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

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ClinicalTrials.gov Identifier: NCT01736566
Recruitment Status : Active, not recruiting
First Posted : November 29, 2012
Results First Posted : November 7, 2018
Last Update Posted : December 4, 2018
Sponsor:
Collaborators:
National Human Genome Research Institute (NHGRI)
Baylor College of Medicine
Duke University
Information provided by (Responsible Party):
Robert C. Green, MD, MPH, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE August 17, 2012
First Posted Date  ICMJE November 29, 2012
Results First Submitted Date  ICMJE July 27, 2018
Results First Posted Date  ICMJE November 7, 2018
Last Update Posted Date December 4, 2018
Actual Study Start Date  ICMJE December 2011
Actual Primary Completion Date November 4, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 10, 2018)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
  • Change in Attitudes and Trust [ Time Frame: Baseline and 6-weeks post-disclosure ]
    Novel measures and adapted measures (Hall, MA, et al. 2006) will assess participants' attitudes toward genetic information and trust of their physicians and the medical system regarding interpretation and use of genetic information.
  • Change in Self Efficacy [ Time Frame: Baseline and 6-months post-disclosure ]
    Assessed through a scale developed for the Multiplex Initiative (Kaphingst, K.A., et al. 2012)
  • Change in Preferences for WGS Information [ Time Frame: Baseline and 6-weeks post-disclosure ]
    Through novel survey items, participants will be asked about their preferences for the types of genetic testing results they would like to receive from their whole genome sequence and their preferences regarding their sequencing results in their medical record.
  • Change in Risk Perception [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure) and 6-months post-disclosure ]
    Novel and adapted survey measures from the Multiplex Initiative will assess changes in how participants perceive their own health and risk of health conditions.
  • Change in Shared Decision Making [ Time Frame: Baseline ]
    Changes in shared decision making will be assessed through the Control Preferences Scale, a validated survey measure designed to ascertain the degree of control an individual wants to assume when decisions are being made about medical treatment. The measure will assess how patients prefer to make healthcare decisions with their doctor. This will be measured one time as a stable trait.
  • Change in Intolerance of Uncertainty [ Time Frame: Baseline and 6-months post-disclosure ]
    Changes in participants' tolerance for uncertainty will be assessed through a short version of the Intolerance of Uncertainty Scale (Carleton, 2007).
  • Change in General Anxiety and Depression [ Time Frame: Baseline and at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    The Hospital Anxiety and Depression Scale (HADS) scale will be administered through a survey. This is a validated scale designed to assess the participants' level of depression and anxiety through Likert-type questions. Any participant scoring 11 or higher will be contacted by study staff for evaluation.
  • Change in Health Behaviors and Intentions [ Time Frame: Baseline and at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    Changes in participants' health behaviors and intentions will be assessed through novel and adapted survey measures (from the Cancer Prevention Research Center, Stages of Change Measures, 1991) asking about vitamin, supplement and medication use, insurance-purchasing behaviors, and diet, smoking and exercise practices.
  • Change in Information Seeking and Sharing [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    Changes in participants' information seeking and sharing behaviors will be assessed through measures adapted from the HINTS surveys on information seeking and information sharing.
  • Changes in Genetic Literacy and Numeracy [ Time Frame: Assessing Genomic Literacy at baseline and 6-months post-disclosure. Measuring Subjective Numeracy at baseline and Objective Numeracy at post-disclosure visit (about 1 hour after results disclosure) ]
    Changes in participants' numeracy will be assessed through validated measures of objective and subjective numeracy (Lipkus et al. 2007 and Fagerlin et al. 2007), and changes in genetic literacy will be measured by survey measures adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012). We are only assessing changes in Genetic Literacy. Genetic Numeracy will be measured one time as a stable trait.
  • Changes in Health Care Utilization [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure, and 6-months post-disclosure ]
    Changes in participants' health care utilization will be assessed through novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS).
  • Change in Expectations/Perceived Utility [ Time Frame: At baseline, disclosure visit at the disclosure visit (about 1 hour after results disclosure), 6-weeks and 6-months post-disclosure ]
    Novel survey items will assess participants' expectations of the number of health conditions they will learn about through genome sequencing, and their interest in, their perceived usefulness of and their concerns about these results. Novel survey items will also assess affective forecasting. Additionally, novel survey items will assess participants' perceived utility of their results in terms of their own healthcare and planned behavior.
Change History Complete list of historical versions of study NCT01736566 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2018)
  • 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) ]
    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.
  • 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) ]
    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.
  • 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) ]
    A novel item assessed participants' subjective understanding of their study results on a 1-5 scale, where higher scores indicate greater subjective understanding.
  • Expectations [ Time Frame: Baseline ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
  • Psychological Impact [ Time Frame: 6-weeks post-disclosure and 6-months post-disclosure ]
    Psychological impact will be assessed by a modified version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire.
  • Satisfaction and Decisional Regret [ Time Frame: Assessing Satisfaction with Clinician and Decisional Regret at post-disclosure visit (about 1 hour after results disclosure). Assessing Satisfaction with Information at 6-weeks post-disclosure. ]
    Participants' satisfaction with their clinician will be measured via the RIAS scale (Roter and Larson, 2002). Participants' satisfaction with the information learned from genome sequencing will be assessed with novel measures. Decisional regret will be assessed through a validated scale (Brehaut 2003).
  • Understanding and Recall [ Time Frame: Assessing Understanding of Informed Consent at baseline. Assessing Understanding of Results at post-disclosure visit at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure, and 6-months post-disclosure ]
    Novel items will assess participants' understanding of their genome sequencing results. Additionally, novel items will assess participants' objective understanding of the informed consent for whole genome sequencing and adapted items will assess participants' subjective understanding of the informed consent for genome sequencing.
  • Motivations for Participation [ Time Frame: Baseline ]
    Novel survey items will ask participants about why they decided to participate in this study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare
Official Title  ICMJE The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Healthy Adults (Full Study and Extension Phase)
  • Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy
Intervention  ICMJE
  • Other: Family 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.

  • Other: Family History Only
    Doctors and their patients receive a Family History report.
Study Arms  ICMJE
  • Experimental: Family History + Whole Genome Sequencing
    Doctors and their patients receive a Genome Report and an Annotated Family History Report.
    Intervention: Other: Family History + Whole Genome Sequencing
  • Active Comparator: Family History Only
    Doctors and their patients receive an Annotated Family History Report only.
    Intervention: Other: Family History Only
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 10, 2018)
213
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2012)
200
Estimated Study Completion Date  ICMJE August 28, 2022
Actual Primary Completion Date November 4, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01736566
Other Study ID Numbers  ICMJE MedSeq™
U01HG006500 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert C. Green, MD, MPH, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE
  • National Human Genome Research Institute (NHGRI)
  • Baylor College of Medicine
  • Duke University
Investigators  ICMJE
Principal Investigator: Robert C Green, MD, MPH Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP