

AU - Nguyen, Tiffany

AU - Steffens, Eleanor

AU - Betting, Wendi Nicole

AU - Aronson, Samuel J.

AU - Ceyhan-Birsoy, Ozge

AU - Lebo, Matthew S.

AU - McLaughlin, Heather M.

AU - Tsai, Ellen A.

AU - Blumenthal-Barby, Jennifer

AU - Feuerman, Lindsay Z.

AU - Lee, Kaitlyn

AU - Slashinski, Melody J.

AU - Davis, Kelly

AU - Ubel, Peter A.

AU - Kraft, Peter

AU - Roberts, J. Scott

AU - Garber, Judy E.

AU - Hambuch, Tina

AU - Kohane, Isaac

AU - Kong, Sek Won

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT 01736566) Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audiorecorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.

AB - Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT 01736566) Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audiorecorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.

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DO - 10.7326/M17-0188

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JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

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