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

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Baylor College of Medicine
Duke University
Information provided by (Responsible Party):
Robert C. Green, MD, MPH, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01736566
First received: August 17, 2012
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

The MedSeq™ Project seeks to explore the impact of incorporating information from a patient's whole genome sequence into the practice of clinical medicine.


Condition Intervention
Healthy Adults
Hypertrophic Cardiomyopathy
Other: Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report)
Other: Placebo Comparator: "Standard of Care" Only

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Change in Attitudes and Trust [ Time Frame: Baseline and 6-weeks post-disclosure ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.

  • Change 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Psychological Impact [ Time Frame: 6-weeks post-disclosure and 6-months post-disclosure ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Novel survey items will ask participants about why they decided to participate in this study.


Estimated Enrollment: 200
Study Start Date: December 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: "Standard of Care" + Whole Genome Sequencing
Doctors and their patients will receive a Genome Report and an Annotated Family History Report.
Other: Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report)

Doctors and their patients will receive a Genome Report and a Family History Report.

There will be two sections of the Genome Report:

  1. The General Genome Report, which will include highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations.
  2. The Cardiac Risk Report, which will 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.
Placebo Comparator: "Standard of Care" Only
Doctors and their patients will receive an Annotated Family History Report only.
Other: Placebo Comparator: "Standard of Care" Only
Doctors and their patients will receive a Family History report only

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) 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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) and a family history of HCM who previously had or who are candidates for targeted HCM 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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736566

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Baylor College of Medicine
Duke University
Investigators
Principal Investigator: Robert C Green, MD, MPH Brigham and Women's Hospital
  More Information

Additional Information:
NHGRI  This link exits the ClinicalTrials.gov site

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert C. Green, MD, MPH, Principal Investigator, The MedSeq Project, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01736566     History of Changes
Other Study ID Numbers: MedSeq™, U01HG006500
Study First Received: August 17, 2012
Last Updated: November 28, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Primary Care
Cardiology
Hypertrophic Cardiomyopathy
Whole Genome Sequencing

Additional relevant MeSH terms:
Cardiomyopathy, Hypertrophic
Hypertrophy
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on August 21, 2014