The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine

Abstract

BackgroundWhole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.Methods/DesignThis pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients’ genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results.DiscussionThe impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.Trial registrationClinicalTrials.gov identifier NCT01736566

The role of high performance, grid and cloud computing in high-throughput sequencing

“…HTS has been applied to varied applications (Table I) from understanding the role of noncoding sequence variants in cancer [7], identifying genomic targets of small molecules [8] to the reconstruction of ancient genomes and epigenomes [9]. [10].…”

Returning pharmacogenetic secondary findings from genome sequencing: let’s not put the cart before the horse

“…DNA sequencing was introduced to enable the molecular diagnosis of congenital disorders and rare syndromes, followed by several studies that explored the introduction of sequencing in various clinical settings. 1,2 Given the role of DNA in many diseases and outcomes, it is understandable that there is research interest in the secondary use of sequencing data and in the preemptive sequencing of healthy individuals in the event that DNA data are needed for a later medical decision.…”

Have You Met GINA?

“…For example, those enrolled in the randomized trial, the MedSeq Project, have their wholegenome sequencing stored in their electronic medical record and their outcomes are tracked. 7 Twenty-five percent of subjects who declined to participate voiced concerns regarding fear of discrimination of health Disclosure: The author has disclosed that she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article.…”