Evaluating Pharmacogenomic Prescription Data in the Military Health System

INTRODUCTION: Pharmacogenomic testing (PGx) is often completed after an adverse drug event (ADE) has occurred, but moving toward a preemptive rather than reactive testing approach could potentially decrease preventable drug-related hospitalizations and positively impact combat readiness. Although prior research has suggested that PGx testing may aid in individual patient medical management, there is limited research assessing the potential impact of preemptive PGx testing in the Military Health System (MHS). In this study, we utilized MHS prescription data along with available genotypic and phenotypic population frequency data to estimate the potential impact of PGx testing in the diverse MHS patient population.

MATERIALS AND METHODS: A retrospective cross-sectional study was conducted using fiscal year 2021 (FY21) prescription data from the Defense Health Agency (DHA) Pharmacy Operations Division. Medications that had Clinical Pharmacogenetics Implementation Consortium (CPIC) level A, A/B, and B designations prescribed to Active Duty, Reserve, Retired, and Dependent MHS beneficiaries ages 18 and up were included in the analyses. We evaluated the prescription count along with the age, biological sex, and MHS beneficiary status for medications prescribed within the MHS. We then estimated the number of MHS beneficiaries predicted to have non-normal metabolism of a given PGx-related medication. This data was presented as a range based on the CPIC allele and metabolizer frequency data which varies across PharmGKB-defined biogeographical groups. This study was approved and was determined exempt by the Uniformed Services University of Health Sciences (USUHS) and the Augustana University institutional review boards.

RESULTS: There were over 8 million unique prescriptions for 83 PGx-related medications with CPIC level A, A/B, or B designation in FY21. Of these, over 1.2 million prescriptions (15%) were for Active Duty and Reserve members, with the top 5 prescribed PGx-related medications for Active Duty members being ibuprofen, ondansetron, hydrocodone, omeprazole, and meloxicam. This study further analyzed 64 medications with known metabolism frequency data. In FY21, there were up to 632,974 MHS beneficiaries taking omeprazole who were predicted to have non-normal CYP2C19 metabolism, which represents the medication with the highest number of prescriptions among individuals with estimated non-normal metabolism. Among medications with a risk for severe ADE, allopurinol was at the top with up to 301 prescriptions provided to Active Duty members estimated to have the *58:01 variant, which is associated with increased risk for toxic epidermal necrolysis.

CONCLUSIONS: Currently, PGx testing is an underutilized resource in the MHS system, despite the many PGx-related medications that are widely prescribed among all MHS beneficiaries who have actionable CPIC guidelines. Based on published allele and metabolizer frequencies in the general population, a significant number of MHS beneficiaries taking these medications may be predicted to have non-normal metabolism and be at increased risk for adverse drug events and/or therapeutic failure. Given high prescription counts across all MHS beneficiaries, including Active Duty members, this data should be used to inform a preemptive PGx testing implementation approach in the MHS with the goal to reduce ADEs and therapeutic failure, while improving readiness among service members.