Healthy Adults (Full Study and Extension Phase)NCT01736566

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

A study testing Family History + Whole Genome Sequencing and Family History Only in people with Healthy Adults (Full Study and Extension Phase) and Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 90 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Adults (Full Study and Extension Phase), Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy
What is being tested?: Family History + Whole Genome Sequencing and Family History Only
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 213 participants
Where: 1 siteUnited States
Study dates: Dec 2011to 2 Jan 2021
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.
Part 2:
MedSeq participants determined to have a monogenic finding

Who cannot join

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:

Show all 9Show fewer

Above inclusion and exclusion criteria PLUS:
Participants not previously enrolled in MedSeq Project
Participants not identified to have a monogenic finding

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine

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: Healthy Adults (Full Study and Extension Phase), Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy
Being tested: Family History + Whole Genome Sequencing, Family History Only
Keywords: Primary Care, Cardiology, Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Whole Genome Sequencing
Medical subject headings: Cardiomyopathy, Hypertrophic, Cardiomyopathy, Dilated

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Family History + Whole Genome SequencingOther
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.
Family History OnlyOther
Doctors and their patients receive a Family History report.

Study groups in NCT01736566
Study group	Role	What they receive
Family History + Whole Genome Sequencing	Experimental	Doctors and their patients receive a Genome Report and an Annotated Family History Report. Receives: Other: Family History + Whole Genome Sequencing
Family History Only	Active comparator	Doctors and their patients receive an Annotated Family History Report only. Receives: Other: Family History Only

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 20112 Jan 2021

First posted29 Nov 2012 (estimated)
Study startDec 2011
Primary completion4 Nov 2016
Study completion2 Jan 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (35)Papers the sponsor has linked to this study.
Other trials for Healthy Adults (Full Study and Extension Phase)Studies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Health services research
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 213 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01736566
Sponsor's protocol ID: MedSeq™
Other IDs: U01HG006500
Status last verified: Aug 2024
First submitted: 17 Aug 2012
Last updated: 27 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Biesecker LG. Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project. Genet Med. 2012 Apr;14(4):393-8. doi: 10.1038/gim.2011.78. Epub 2012 Feb 16.
PubMed 22344227
Green ED, Guyer MS; National Human Genome Research Institute. Charting a course for genomic medicine from base pairs to bedside. Nature. 2011 Feb 10;470(7333):204-13. doi: 10.1038/nature09764.
PubMed 21307933
Kohane IS, Masys DR, Altman RB. The incidentalome: a threat to genomic medicine. JAMA. 2006 Jul 12;296(2):212-5. doi: 10.1001/jama.296.2.212. No abstract available.
PubMed 16835427
Khoury MJ, Berg A, Coates R, Evans J, Teutsch SM, Bradley LA. The evidence dilemma in genomic medicine. Health Aff (Millwood). 2008 Nov-Dec;27(6):1600-11. doi: 10.1377/hlthaff.27.6.1600.
PubMed 18997217
Varmus H. Ten years on--the human genome and medicine. N Engl J Med. 2010 May 27;362(21):2028-9. doi: 10.1056/NEJMe0911933. No abstract available.
PubMed 20505183
Evans JP, Meslin EM, Marteau TM, Caulfield T. Genomics. Deflating the genomic bubble. Science. 2011 Feb 18;331(6019):861-2. doi: 10.1126/science.1198039. No abstract available.
PubMed 21330519
Hall MA, Camacho F, Lawlor JS, Depuy V, Sugarman J, Weinfurt K. Measuring trust in medical researchers. Med Care. 2006 Nov;44(11):1048-53. doi: 10.1097/01.mlr.0000228023.37087.cb.
PubMed 17063137
Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.
PubMed 22694298
Carleton RN, Norton MA, Asmundson GJ. Fearing the unknown: a short version of the Intolerance of Uncertainty Scale. J Anxiety Disord. 2007;21(1):105-17. doi: 10.1016/j.janxdis.2006.03.014. Epub 2006 May 2.
PubMed 16647833
Lipkus IM. Numeric, verbal, and visual formats of conveying health risks: suggested best practices and future recommendations. Med Decis Making. 2007 Sep-Oct;27(5):696-713. doi: 10.1177/0272989X07307271. Epub 2007 Sep 14.
PubMed 17873259
Fagerlin A, Zikmund-Fisher BJ, Ubel PA, Jankovic A, Derry HA, Smith DM. Measuring numeracy without a math test: development of the Subjective Numeracy Scale. Med Decis Making. 2007 Sep-Oct;27(5):672-80. doi: 10.1177/0272989X07304449. Epub 2007 Jul 19.
PubMed 17641137
Roter D, Larson S. The Roter interaction analysis system (RIAS): utility and flexibility for analysis of medical interactions. Patient Educ Couns. 2002 Apr;46(4):243-51. doi: 10.1016/s0738-3991(02)00012-5.
PubMed 11932123
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

Study at a glance

From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine
ClinicalTrials.gov ID: NCT01736566
Acronym / sponsor ID: MedSeq™
Conditions: Healthy Adults (Full Study and Extension Phase), Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy
Keywords: Primary Care, Cardiology, Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Whole Genome Sequencing
Study type: Interventional
Recruitment status: Completed
Enrolment: 213 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: National Human Genome Research Institute (NHGRI), Baylor College of Medicine, Duke University
Study start: Dec 2011 (actual)
Primary completion: 4 Nov 2016 (actual)
Study completion: 2 Jan 2021 (actual)
First posted: 29 Nov 2012 (estimated)
Results: Posted 7 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Health services research
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Family History + Whole Genome Sequencing	Experimental	Other: Family History + Whole Genome SequencingDoctors and their patients receive a Genome Report and an Annotated Family History Report.
Family History Only	Active comparator	Other: Family History OnlyDoctors and their patients receive an Annotated Family History Report only.

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.
MedSeq participants determined to have a monogenic finding

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Family History + Whole Genome SequencingDoctors 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.	Other	Family History + Whole Genome Sequencing
Family History OnlyDoctors and their patients receive a Family History report.	Other	Family History Only

Primary outcome

Change in Attitudes and Trust
Time frame: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline
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.
Change in Self Efficacy
Time frame: Baseline and 6-months post-results disclosure (6 mos. follow-up administered approx. 17 months after baseline)
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.
Change in Preferences for WGS Information
Time frame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
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.
Change in Perceived Health
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)
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
Change in Shared Decision Making
Time frame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
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.
Change in Intolerance of Uncertainty
Time frame: Baseline and 6-months post-disclosure (6 mos. follow-up administered approx. 17 mos. after baseline)
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.
Change in General Anxiety and Depression
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)
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.
Change in Health Behaviors
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)
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.
Information Sharing
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)
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).
Changes in Genomic Literacy
Time frame: Assessing Genomic Literacy at baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
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.
Changes in Health Care Utilization
Time frame: 6 months prior to disclosure and 6-months post-disclosure (approx. 17 mos. after baseline) and 5-years post-disclosure
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.
Change in Perceived Utility
Time frame: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
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.

4 secondary outcomes

Psychological Impact
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
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
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
Time frame: Baseline

Results and safety

Results posted to the registry on 7 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Family History + Whole Genome Sequencing: Primary Care	51	50
Family History Only: Primary Care	50	50
Family History + Whole Genome Sequencing: Cardiology	50	49
Family History Only: Cardiology	52	51
Extension Cohort	10	6

Primary outcome: Change in Attitudes and Trust

Time frame: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline. Mean (Standard Deviation). Unit: units on a scale

Measure	Family History + Whole Genome Sequencing: Primary Care n = 50	Family History Only: Primary Care n = 44	Family History + Whole Genome Sequencing - Cardiology n = 48	Family History Only: Cardiology n = 46	Extension Cohort n = 6
Value	0.0 (5.3)	0.7 (4.5)	3.5 (5.1)	1.8 (3.5)	1.0 (6.3)

Population analysed: Participants who completed the baseline survey and 6 week follow-up survey

Primary outcome: Change in Self Efficacy

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

Measure	Family History + Whole Genome Sequencing: Primary Care n = 49	Family History + Whole Genome Sequencing - Cardiology n = 47	Extension Cohort n = 7
Value	0.3 (3.4)	0.5 (4.3)	3.1 (5.7)

Population analysed: Participants randomized to the experimental Family History + Whole Genome Sequencing arm who completed both the baseline and the 6-month follow-up surveys

Primary outcome: Change in Preferences for WGS Information

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

Measure	Family History + Whole Genome Sequencing: Primary Care n = 48	Family History Only: Primary Care n = 42	Family History + Whole Genome Sequencing - Cardiology n = 47	Family History Only: Cardiology n = 44	Extension Cohort n = 6
Value	-.1 (1.5)	0.2 (2.1)	0 (2.0)	.4 (2.3)	0.0 (1.9)

Population analysed: Participants who completed both the baseline and 6-week follow-up surveys

Primary outcome: Change in Perceived Health

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). Mean (Standard Deviation). Unit: units on a scale

Measure	Family History + Whole Genome Sequencing: Primary Care n = 50	Family History Only: Primary Care n = 49	Family History + Whole Genome Sequencing: Cardiology n = 49	Family History Only: Cardiology n = 51	Extension Cohort n = 8
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)

Population analysed: Participants who completed the item on patient surveys.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Family History + Whole Genome Sequencing: Primary Care	0 of 51 (0%)	0 of 51 (0%)	0 of 51
Family History Only: Primary Care	0 of 50 (0%)	3 of 50 (6%)	0 of 50
Family History + Whole Genome Sequencing: Cardiology	3 of 50 (6%)	0 of 50 (0%)	3 of 50
Family History Only: Cardiology	1 of 52 (1.9%)	0 of 52 (0%)	1 of 52
Extension Cohort	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22344227Biesecker LG. Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project. Genet Med. 2012 Apr;14(4):393-8. doi: 10.1038/gim.2011.78. Epub 2012 Feb 16.
Background: PubMed 21307933Green ED, Guyer MS; National Human Genome Research Institute. Charting a course for genomic medicine from base pairs to bedside. Nature. 2011 Feb 10;470(7333):204-13. doi: 10.1038/nature09764.
Background: PubMed 16835427Kohane IS, Masys DR, Altman RB. The incidentalome: a threat to genomic medicine. JAMA. 2006 Jul 12;296(2):212-5. doi: 10.1001/jama.296.2.212. No abstract available.
Background: PubMed 18997217Khoury MJ, Berg A, Coates R, Evans J, Teutsch SM, Bradley LA. The evidence dilemma in genomic medicine. Health Aff (Millwood). 2008 Nov-Dec;27(6):1600-11. doi: 10.1377/hlthaff.27.6.1600.
Background: PubMed 20505183Varmus H. Ten years on--the human genome and medicine. N Engl J Med. 2010 May 27;362(21):2028-9. doi: 10.1056/NEJMe0911933. No abstract available.
Background: PubMed 21330519Evans JP, Meslin EM, Marteau TM, Caulfield T. Genomics. Deflating the genomic bubble. Science. 2011 Feb 18;331(6019):861-2. doi: 10.1126/science.1198039. No abstract available.
Background: PubMed 17063137Hall MA, Camacho F, Lawlor JS, Depuy V, Sugarman J, Weinfurt K. Measuring trust in medical researchers. Med Care. 2006 Nov;44(11):1048-53. doi: 10.1097/01.mlr.0000228023.37087.cb.
Background: PubMed 22694298Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.
Background: PubMed 16647833Carleton RN, Norton MA, Asmundson GJ. Fearing the unknown: a short version of the Intolerance of Uncertainty Scale. J Anxiety Disord. 2007;21(1):105-17. doi: 10.1016/j.janxdis.2006.03.014. Epub 2006 May 2.
Background: PubMed 17873259Lipkus IM. Numeric, verbal, and visual formats of conveying health risks: suggested best practices and future recommendations. Med Decis Making. 2007 Sep-Oct;27(5):696-713. doi: 10.1177/0272989X07307271. Epub 2007 Sep 14.
Background: PubMed 17641137Fagerlin A, Zikmund-Fisher BJ, Ubel PA, Jankovic A, Derry HA, Smith DM. Measuring numeracy without a math test: development of the Subjective Numeracy Scale. Med Decis Making. 2007 Sep-Oct;27(5):672-80. doi: 10.1177/0272989X07304449. Epub 2007 Jul 19.
Background: PubMed 11932123Roter D, Larson S. The Roter interaction analysis system (RIAS): utility and flexibility for analysis of medical interactions. Patient Educ Couns. 2002 Apr;46(4):243-51. doi: 10.1016/s0738-3991(02)00012-5.
NHGRILink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert C Green, MD, MPH principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Attitudes and Trust (time frame: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01736566, which also lists 35 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2024.