CompletedNCT01736566Updated Aug 27, 2024Results posted

A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare

An interventional study of Family History + Whole Genome Sequencing and Family History Only in Healthy Adults (Full Study and Extension Phase) and Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-27.

Sponsored by Brigham and Women's Hospital · Not applicable, Interventional, and Health services research

From the registry’s dates

Registered 8 months after the study started (first participant enrolled Dec 2011, registered Aug 2012).

Phase: Not applicable
Study type: Interventional
Enrollment: 213
Allocation: Randomized
Ages: 18 Years to 90 Years
Sex: All

Study summary

The MedSeq™ Project seeks to explore the impact of incorporating information from a patient's whole genome sequence into the practice of clinical medicine. In the extension phase of MedSeq we are attempting increase our participant diversity by increasing targeted enrollment of African/African American patient participants.

Read the detailed description

Whole genome sequencing (WGS) and whole exome sequencing (WES) services are currently available to and are being utilized by physicians and their patients in both research and clinical settings. The widespread availability and use of WGS and WES in the practice of clinical medicine is imminent. In the very near future, sequencing of individual genomes will be inexpensive and ubiquitous, and patients will be looking to the medical establishment for interpretations, insight and advice to improve their health. Developing standards and procedures for the use of WGS information in clinical medicine is an urgent need, but there are numerous obstacles related to integrity and storage of WGS data, interpretation and responsible clinical integration. MedSeq™ seeks to develop a process to integrate WGS into clinical medicine and explore the impact of doing so.

We believe that WGS will be used in many ways, including two distinct and complementary situations. In generally healthy patients, physicians will use the results of WGS to derive insight into future health risks and inform prevention and surveillance efforts, a category we refer to as General Genomic Medicine. In patients presenting with a family history or symptoms of a disease, physicians will use the results of WGS to interrogate particular sets of genes known to be associated with the disease in question, a category we refer to as Disease-Specific Genomic Medicine.

Beginning in fall 2012, we will enroll 10 primary care physicians and 100 of their healthy middle-aged patients to evaluate the use of General Genomic Medicine, and 10 cardiologists and 100 of their patients presenting with hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) to evaluate the use of Disease-Specific Genomic Medicine. We will randomize physicians and their patients within each of the above models to receive clinically meaningful information derived from WGS versus current standard of care without the use of WGS.

MedSeq™ is comprised of three distinct but highly collaborative projects. Project 1 will enroll physicians and patients into the protocol, educate the physicians on basic genomic principles and safely monitor the use of genomic information in clinical practice. Project 2 will use a WGS analysis/interpretation pipeline to generate a genome report on each patient randomized to receive WGS in this protocol. Project 3 will examine preferences and motivations of physicians and patients enrolled, evaluate the flow and utilization of genomic information within the clinical interactions, and assess understanding, behavior, medical consequences and healthcare costs associated with the use of WGS in these models of medical practice.

In an extension phase of the study, we will 1) recruit approximately 10-15 patient-participants who self-identify as African or African American, whose physicians deem to be healthy. All will be placed in the whole genome-sequencing arm of the study. They will undergo the same activities as traditional MedSeq participants except for randomization. 2) We will conduct a targeted phenotype assessment on MedSeq Project patient-participants who are identified to have a monogenic finding. We plan to perform additional analysis by reviewing their medical records and looking specifically with their variant in mind to see if features associated with the variants were known prior to the study or were identified by further testing or by their physical during the course of the study.

This initiative will significantly accelerate the use of genomics in clinical medicine by creating and safely testing novel methods for integrating information from WGS into physicians' care of patients.

Conditions studied

Healthy Adults (Full Study and Extension Phase)
Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy

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Keywords

Primary Care
Cardiology
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Whole Genome Sequencing

In context

Cardiomyopathies

1,176 studies on the registry are indexed under Cardiomyopathies; 287 are open to participants now.

This study's enrollment of 213 is above the median of 51 across 609 interventional studies indexed under Cardiomyopathies.

Browse Cardiomyopathies studies →

Lead sponsor

Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.

Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 90 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

Note for Age Eligibility:

Cardiology patients 18 Years to 90 Years OR
Primary Care Patients 40 Years to 65 Years (Adult, Senior)

Inclusion Criteria:

Primary Care

Generally healthy (as defined by the primary care provider) adult patients at Brigham and Women's Hospital ages 40-65. All patients must be fluent in English.

Cardiology

Patients in the Partners Healthcare System who are 18 years or older with a diagnosis of hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) and a family history of HCM or DCM who previously had or who are candidates for targeted HCM or DCM genetic testing through routine clinical practice within Partners. All patients must be fluent in English.

Exclusion Criteria:

Primary Care

Patients who do not meet the above criteria. Patients with cardiac disease or a progressive debilitating illness. Patients who are pregnant or patients whose spouses/significant others are pregnant. Patients with untreated clinical anxiety or depression (as measured by a Hospital Anxiety and Depression Scale (HADS) score > 11 administered at the baseline study visit.)

Cardiology

Patients who do not meet the above criteria. Patients with a progressive debilitating illness. Patients who are pregnant or patients whose spouses/significant others are pregnant. Patients with untreated clinical anxiety or depression (as measured by a Hospital Anxiety and Depression Scale (HADS) score > 11 administered at the baseline study visit.)

Extension Phase - Additional Inclusion Criteria

Part 1:

Above inclusion and exclusion criteria PLUS:
Inclusion: Self-identify as African or African American.

Part 2:

Inclusion Criteria

MedSeq participants determined to have a monogenic finding

Exclusion Criteria

Participants not previously enrolled in MedSeq Project
Participants not identified to have a monogenic finding

Study design

Phase: Not applicable
Primary purpose: Health services research
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 213 participants (actual)

Study arms

Experimental
Family History + Whole Genome Sequencing
Doctors and their patients receive a Genome Report and an Annotated Family History Report.
Other: Family History + Whole Genome Sequencing
Active comparator
Family History Only
Doctors and their patients receive an Annotated Family History Report only.
Other: Family History Only

Interventions

OtherFamily History + Whole Genome Sequencing
Doctors and their patients receive a Genome Report and a Family History report. There are two sections of the Genome Report: 1. The General Genome Report, which include highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contain genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing \*In the main study participants are randomized to either the Experimental or Other Arm, in the Extension phase of the study all participants are in the Experimental Arm.
OtherFamily History Only
Doctors and their patients receive a Family History report.

What researchers measure

Primary outcomes

Change in Attitudes and Trust
Adapted measures (Hall, MA, et al. 2006) assessed participants' attitudes toward genetic information, trust of their physicians and the medical system regarding interpretation and use of genetic information. Higher scores on a 12-60 scale represent more positive attitudes and greater trust.
Time frame: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline
Change in Self Efficacy
Assessed through a scale developed for the Multiplex Initiative (Kaphingst, K.A., et al. 2012). Higher scores on a 0-24 scale indicate greater confidence in participants' abilities to understand genetic information.
Time frame: Baseline and 6-months post-results disclosure (6 mos. follow-up administered approx. 17 months after baseline)
Change in Preferences for WGS Information
Through nine novel survey items, participants were asked about their preferences for the types of genetic testing results they would like to receive from their whole genome sequence. Scores on an 0-9 scale represent the change in the number of categories of types of genetic testing results out of 9 that participants wanted to learn about from Baseline to 6-weeks follow-up.
Time frame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
Change in Perceived Health
A single-item measure assessed how participants perceived their own health on a 1-5 scale. Adapted from the SF-12 (DeSalvo KB, Qual Life Res, 2006). Higher scores indicate more positive perceptions of health at follow-up
Time frame: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (6 mos. follow-up follow-up administered approx. 17 months after baseline)
Change in Shared Decision Making
Changes in shared decision making were assessed through a single item adapted from the Control Preferences Scale, a measure designed to ascertain the degree of control an individual wants to assume when decisions are being made about medical treatment. Higher scores on a scale of 1-3 indicate preferences towards more equally shared decision making (Heisler et al 2003). Higher mean changes over time indicate a change in preference towards more equally shared decision making at follow-up.
Time frame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
Change in Intolerance of Uncertainty
Changes in participants' tolerance for uncertainty were assessed through a short 12-item version of the Intolerance of Uncertainty Scale (Carleton, 2007). Total summed scale range is 12-60, with higher scores indicating increased negative feelings about uncertainty from baseline to follow-up.
Time frame: Baseline and 6-months post-disclosure (6 mos. follow-up administered approx. 17 mos. after baseline)
Change in General Anxiety and Depression
The Hospital Anxiety and Depression Scale (HADS) scale was administered through a survey. This is a validated scale designed to assess the participants' level of depression and anxiety through Likert-type questions. Total ranges for each summed subscale, anxiety and depression, is 0-21. Any participant scoring \>14 on the anxiety subscale or \>16 on the depression subscale were contacted by study staff for evaluation. Higher scores indicate increased anxiety or depression from baseline to follow-up.
Time frame: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos and 6 mos follow-up approx 17 mos. after baseline)
Change in Health Behaviors
Novel items that asked whether participants changed vitamin use, supplement use, medication use, diet, exercise, or "other" health behaviors. Counts and percentages represent participants who reported any health behavior changes.
Time frame: 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Information Sharing
Sharing of information was assessed by asking patients if they intended to share results with others (at the end of the disclosure visit) and if they had shared their results with others (6 months after disclosure) adapted from the Health Information National Trends Survey (HINTS).
Time frame: At the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (approx. 17 mos. after baseline)
Changes in Genomic Literacy
Changes in participants' genomic literacy were measured with an 11-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline and 6 months post-disclosure. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 11, with higher scores indicating higher genomic literacy.
Time frame: Assessing Genomic Literacy at baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
Changes in Health Care Utilization
Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Changes are assessed by comparing the number of services and procedures received in 6 months following disclosure against the number of services and procedures received in the 6 months prior to disclosure.
Time frame: 6 months prior to disclosure and 6-months post-disclosure (approx. 17 mos. after baseline) and 5-years post-disclosure
Change in Perceived Utility
A novel survey item asked participants to rate the usefulness of whole genome sequencing results for managing health on a 1-10 scale. Scores at 6 months were compared to scores at baseline.
Time frame: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)

Secondary outcomes

Psychological Impact
Psychological impact was assessed by a modified version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire. Higher scores indicated more distress related to study results.
Time frame: 6-weeks post-disclosure and 6-months post-disclosure (6wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Decisional Regret
Participants' satisfaction with their decision to participate in the MedSeq Project through a 5-item validated scale (Brehaut 2003). Average score computed after reversing scores of 2 negatively phrased items and converting score to range from 0-100 by subtracting 1 and multiplying by 25. Higher scores indicate greater regret.
Time frame: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Understanding
A novel item assessed participants' subjective understanding of their study results on a 1-5 scale, where higher scores indicate greater subjective understanding.
Time frame: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Expectations
Novel survey items asked participants about whether or not their genetic test results would be useful for specific reasons. Response options were "no," "probably not", "probably yes," and "yes." Responses of "probably yes" and "yes" were combined to simplify presentation of data.
Time frame: Baseline

Results

Posted Nov 7, 2018

Participant flow

Participant recruitment began in 2012 at Brigham and Women's hospital by letter, email, phone and in person.

Main Study

Participant flow — Main Study
Milestone	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing: Cardiology	Family History Only: Cardiology	Extension Cohort
Started	51	50	50	52	10
Completed	50	50	49	51	6
Not completed	1	0	1	1	4

Long Term Follow-up

Participant flow — Long Term Follow-up
Milestone	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing: Cardiology	Family History Only: Cardiology	Extension Cohort
Started	26	16	25	25	4
Completed	26	16	25	25	4
Not completed	0	0	0	0	0

Outcome measures

PrimaryChange in Attitudes and Trust

Adapted measures (Hall, MA, et al. 2006) assessed participants' attitudes toward genetic information, trust of their physicians and the medical system regarding interpretation and use of genetic information. Higher scores on a 12-60 scale represent more positive attitudes and greater trust.

Time frame:: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline
Reported as:: Mean · units on a scale

Change in Attitudes and Trust
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Change in Attitudes and Trust	0.0 ± 5.3	0.7 ± 4.5	3.5 ± 5.1	1.8 ± 3.5	1.0 ± 6.3

PrimaryChange in Self Efficacy

Assessed through a scale developed for the Multiplex Initiative (Kaphingst, K.A., et al. 2012). Higher scores on a 0-24 scale indicate greater confidence in participants' abilities to understand genetic information.

Time frame:: Baseline and 6-months post-results disclosure (6 mos. follow-up administered approx. 17 months after baseline)
Reported as:: Mean · units on a scale

Change in Self Efficacy
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Extension Cohort
Change in Self Efficacy	0.3 ± 3.4	0.5 ± 4.3	3.1 ± 5.7

PrimaryChange in Preferences for WGS Information

Through nine novel survey items, participants were asked about their preferences for the types of genetic testing results they would like to receive from their whole genome sequence. Scores on an 0-9 scale represent the change in the number of categories of types of genetic testing results out of 9 that participants wanted to learn about from Baseline to 6-weeks follow-up.

Time frame:: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
Reported as:: Mean · units on a scale

Change in Preferences for WGS Information
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Change in Preferences for WGS Information	-.1 ± 1.5	0.2 ± 2.1	0 ± 2.0	.4 ± 2.3	0.0 ± 1.9

PrimaryChange in Perceived Health

A single-item measure assessed how participants perceived their own health on a 1-5 scale. Adapted from the SF-12 (DeSalvo KB, Qual Life Res, 2006). Higher scores indicate more positive perceptions of health at follow-up

Time frame:: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (6 mos. follow-up follow-up administered approx. 17 months after baseline)
Reported as:: Mean · units on a scale

Change in Perceived Health
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing: Cardiology	Family History Only: Cardiology	Extension Cohort
Change at disclosure	-0.1 ± 0.6	0 ± 0.6	0 ± 0.6	-0.2 ± 0.7	0.3 ± 0.5
Change at 6 months post-disclosure	-0.1 ± 0.7	-0.1 ± 0.7	-0.1 ± 0.8	-0.3 ± 0.8	0.1 ± 0.4

PrimaryChange in Shared Decision Making

Changes in shared decision making were assessed through a single item adapted from the Control Preferences Scale, a measure designed to ascertain the degree of control an individual wants to assume when decisions are being made about medical treatment. Higher scores on a scale of 1-3 indicate preferences towards more equally shared decision making (Heisler et al 2003). Higher mean changes over time indicate a change in preference towards more equally shared decision making at follow-up.

Time frame:: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
Reported as:: Mean · units on a scale

Change in Shared Decision Making
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Change in Shared Decision Making	0.1 ± 0.7	0 ± 0.5	0.2 ± 0.8	0.1 ± 0.7	-0.2 ± 0.8

PrimaryChange in Intolerance of Uncertainty

Changes in participants' tolerance for uncertainty were assessed through a short 12-item version of the Intolerance of Uncertainty Scale (Carleton, 2007). Total summed scale range is 12-60, with higher scores indicating increased negative feelings about uncertainty from baseline to follow-up.

Time frame:: Baseline and 6-months post-disclosure (6 mos. follow-up administered approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Change in Intolerance of Uncertainty
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Change in Intolerance of Uncertainty	-0.5 ± 6.3	0.3 ± 6.6	-1.3 ± 5.8	0 ± 7.4	4.9 ± 14.4

PrimaryChange in General Anxiety and Depression

The Hospital Anxiety and Depression Scale (HADS) scale was administered through a survey. This is a validated scale designed to assess the participants' level of depression and anxiety through Likert-type questions. Total ranges for each summed subscale, anxiety and depression, is 0-21. Any participant scoring \>14 on the anxiety subscale or \>16 on the depression subscale were contacted by study staff for evaluation. Higher scores indicate increased anxiety or depression from baseline to follow-up.

Time frame:: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos and 6 mos follow-up approx 17 mos. after baseline)
Reported as:: Mean · units on a scale

Change in General Anxiety and Depression
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Change in Anxiety at disclosure	0.1 ± 2.3	-.2 ± 2.8	-.4 ± 1.9	-.3 ± 2.8	-0.5 ± 1.5
Change in Anxiety at 6 Weeks	-1.4 ± 3.2	-.8 ± 2.3	-1.7 ± 2.6	-1.0 ± 2.4	-1.5 ± 1.5
Change in Anxiety at 6 Months	-.2 ± 2.6	-.1 ± 2.6	-.2 ± 2.4	-.4 ± 2.4	-0.9 ± 3.0
Change in Depression at disclosure	0 ± 2.1	0.7 ± 2.6	-0.1 ± 1.6	0 ± 2.0	-0.3 ± 2.8
Change in Depression at 6 Weeks	-.3 ± 2.1	0.4 ± 2.7	-.8 ± 1.7	-.2 ± 1.8	-1.0 ± 2.8
Change in Depression at 6 Months	-.1 ± 1.9	0.5 ± 2.1	-.1 ± 1.9	0 ± 1.8	0.9 ± 3.8

PrimaryChange in Health Behaviors

Novel items that asked whether participants changed vitamin use, supplement use, medication use, diet, exercise, or "other" health behaviors. Counts and percentages represent participants who reported any health behavior changes.

Time frame:: 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Reported as:: Count of participants · Participants

Change in Health Behaviors
Participants	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
6 Weeks Post-Disclosure	24	16	17	15	4
6 Months Post-Disclosure	20	13	26	20	3

PrimaryInformation Sharing

Sharing of information was assessed by asking patients if they intended to share results with others (at the end of the disclosure visit) and if they had shared their results with others (6 months after disclosure) adapted from the Health Information National Trends Survey (HINTS).

Time frame:: At the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (approx. 17 mos. after baseline)
Reported as:: Count of participants · Participants

Information Sharing
Participants	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Plans to share at disclosure	43	39	42	30	6
Shared, per 6 month survey	41	27	38	28	4

PrimaryChanges in Genomic Literacy

Changes in participants' genomic literacy were measured with an 11-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline and 6 months post-disclosure. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 11, with higher scores indicating higher genomic literacy.

Time frame:: Assessing Genomic Literacy at baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Changes in Genomic Literacy
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Changes in Genomic Literacy	-.4 ± 1.8	-.5 ± 2.3	-.6 ± 2.1	-.2 ± 1.2	0.0 ± 1.6

PrimaryChanges in Health Care Utilization

Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Changes are assessed by comparing the number of services and procedures received in 6 months following disclosure against the number of services and procedures received in the 6 months prior to disclosure.

Time frame:: 6 months prior to disclosure and 6-months post-disclosure (approx. 17 mos. after baseline) and 5-years post-disclosure
Reported as:: Mean · units on a scale

Changes in Health Care Utilization
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Visits	3.9 ± 7.9	2.3 ± 6.8	1.7 ± 7.8	1.7 ± 7.1	0.6 ± 3.7
Labs	1.4 ± 8.9	-0.3 ± 7.8	1.5 ± 10.6	1.5 ± 7.4	0.5 ± 1.2
Imaging tests	0 ± 2.1	-.1 ± 2.6	0.9 ± 2.1	1.0 ± 1.7	0.0 ± 0.0
Cardiology tests	0.2 ± 1.0	0.2 ± 0.8	0.8 ± 2.7	0.9 ± 3.0	0.3 ± 0.6
Hospitalizations	0 ± 0.1	0 ± 0.2	0.1 ± 0.6	0.1 ± 0.7	0.0 ± 0.0

PrimaryChange in Perceived Utility

A novel survey item asked participants to rate the usefulness of whole genome sequencing results for managing health on a 1-10 scale. Scores at 6 months were compared to scores at baseline.

Time frame:: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Change in Perceived Utility
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Extension Cohort
Change in Perceived Utility	-.6 ± 2.5	-.9 ± 3.0	-1.0 ± 2.3

SecondaryPsychological Impact

Psychological impact was assessed by a modified version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire. Higher scores indicated more distress related to study results.

Time frame:: 6-weeks post-disclosure and 6-months post-disclosure (6wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Psychological Impact
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
6 Weeks Post-Disclosure	13.2 ± 3.8	15.1 ± 3.9	14.2 ± 4.8	14.5 ± 4.3	11.4 ± 4.2
6 Months Post-Disclosure	14.9 ± 3.2	15.2 ± 3.7	16.0 ± 5.4	16.5 ± 5.6	14.1 ± 3.5

SecondaryDecisional Regret

Participants' satisfaction with their decision to participate in the MedSeq Project through a 5-item validated scale (Brehaut 2003). Average score computed after reversing scores of 2 negatively phrased items and converting score to range from 0-100 by subtracting 1 and multiplying by 25. Higher scores indicate greater regret.

Time frame:: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Decisional Regret
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Post-Disclosure	8.9 ± 16.7	12.9 ± 14.0	6.2 ± 9.6	15.8 ± 22.8	6.1 ± 10.8
6 Weeks Post-Disclosure	9.8 ± 16.6	17.2 ± 15.5	5.8 ± 9.7	15.0 ± 20.6	6.4 ± 11.1
6 Months Post-Disclosure	11.5 ± 18.2	19.9 ± 19.3	7.9 ± 11.2	11.3 ± 15.9	4.2 ± 10.2

SecondaryUnderstanding

A novel item assessed participants' subjective understanding of their study results on a 1-5 scale, where higher scores indicate greater subjective understanding.

Time frame:: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
Reported as:: Mean · units on a scale

Understanding
units on a scale	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Post-Disclosure	4.2 ± 0.7	4.5 ± 0.7	4.0 ± 0.7	4.2 ± 0.8	3.9 ± 0.7
6 Weeks Post-Disclosure	4.2 ± 0.8	4.2 ± 0.9	4.1 ± 0.7	4.2 ± 0.9	4.0 ± 0.6
6 Months Post-Disclosure	4.0 ± 0.7	4.3 ± 0.7	4.0 ± 0.8	4.2 ± 0.7	4.0 ± 0.6

SecondaryExpectations

Novel survey items asked participants about whether or not their genetic test results would be useful for specific reasons. Response options were "no," "probably not", "probably yes," and "yes." Responses of "probably yes" and "yes" were combined to simplify presentation of data.

Time frame:: Baseline
Reported as:: Count of participants · Participants

Expectations
Participants	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort
Identify disease risk	40	36	41	42	8
Influence treatment	43	44	41	44	10
Influence medical care	44	46	40	44	9
Influence medications	35	41	36	35	10
Influence end-of-life planning	27	19	25	22	7
Influence reproductive decisions	18	8	24	16	4

Adverse events

Collected over Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Family History + Whole Genome Sequencing: Primary Care	0/51 (0%)	0/51 (0%)	0/51 (0%)
Family History Only: Primary Care	0/50 (0%)	0/50 (0%)	3/50 (6%)
Family History + Whole Genome Sequencing: Cardiology	3/50 (6%)	3/50 (6%)	0/50 (0%)
Family History Only: Cardiology	1/52 (1.9%)	1/52 (1.9%)	0/52 (0%)
Extension Cohort	0/10 (0%)	0/10 (0%)	0/10 (0%)

Most frequent serious events

Most frequent serious events
Event	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing: Cardiology	Family History Only: Cardiology	Extension Cohort
SeriousCardiac disorders	0/51	0/50	3/50	1/52	0/10
DeathCardiac disorders	—	—	3/50	1/52	—

Most frequent other events

Most frequent other events
Event	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing: Cardiology	Family History Only: Cardiology	Extension Cohort
OtherPsychiatric disorders	0/51	3/50	0/50	0/52	0/10

Baseline characteristics

Randomized participants who provided information on the baseline survey (main study), or participants who attended disclosure sessions (extension cohort)

Age, Categorical
Age, Categorical(Participants)	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort	Total
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	49	47	32	36	10	174
>=65 years	2	3	18	16	0	39

Age, Continuous
Age, Continuous(years)	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort	Total
Mean	55.2 ± 7.0	54.6 ± 7.6	55.9 ± 16.1	55.9 ± 12.2	51.4 ± 8.3	55.4 ± 11.3

Sex: Female, Male
Sex: Female, Male(Participants)	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort	Total
Female	29	30	24	19	7	109
Male	22	20	26	33	3	104

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	3	0	1	1	0	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	1	2	3	0	10	16
White	46	43	45	47	0	181
More than one race	0	2	0	1	0	3
Unknown or Not Reported	1	3	1	3	0	8

Region of Enrollment
Region of Enrollment(participants)	Family History + Whole Genome Sequencing: Primary Care	Family History Only: Primary Care	Family History + Whole Genome Sequencing - Cardiology	Family History Only: Cardiology	Extension Cohort	Total
United States	51	50	50	52	10	213

Study locations

1 site

Brigham and Women's Hospital
Boston, Massachusetts 02115, United States

References and documents

Publications

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Brehaut JC, O'Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, Feldman-Stewart D. Validation of a decision regret scale. Med Decis Making. 2003 Jul-Aug;23(4):281-92. doi: 10.1177/0272989X03256005. PubMed 12926578 ↗
Jarvik GP, Amendola LM, Berg JS, Brothers K, Clayton EW, Chung W, Evans BJ, Evans JP, Fullerton SM, Gallego CJ, Garrison NA, Gray SW, Holm IA, Kullo IJ, Lehmann LS, McCarty C, Prows CA, Rehm HL, Sharp RR, Salama J, Sanderson S, Van Driest SL, Williams MS, Wolf SM, Wolf WA; eMERGE Act-ROR Committee and CERC Committee; CSER Act-ROR Working Group; Burke W. Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am J Hum Genet. 2014 Jun 5;94(6):818-26. doi: 10.1016/j.ajhg.2014.04.009. Epub 2014 May 8. PubMed 24814192 ↗
Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014 Jun 19;370(25):2418-25. doi: 10.1056/NEJMra1312543. No abstract available. PubMed 24941179 ↗
Arndt AK, MacRae CA. Genetic testing in cardiovascular diseases. Curr Opin Cardiol. 2014 May;29(3):235-40. doi: 10.1097/HCO.0000000000000055. PubMed 24717670 ↗
Hwang KB, Lee IH, Park JH, Hambuch T, Choe Y, Kim M, Lee K, Song T, Neu MB, Gupta N, Kohane IS, Green RC, Kong SW. Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods. Hum Mutat. 2014 Aug;35(8):936-44. doi: 10.1002/humu.22587. Epub 2014 Jun 24. PubMed 24829188 ↗
Lee IH, Lee K, Hsing M, Choe Y, Park JH, Kim SH, Bohn JM, Neu MB, Hwang KB, Green RC, Kohane IS, Kong SW. Prioritizing disease-linked variants, genes, and pathways with an interactive whole-genome analysis pipeline. Hum Mutat. 2014 May;35(5):537-47. doi: 10.1002/humu.22520. Epub 2014 Mar 6. PubMed 24478219 ↗
Vassy JL, Green RC, Lehmann LS. Genomic medicine in primary care: barriers and assets. Postgrad Med J. 2013 Nov;89(1057):615-6. doi: 10.1136/postgradmedj-2013-132093. No abstract available. PubMed 24129030 ↗
Berg JS, Amendola LM, Eng C, Van Allen E, Gray SW, Wagle N, Rehm HL, DeChene ET, Dulik MC, Hisama FM, Burke W, Spinner NB, Garraway L, Green RC, Plon S, Evans JP, Jarvik GP; Members of the CSER Actionability and Return of Results Working Group. Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium. Genet Med. 2013 Nov;15(11):860-7. doi: 10.1038/gim.2013.133. Epub 2013 Oct 24. Erratum In: Genet Med. 2014 Feb;16(2):203. PubMed 24195999 ↗
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013 Jul;15(7):565-74. doi: 10.1038/gim.2013.73. Epub 2013 Jun 20. Erratum In: Genet Med. 2017 May;19(5):606. doi: 10.1038/gim.2017.18. PubMed 23788249 ↗
McGuire AL, Joffe S, Koenig BA, Biesecker BB, McCullough LB, Blumenthal-Barby JS, Caulfield T, Terry SF, Green RC. Point-counterpoint. Ethics and genomic incidental findings. Science. 2013 May 31;340(6136):1047-8. doi: 10.1126/science.1240156. Epub 2013 May 16. No abstract available. PubMed 23686340 ↗
McGuire AL, McCullough LB, Evans JP. The indispensable role of professional judgment in genomic medicine. JAMA. 2013 Apr 10;309(14):1465-6. doi: 10.1001/jama.2013.1438. No abstract available. PubMed 23571582 ↗
Rehm HL. Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet. 2013 Apr;14(4):295-300. doi: 10.1038/nrg3463. Epub 2013 Mar 12. PubMed 23478348 ↗
Krier JB, Green RC. Management of incidental findings in clinical genomic sequencing. Curr Protoc Hum Genet. 2013;Chapter 9:Unit9.23. doi: 10.1002/0471142905.hg0923s77. PubMed 23595601 ↗
MacRae CA. Action and the actionability in exome variation. Circ Cardiovasc Genet. 2012 Dec;5(6):597-8. doi: 10.1161/CIRCGENETICS.112.965152. No abstract available. PubMed 23250897 ↗
Song T, Hwang KB, Hsing M, Lee K, Bohn J, Kong SW. gSearch: a fast and flexible general search tool for whole-genome sequencing. Bioinformatics. 2012 Aug 15;28(16):2176-7. doi: 10.1093/bioinformatics/bts358. Epub 2012 Jun 23. PubMed 22730434 ↗
Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock DP, Evans JP, Grody WW, Hegde MR, Kalia S, Korf BR, Krantz I, McGuire AL, Miller DT, Murray MF, Nussbaum RL, Plon SE, Rehm HL, Jacob HJ. Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet Med. 2012 Apr;14(4):405-10. doi: 10.1038/gim.2012.21. Epub 2012 Mar 15. PubMed 22422049 ↗
Green RC, Rehm H, Kohane I. Clinical Genome Sequencing. Genomic and Personalized Medicine 2nd Edition: 102- 122, 2012.
Blumenthal-Barby JS, McGuire AL, Green RC, Ubel PA. How behavioral economics can help to avoid 'The last mile problem' in whole genome sequencing. Genome Med. 2015 Jan 22;7(1):3. doi: 10.1186/s13073-015-0132-8. eCollection 2015. PubMed 25614766 ↗
Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med. 2015 Jan 29;372(5):397-9. doi: 10.1056/NEJMp1404776. No abstract available. PubMed 25629736 ↗
Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014 Mar 20;15:85. doi: 10.1186/1745-6215-15-85. PubMed 24645908 ↗
Vassy JL, McLaughlin HM, MacRae CA, Seidman CE, Lautenbach D, Krier JB, Lane WJ, Kohane IS, Murray MF, McGuire AL, Rehm HL, Green RC. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics. 2015;18(2):123-9. doi: 10.1159/000370102. Epub 2015 Jan 21. Erratum In: Public Health Genomics. 2015 Apr;18(3):191. McLaughlin, Heather L [corrected to McLaughlin, Heather M]. PubMed 25612602 ↗
Cirino AL, Lakdawala NK, McDonough B, Conner L, Adler D, Weinfeld M, O'Gara P, Rehm HL, Machini K, Lebo M, Blout C, Green RC, MacRae CA, Seidman CE, Ho CY; MedSeq Project*. A Comparison of Whole Genome Sequencing to Multigene Panel Testing in Hypertrophic Cardiomyopathy Patients. Circ Cardiovasc Genet. 2017 Oct;10(5):e001768. doi: 10.1161/CIRCGENETICS.117.001768. PubMed 29030401 ↗
Vassy JL, Christensen KD, Schonman EF, Blout CL, Robinson JO, Krier JB, Diamond PM, Lebo M, Machini K, Azzariti DR, Dukhovny D, Bates DW, MacRae CA, Murray MF, Rehm HL, McGuire AL, Green RC; MedSeq Project. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27;167(3):159-169. doi: 10.7326/M17-0188. Print 2017 Aug 1. PubMed 28654958 ↗

Study documents

Protocol and statistical analysis plan · Jan 25, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01736566
Lead sponsor: Brigham and Women's Hospital
Collaborators: National Human Genome Research Institute (NHGRI), Baylor College of Medicine, Duke University
Responsible party: Robert C. Green, MD, MPH (Principal Investigator, The MedSeq Project, Brigham and Women's Hospital) — Principal investigator
First posted: Nov 29, 2012
Start date: Dec 2011
Primary completion: Nov 4, 2016
Completion: Jan 2, 2021
Results posted: Nov 7, 2018
Last update: Aug 27, 2024

Study contacts

Robert C Green, MD, MPH

principal investigator · Brigham and Women's Hospital

Oversight

Data monitoring committee: Yes

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