Practicing Pharmacogenomics at Scale

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Original photo by Piotrus, edited/uploaded by Crazypaco at English Wikipedia [CC BY-SA 2.5 (], via Wikimedia Commons

A cardiac patient at UPMC Presbyterian in Pittsburgh is fortunate to be where she is. Her doctors prescribed a blood thinner based on her pharmacogenetic profile, and this significantly increases the likelihood the drug will work for her.

As both a world-renowned healthcare provider and insurer, UPMC is uniquely positioned to deliver on the goal of making healthcare both better and more cost-effective. This is particularly true of its work in precision medicine and pharmacogenomics, where clinicians use data to inform clinical decisions that help improve patient outcomes while driving efficiencies across the entire system.

Dr. Philip Empey, a faculty member in the University of Pittsburgh School of Pharmacy, is among a vanguard in healthcare who is proving how pharmacogenomics can be used in the clinical setting. His multidisciplinary team at the University of Pittsburgh helped launch PreCISE-Rx (Pharmacogenomics-guided Care to Improve the Safety and Effectiveness of Medications), an initiative that is now driving clinical decision-making at hospitals such as UPMC Presbyterian.

Dr. Empey describes PreCISE-Rx as a pharmacogenomics implementation and research program that enables “precision prescribing.” The prescribing is based on CLIA-lab based testing and the return of results to electronic health records along with recommendations that help clinicians select the optimal drug therapy.

The first implementation of PreCISE-Rx is routine, standard-of-care testing for CYP2C19 variants, which, if present, suggest a patient is less able to metabolize clopidogrel, a medication commonly prescribed after stenting cardiac catheterization patients. Those who test positive for CYP2C19 variants would receive an alternative therapy. The benefits of this pharmacogenomics test are obvious: a more precise and cost-effective intervention and, most important, a better outcome for patients.

Joining Dr. Empey in the effort to show how pharmacogenomics can advance precision medicine is Dr. Oscar Marroquin, a cardiologist and chief clinical analytics officer at UPMC. As a practicing physician, he sees value not only for his patients but also in the wealth of data generated. “Our focus to date at UPMC has been all about the phenotype; we feel that successfully consuming our electronic health record data lays the foundation on which to link genomic data so that we can do precision medicine at scale.”

The precision medicine initiatives underway at UPMC and the University of Pittsburgh aren’t static with respect to new data sources. Dr. Marroquin says that massive amounts of data from across the UPMC system, and presumably outside as well, will improve clinical decision-making once aggregated and systematically analyzed to deliver actionable, patient-specific insights at the point of care.

To bring more data to the table, the UPMC/University of Pittsburgh partnership recently expanded to include Thermo Fisher Scientific. The three organizations recently launched a new Pharmacogenomics (PGx) Center of Excellence to bring together genomic, bioinformatic and pharmacogenomic technology and expertise. The center focuses on the discovery and validation of medication response predictors in patients, relying on Thermo Fisher’s PGx testing technology for an “at-scale” preemptive, panel-based PGx testing study that will include up to 150,000 patients in Western Pennsylvania. It will also immediately leverage a new University of Pittsburgh institutional bio-repository, Pitt+Me Discovery, developed by the Clinical and Translational Science Institute (CTSI) to rapidly scale precision medicine research.

The study includes high-density population screening of 4,627 markers within 1,191 genes to isolate concise PGx signatures that associate with novel and known phenotypes within specific patient populations. This will support the larger effort to show that targeted PGx testing can be deployed clinically in the future, and at scale, using validated testing platforms.

The other focus for the PGx Center of Excellence is helping to overcome clinical implementation barriers and showing the clinical utility and economic value of widespread PGx testing. During a recent panel at the American Association for the Advancement of Science (AAAS) Annual Meeting in Austin, Texas, Drs. Marroquin and Empey joined Dr. Betty Woo from Thermo Fisher to discuss ways to overcome barriers and accelerate adoption.

Consensus on the AAAS panel was that uncertainty around reimbursement for PGx testing remains a significant obstacle. But UPMC is both a healthcare provider and health plan, and this makes for a unique proving ground for quantifying the economic benefits of at scale pharmacogenomics. What’s more, the panelists agreed that their Pittsburgh collaboration can be a model for aligning people, processes and technology in ways that benefit patients, health systems and payers elsewhere in the U.S., if not globally.

How widespread will pharmacogenomics be in five years? Dr. Empey believes that preemptive panel-based testing will be deployed across more populations and that “leading institutions and academia-industry partnerships will use big data and analytics to build risk models based on projected outcomes, medication-use data and genetic data to achieve optimal population health through better medication outcomes.”

Dr. Marroquin agrees: “We’re eager to expand the PreCISE-Rx program beyond cardiology, and we envision that pharmacogenomics will soon be widely used in everyday decision-making across UPMC and at other leading health systems around the world.”