Brigham and Women's Hospital CERT-Leveraged Project: Placing Genetic Information at Physicians' Fingertips

By Shelley Norden Barnes

The field of genetic testing is evolving rapidly, making it difficult for health care providers to stay current about the many genetic variants of each inherited disease. Recently, members of the Brigham & Women’s Hospital (BWH) Center for Education and Research on Therapeutics (CERT) collaborated on a study evaluating a breakthrough software tool that places a patient’s genetic information directly at the physician’s fingertips. And based on feedback from the physician-participants, the tool is helping to optimize the care of patients at risk of an inherited disease.

Insight Into Our Genetic Makeup

The study, whose findings were published in October 2012 in the Journal of Biomedical Informatics, evaluated GeneInsight Suite, a software package that provides timely updates on genetic variants to clinicians. Funded by the National Institutes of Health, the study research team consisted of geneticists, software analysts, information system developers, and quality assurance and patient safety experts from BWH, Partners HealthCare Center for Personalized Genetic Medicine in Cambridge, and Harvard Medical School. BWH CERT researcher David Bates, M.D., M.Sc., and Lynn Volk, M.H.S., lead the study.

"We focused on hypertrophic cardiomyopathy and its genetic variants," says Bates, principal investigator of the BWH CERT. "Everyone has many genetic variations in their genome. For most inherited conditions, one individual may have hundreds of DNA changes. The significance of them is not always known, but new scientific evidence is constantly emerging, making it difficult for physicians to keep up with all these variants and how they affect individual patients."

Inherited as an autosomal dominant trait, familial hypertrophic cardiomyopathy is attributed to mutations in one of several genes known to encode sarcomere proteins in cardiac muscle. Because of the different genes involved, many genetic variants of the disease are possible. Within the first 6 years alone, the Laboratory for Molecular Medicine (LMM), directed by Heidi Rehm, Ph.D., at the Partners HealthCare Center for Personalized Genetic Medicine (PCPGM) changed the disease-status category of approximately 214 previously reported gene variants associated with hypertrophic cardiomyopathy, affecting nearly 756 of their patients with only that single condition.

"The GeneInsight Suite reduces the complexity of tracking and interpreting this information by sending providers updates on a patient’s genetic test results to reflect relevant status changes to specific genetic variants, changes that directly impact patient care," Bates explains. Having more detailed genetic data helps providers determine whether or not a patient is at risk for a specific gene-based disease such as hypertrophic cardiomyopathy, and they can work with the patient to plan a screening schedule and course of action based on that patient’s genetic risk.

"Physicians feel they are leaps ahead having this information pushed out to them in a format that’s easily digestible and provides critical genetic information," says Volk, associate director of the Clinical and Quality Analysis Department within the Partners HealthCare system's Information Services. "They can access the original genetic test reports, amended reports, and the variant change information, which includes a summary of the evidence supporting the decision to change the variant classification." The beauty of it, she adds, is that the laboratory automatically sends out alerts about significant variant changes and updates the application, allowing providers to log into the system at any time and see the current genetic profile of any patient.

Genetic Screening: A Crystal Ball?

The importance of genetic profiles cannot be overstated, as many life-threatening diseases are inheritable and can be passed from parents to children. Hypertrophic cardiomyopathy, for example, is the most common genetic cardiovascular disease, with a prevalence of approximately 1 in 500 in the general population. A parent carrying a disease-causing mutation of a gene associated with hypertrophic cardiomyopathy has a 50-percent chance of transmitting the mutation to his or her child, a statistic that underscores the need for genetic testing in potentially at-risk family members who are asymptomatic and regular screenings for any family member who tests positive for a mutation.

"This information is critical to genetic decision support, since providers use it to counsel patients and explain what to expect and what their family members can expect," says Bates. "New knowledge about genetic variants may critically influence the treatment of patients and their families." In fact, provider feedback during the study confirmed that the software tool had the most impact on decisions  that surround the use of genetic testing for managing the care of families at risk for hypertrophic cardiomyopathy.

A Provider-Driven Process

The utility of the GeneInsight Suite is a direct reflection of provider input from two phases of the study. The first was a small usability assessment during which users were encouraged to "think aloud" and share their experiences as they used the software tool; this process allowed developers to enhance the application's effectiveness before it underwent broader testing. The next phase was conducted at two academic medical centers and genetics clinics with physicians, genetic counselors, and nurses who ordered significant numbers of genetic tests for hypertrophic cardiomyopathy.

"These clinics were getting hypertrophic cardiomyopathy tests done at our laboratory," Volk explains. "They’d been receiving test results from the LMM as part of their practice, so the LMM contacted these providers about their interest in participating in the study."

The GeneInsight Suite, developed by the LMM and PCPGM under the direction of Samuel Aronson, provides the information technology infrastructure to capture and store electronic genetic reports and generate physician alerts when new variant knowledge is identified by the laboratory. GeneInsight captures key information related to a patients' genetic testing process. Periodically geneticists in the lab will learn about, or discover, new data on a variant that has been reported before and will change the classification of the variant. When new data emerges the laboratory evaluates if there is sufficient evidence to change a variant’s classification. Once a new classification is approved by a geneticist, treating clinicians are alerted so they have that information available at the point of care.

Throughout the usability study, researchers compiled feedback from physician-participants to make modifications that simplified the user experience and addressed provider needs. The study not only helped refine the software tool, but it made a lasting impression on its participants.

A Pathway to Personalized Medicine

"The GeneInsight database is at the core of personalized medicine," claims Calum MacRae, M.D., Ph.D., who has been involved in the study since its inception. "With genetic information, you’re building a picture of the individual: you have a framework for that person but you don’t know how to predict disease in the rest of the family. This tool fits beautifully into the doctor-patient relationship both by managing the family’s genetic data and by helping us understand how the classification of their mutation changes over time."

A cardiologist and geneticist in the BWH Cardiovascular Genetics Program, MacRae operates on both sides of the genetic spectrum, both as a research scientist and as a practicing physician.

"I’ve used other systems, but the GeneInsight database dramatically changes what’s feasible," he continues. "The genetic picture is continually being reinterpreted as new information comes to the table, so it’s a dynamic relationship that’s built into the software. It’s a new way to manage the flow of information from the doctor to the patient. With this new information, we’re forced to reappraise everything we knew about a patient from a genetic perspective." This, MacRae emphasizes, demonstrates how the clinical and genetic interpretations are intricately linked: if the variant is reinterpreted, then the clinical approach may need to be revised as well.

"Testing a person’s DNA structure isn’t like testing for cholesterol or blood pressure, which can change from test to test," MacRae explains. "DNA is a fixed point, and the initial test stays the same over time. It’s the interpretation of the variants that is constantly changing, such that a 'wait and see' situation may be clinically actionable in as few as 6 weeks as new variant updates are released."

Rigorous Clinical Decision Support

Before GeneInsight Suite was launched, health care providers had to track any changes in the variants of mutated genes themselves or request that the laboratory review the medical evidence to determine any changes in the status of variants.

"Laboratories would suggest physicians call back in a year or so to see if any new information was available," Volk stresses. "Then, if the status of a genetic variant in a given patient changed, there wasn’t a systematic way to make sure that other doctors of patients with the same variant were notified."

In short, says Bates, GeneInsight automates an increasingly challenging process and reduces the mental stress in tracking complex genetic information for every patient.

"Having the tool directly at the point of care has made it vastly easier to care for patients," Bates sums up. "This is clinical decision support in its most rigorous form."

The Centers for Education and Research on Therapeutics (CERTs) are a nationwide network of six research centers and a coordinating center that receive core financial support from the Agency for Healthcare Research and Quality. The CERTs conduct research and provide education that will advance the optimal use of drugs, medical devices, and biological products; increase awareness of the benefits and risks of therapeutics; and improve quality while cutting the costs of health care.

Partners HealthCare licensed the GeneInsight technology in November 2012, to a company in which it acquired 100% equity ownership.  This transaction was reviewed by the Partners Committee on Conflicts of Interest in light of Partners acquisition of this financial interest, and the Committee, consistent with Partners policy, required that notice of Partners financial interest in the technology be provided to journals and in publications and presentations on the technology.

To read more about the study, view the abstract at: http://www.ncbi.nlm.nih.gov/pubmed/22521718

To learn more about the GeneInsight Suite tool, contact:

Michael A. Band
Partners Research Ventures and Licensing
617-954-9738
mband@partners.org

Return to Featured CERTs Research