Clinical implementation of pharmacogenomics via a health system-wide research biobank: the University of Colorado experience

Abstract

In recent years, the genomics community has witnessed the growth of large research biobanks, which collect DNA samples for research purposes. Depending on how and where the samples are genotyped, biobanks also offer the potential opportunity to return actionable genomic results to the clinical setting. We developed a preemptive clinical pharmacogenomic implementation initiative via a health system-wide research biobank at the University of Colorado. Here, we describe how preemptive return of clinical pharmacogenomic results via a research biobank is feasible, particularly when coupled with strong institutional support to maximize the impact and efficiency of biobank resources, a multidisciplinary implementation team, automated clinical decision support tools, and proactive strategies to engage stakeholders early in the clinical decision support tool development process.

Keywords: biobank; implementation; personalized medicine; pharmacogenetics; pharmacogenomics; precision medicine.

Figure 1.. Schematic of the Colorado Center for Personalized Medicine Biobank Research Study.

This schematic illustrates the components of the Colorado Center for Personalized Medicine Biobank Research Study, as explained to potential participants. Participants sign an electronic research consent form through ‘My Health Connection,’ the online UCHealth patient portal. This triggers an order to collect a dedicated biospecimen for future research at the patient's next routine blood draw. Samples are sent to the CLIA-certified Biobank Laboratory, where DNA is extracted and genotyped. When clinical genetic test results are available, participants are sent an electronic secondary clinical consent form through their online patient portal asking permission to return these results to the EHR. Pharmacogenomic results are the first type of clinical genetic test results being preemptively returned to the EHR for this initiative. Permission for use of this figure granted by Kathleen Barnes. CLIA: Clinical Laboratory Improvement Amendments; EHR: Electronic health record.

Figure 2.. Pharmacogenomics Implementation Committee Colorado working groups and associated activities.

This schematic describes the six working groups, which carry out the activities of PICColo. EHR: Electronic health record; IT: Information technology; MEGA: Multi-ethnic genotyping array; PGx: Pharmacogenomics; PICColo: Pharmacogenomics Implementation Committee Colorado.

Figure 3.. Pharmacogenomics Implementation Committee Colorado systematic drug–gene pair development process.

This figure describes the four steps that PICColo uses to develop new drug–gene pairs for implementation. The arrows on the right highlight the iterative nature of this process. CDS: Clinical decision support; PICColo: Pharmacogenomics Implementation Committee Colorado.

Figure 4.. Representative interruptive clinical decision support alert for clopidogrel-CYP2C19 at UCHealth.

The clinical decision support alert notifies a prescribing clinician when they order clopidogrel in the inpatient setting for a patient who is a genetically mediated CYP2C19 intermediate or poor metabolizer and has had a documented percutaneous coronary intervention within the past year. In this example, the patient is a CYP2C19 poor metabolizer (*2/*2 genotype). The clinical decision support alert provides an actionable recommendation to change the medication order, displays pertinent information to endorse the recommendation (e.g., link to references), and provides acknowledge reason options if the clinician chooses not to follow the recommendation. BMT: Bone marrow transplant; CPIC: Clinical Pharmacogenetics Implementation Consortium.

Figure 5.. Timeline of Pharmacogenomics Implementation Committee Colorado clinical decision support implementation.

Over approximately 18 months, the PICColo team designed and deployed pharmacogenomic CDS tools for nine drug–gene pairs (some in progress) across multiple specialties, geographic regions, and care settings in the UCHealth system. CDS: Clinical decision support; PCI: Percutaneous coronary intervention; IP: Inpatient; NSAID: Nonsteroidal anti-inflammatory drugs (includes celecoxib, meloxicam, ibuprofen and piroxicam); OP: Outpatient; PICColo: Pharmacogenomics Implementation Committee Colorado. Reprinted with permission, © 2019 Epic Systems Corporation.