A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare
|Healthy Adults (Full Study and Extension Phase) Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy||Other: Main Study Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report) Other: Placebo Comparator: "Standard of Care" Only|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
|Official Title:||The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine|
- 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 >14 on the anxiety subscale or >16 on the depression subscale 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.
- 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 ]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.
- 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.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Experimental: "Standard of Care" + Whole Genome Sequencing
Doctors and their patients will receive a Genome Report and an Annotated Family History Report.
Other: Main Study 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:
Extension Phase: Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report)
*In the main study participants are are randomized between Experimental and Placebo, in the Extension phase of the study participants all are in the Experimental Arm.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01736566
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Robert C Green, MD, MPH||Brigham and Women's Hospital|