The pace of discovery of potentially actionable pharmacogenomic variants has increased greatly in recent years. However, translation of this knowledge into patient care has been slow. One reason is that successful translation into practice requires many steps. Patients must be willing to consent to the collection and use of genomic information and clinicians must be willing and able to correctly use that information. Pharmacogenomic information must be accessible at the point of care and presented in a way that enables clinical decision- making. Finally, those clinical decisions must improve outcomes. Additional barriers remain, e.g., in in-house genotyping, physician familiarity with pharmacogenomics, and provision of concise recommendations. In this relatively young field, evidence in African Americans is needed to understand the impact of pharmacogenomics to clinical care. Nevertheless, some medical centers have begun to clinically implement pharmacogenomics without consideration for the predictive factors that may affect minority populations.
THE GENOMIC PRESCRIBING SYSTEM
The Genomic Prescribing System (GPS) was developed within the University of Chicago as an innovative tool to address many of these barriers. Patients are preemptively genotyped for clinically relevant single nucleotide polymorphisms (SNPs). The GPS then uses this genotype data to provide the patient’s physician with evidence-based, concise, actionable information (“consults”) when medications affected by these SNPs are prescribed. This approach eliminates the need to order specific genetic tests at the time a drug is prescribed and gives the physician access to the relevant information at the time of prescribing. Initial studies showed the feasibility of GPS integration into the clinical workflow with robust physician acceptance. Another advantage of the GPS is that it can be easily adapted to incorporate race-specific guidance.
THE ROLE OF RACE IN TRANSLATION
The role of race in making pharmacogenomic recommendations is important because the benefit of recommendations for minority patients based on genetic associations found in European ancestry patients is unclear. Population-based studies in African Americans have shown that European-specific SNPs are not always present in African Americans, while African–American specific SNPs, although present, may not be predictive in European populations. As a result, population specific pharmacogenomics recommendations are needed to provide the most accurate genotype-guided therapy. Warfarin is a prime opportunity for translation into race specific pharmacogenomic interventions. Evidence has demonstrated differences by race in the effects of pharmacogenomic prescribing and how to improve prescribing guidance by race. The seminal clinical trials of genotype guided warfarin dosing the European ancestry EU-PACT study, showed clinical benefit to genotype guided warfarin dosing, but the mixed ancestry COAG study did not. Strikingly, the COAG study showed harm to African Americans receiving genotype-guided therapy, raising broad concerns about precision medicine for African Americans. We responded by showing that no African American specific SNPs were included in the genotype guided arm, so many African Americans would have been misclassified. This shows that refining the information provided to clinicians to give race specific recommendations is critical to delivering truly individualized precision medicine to African Americans.
The broad objective of this translational project is to move African American pharmacogenomics from discovery to implementation. We will do this by developing race-specific guidance within the GPS, establishing a large repository of African-American patients with genotype, prescribing information, and outcomes data to support both discovery and translational studies, and investigating how the provision of race specific guidance influences prescribing and therapeutic effectiveness. Warfarin will be used as the first clinical application. We hypothesize that prospectively genotyping and incorporation of African-American specific genetic variants into clinical care will influence physician-prescribing and therapeutic effectiveness.
OUR SPECIFIC AIMS ARE:
AIM 1: Incorporate race-specific SNPs and recommendations into the GPS
AIM 2: Create a cohort of African Americans patients receiving care using the GPS
AIM 3: Assess race-specific recommendations via the GPS in other institutions
Peter H. O’Donnell, MD, University of Chicago
Edith Nutescu, PharmD, University of Illinois at Chicago
Kevin O’Leary, MD, Northwestern University
Please visit the Resources page for more information on prior research related to pharmacogenomic recommendations and race.