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

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.