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Pharmacogenetic (PGx) testing before initiation of thiopurine treatment and CBC monitoring post-initiation helps avoid adverse events and ensure patient safety. This study aims to evaluate trends in PGx testing and CBC monitoring among Veterans prescribed azathioprine, thioguanine, or mercaptopurine to demonstrate VA's efforts to improve medication safety after an adverse event. To assess testing patterns, we used VA electronic health report data to identify 20,524 Veterans who first began thiopurine treatment between January 1, 2010, to December 31, 2021. Aggregate monthly counts of thiopurine prescriptions and associated lab tests were tabulated, and the trend in the proportion of patients tested was analyzed using the Mann-Kendall test. The proportion of patients undergoing PGx testing rose from 30.0% in 2010 to 47.5% in late 2014 (July-December). However, PGx testing and overall testing only increased slightly after the sentinel event, and orders levelled off over time at slightly lower levels than before the sentinel event. Very little change was seen in the overall proportion of individuals receiving any testing across all patients with new prescriptions from the time of the sentinel event in 2014 to the end of 2021. A large portion of patients prescribed thiopurine drugs did not receive testing that could help prevent the development of potential adverse events, leading to a predominantly reactive approach. Increased PGx testing may result in a more proactive approach to the prevention of adverse events due to genetic interaction.
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PURPOSE: To describe the implementation of clinical decision support tools for alerting prescribers of actionable drug-gene interactions in the Veterans Health Administration (VHA). SUMMARY: Drug-gene interactions have been the focus of clinicians for years. Interactions between SCLO1B1 genotype and statin medications are of particular interest as these can inform risk for statin-associated muscle symptoms (SAMS). VHA identified approximately 500,000 new users of statin medications prescribed in VHA in fiscal year 2021, some of whom could benefit from pharmacogenomic testing for the SCLO1B1 gene. In 2019, VHA implemented the Pharmacogenomic Testing for Veterans (PHASER) program to offer panel-based, preemptive pharmacogenomic testing and interpretation. The PHASER panel includes SLCO1B1, and VHA utilized Clinical Pharmacogenomics Implementation Consortium statin guidelines to build its clinical decision support tools. The program's overarching goal is to reduce the risk of adverse drug reactions such as SAMS and improve medication efficacy by alerting practitioners of actionable drug-gene interactions. We describe the development and implementation of decision support for the SLCO1B1 gene as an example of the approach being used for the nearly 40 drug-gene interactions screened for by the panel. CONCLUSION: The VHA PHASER program identifies and addresses drug-gene interactions as an application of precision medicine to reduce veterans' risks for adverse events. The PHASER program's implementation of statin pharmacogenomics utilizes a patient's SCLO1B1 phenotype to alert providers of the risk for SAMS with the statin being prescribed and how to lower that risk through a lower dose or alternative statin selection. The PHASER program may help reduce the number of veterans who experience SAMS and may improve their adherence to statin medications.
Subject(s)
Decision Support Systems, Clinical , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pharmacogenetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Veterans Health , Precision MedicineABSTRACT
PURPOSE: Costs of hospitalization due to severe adverse drug reactions (ADRs) were previously estimated within the Veterans Health Administration (VHA), but additional analyses are needed to infer potential interventions to mitigate these negative outcomes. The objective of this study was to compare specific adverse reaction-related hospitalization costs between medications with similar indications. METHODS: Mean hospitalization costs associated with the same ADR symptom were compared for different drugs with similar indications using adjusted generalized linear models with a Bonferroni correction for multiple comparisons as well as a gamma distribution. RESULTS: Overall, hospitalization costs between medications with similar indications were not significantly different for specific adverse reactions. However, gastrointestinal hemorrhage-associated costs were higher for warfarin versus nonsteroidal anti-inflammatory drugs (model estimate of mean cost, $18,114 [range of lower and upper model estimates, $12,522-$26,202] vs $14,255 [estimate range, $9,710-$20,929]). Similarly, the estimated mean hospitalization cost associated with angioedema was higher for losartan versus lisinopril or lisinopril/hydrochlorothiazide: $14,591 (range, $9467-$22,488) versus $8,935 (range, $6,301-$12,669) and $8,022 (range, $5,424-$11,865), respectively. CONCLUSION: Although we found few differences in the cost of hospitalization when comparing drugs with similar indications and the same adverse reaction, there were specific drug-ADR pairs that merit attention and consideration of interventions to improve safe and appropriate medication use. Evaluation of the effect of those interventions on the incidence of ADRs is an area for future study.
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Drug-Related Side Effects and Adverse Reactions , Lisinopril , Humans , Pharmaceutical Preparations , Hospitalization , Drug-Related Side Effects and Adverse Reactions/epidemiology , IncidenceSubject(s)
Costs and Cost Analysis , Drug-Related Side Effects and Adverse Reactions/economics , Hospitalization/economics , Hospitalization/statistics & numerical data , Veterans Health/economics , Veterans Health/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , United StatesABSTRACT
Dimethyl fumarate (DMF), a treatment for multiple sclerosis, may cause leukopenia and infection. Accordingly, periodic white blood cell (WBC) monitoring is recommended. We sought to evaluate the US Department of Veteran Affairs' safety program which provides facilities with a list of patients prescribed DMF therapy without a documented white blood cell count (WBC). We identified 118 sites with patients treated with DMF from 1 January 2016 through 30 September 2016. Each site was asked if any of seven interventions were used to improve WBC monitoring (academic detailing, provider education without academic detailing, electronic clinical reminders, request for provider action plan, draft orders for WBC monitoring, patient mailings, and patient calls). The survey response rate was 78%. For the 92 responding sites (78%) included sites (1115 patients) the mean rate of WBC monitoring was 54%. In multivariate analysis, academic detailing increased the rate by 17% (95% CI 4 to 30%, p = 0.011) and provider education increased the rate by 9% (95% CI 0.6 to 18%, p = 0.037). The WBC monitoring rate increased by 3.8% for each additional intervention used (95% CI 1.2-6.4%, p = 0.005). Interventions focused on the physician, including academic detailing, were associated with improved WBC monitoring for patients at risk for leukopenia from DMF treatment.
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Multiple Sclerosis , Physicians , Veterans , Dimethyl Fumarate/therapeutic use , Humans , Leukocytes , Multiple Sclerosis/drug therapyABSTRACT
PURPOSE: To examine the reporting rates of adverse drug events (ADEs) with apixaban and empagliflozin as reports move up to the next level of spontaneous reporting. METHODS: This was a retrospective cohort study of outpatients who discontinued apixaban or empagliflozin within 3 years of Food and Drug Administration (FDA) approval. We enriched the sample using an active surveillance strategy to identify subsets of patients with International Classification of Diseases (ICD) codes possibly associated with an ADE. Stratified random samples of charts were reviewed to determine if patients discontinued the medication due to an ADE. If so, we ascertained whether these were uploaded into the Veterans Administration (VA) electronic health record reporting system (Adverse Reaction Tracking System [ARTS]), VA national Web-based system (VA Adverse Drug Event Reporting System [VA ADERS]), and FDA MedWatch. RESULTS: From the cohort of 2,973 patients who discontinued apixaban, 321 patients (10.8%) were randomly sampled for chart review (including 61 patients with relevant ICD codes). During chart review, 88 ADEs were identified, with 40/61 (65.6%) from the subset with ICD codes. Of the total of 88 ADEs, 18.2%, 10.2%, and 6.8% were reported in ARTS, VA ADERS, and MedWatch, respectively. Of the 1,555 patients who discontinued empagliflozin, 179 patients (11.5%) were randomly sampled for chart review (40 patients with relevant ICD codes). During chart review, 78 ADEs were identified, with 19/40 (47.5%) from the subset with ICD codes. Of the 78 ADEs, 28.2%, 19.2%, and 7.7% were reported in ARTS, VA ADERS, and MedWatch, respectively. CONCLUSION: We found substantial underreporting of apixaban and empagliflozin ADEs that became worse at each higher level of spontaneous reporting.
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Adverse Drug Reaction Reporting Systems/statistics & numerical data , Benzhydryl Compounds/adverse effects , Glucosides/adverse effects , Pyrazoles/adverse effects , Pyridones/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , United States Department of Veterans Affairs/statistics & numerical data , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , Sociobiology , United StatesABSTRACT
PURPOSE: Adverse drug events (ADEs) in the U.S. Department of Veterans Affairs (VA) were evaluated, and differences in age group report rates and reported medications in different age groups were assessed. METHODS: We utilized the VA Adverse Drug Event Reporting System (ADERS) to assess 10-year age groups regarding ADE reporting rates, event severity, and associated reported medications. Data were derived from 484,351 ADE reports from 395,703 patients included in VA ADERS from 2009 through 2016. RESULTS: Reported rates of ADEs per 10,000 unique users demonstrated a nonlinear relationship with age, peaking in the group aged 60-69 years (148.6 reports/10,000 unique users) and declining thereafter. However, the percentage of adverse events reported as severe consistently rose with age group (3% in patients age 20-29 years versus 6% in patients older than 90 years). The types of medications reported as causative agents shifted over time from predominantly mental health and pain medications in younger veterans (e.g., age 20-29 years) to medications for chronic diseases in older cohorts (e.g., age 60-69 years). CONCLUSION: An analysis of VA ADE reports revealed a nonlinear relationship between age and events, with events peaking at age 60-69 years. Rates of severe ADEs increased in older age groups. Drugs commonly associated with ADEs tended to be those primarily used for mental health and pain treatment in younger patients and those used to address chronic disease states in older patients.
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Adverse Drug Reaction Reporting Systems/standards , Drug-Related Side Effects and Adverse Reactions/epidemiology , Hospitals, Veterans/standards , Severity of Illness Index , United States Department of Veterans Affairs/standards , Adult , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Drug-Related Side Effects and Adverse Reactions/diagnosis , Female , Hospitals, Veterans/statistics & numerical data , Humans , Male , Middle Aged , Polypharmacy , Retrospective Studies , United States/epidemiology , United States Department of Veterans Affairs/statistics & numerical data , Veterans/statistics & numerical data , Young AdultABSTRACT
PURPOSE: Results of a study to estimate the prevalence of look-alike/sound-alike (LASA) medication errors through analysis of Veterans Affairs (VA) administrative data are reported. METHODS: Veterans with at least 2 filled prescriptions for 1 medication in 20 LASA drug pairs during the period April 2014-March 2015 and no history of use of both medications in the preceding 6 months were identified. First occurrences of potential LASA errors were identified by analyzing dispensing patterns and documented diagnoses. For 7 LASA drug pairs, potential errors were evaluated via chart review to determine if an actual error occurred. RESULTS: Among LASA drug pairs with overlapping indications, the pairs associated with the highest potential-error rates, by percentage of treated patients, were tamsulosin and terazosin (3.05%), glipizide and glyburide (2.91%), extended- and sustained-release formulations of bupropion (1.53%), and metoprolol tartrate and metoprolol succinate (1.48%). Among pairs with distinct indications, the pairs associated with the highest potential-error rates were tramadol and trazodone (2.20%) and bupropion and buspirone (1.31%). For LASA drug pairs found to be associated with actual errors, the estimated error rates were as follows: lamivudine and lamotrigine, 0.003% (95% confidence interval [CI], 0-0.01%); carbamazepine and oxcarbazepine, 0.03% (95% CI, 0-0.09%); and morphine and hydromorphone, 0.02% (95% CI, 0-0.05%). CONCLUSION: Through the use of administrative databases, potential LASA errors that could be reviewed for an actual error via chart review were identified. While a high rate of potential LASA errors was detected, the number of actual errors identified was low.
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Databases, Factual , Medication Errors/prevention & control , United States Department of Veterans Affairs , Adolescent , Adult , Aged , Aged, 80 and over , Drug Labeling , Drug Prescriptions/standards , Female , Hospitals, Veterans , Humans , Male , Medication Systems, Hospital/organization & administration , Middle Aged , Outpatients , United States , Young AdultABSTRACT
Over the past decade, the Department of Veterans Affairs (VA) Pharmacy Benefits Management Services (PBM) has enhanced its formulary management activities and added programs to ensure that the national drug plan continues to meet the pharmacy needs of veterans and to promote safe and appropriate drug therapy in the face of rising medication expenditures. This article describes the broad range of services provided by the VA PBM that work in partnership to deliver a high-quality and sustainable pharmacy benefit for veterans. In support of formulary management, VA PBM pharmacists prepare extensive clinical guidance documents (e.g., drug monographs and criteria for use) that are used by physicians and pharmacists with operational and clinical oversight of the VA national formulary. The VA PBM has utilized various contracting techniques and continually evaluates drug utilization data to identify opportunities for potential savings. Remarkably, since before 2004, the average acquisition cost for a 1-month supply of medication has remained fairly stable at approximately $13-$15. Two new VA PBM programs are the VA Center for Medication Safety (VA MedSAFE) and the Clinical Pharmacy Practice Office (CPPO). VA MedSAFE is a comprehensive pharmacovigilance program focused on the detection, assessment, and prevention of adverse drug events, and CPPO is dedicated to improving safe and appropriate medication use by supporting and expanding clinical pharmacy practice. Moving forward, the VA PBM will consider new initiatives to stay at the forefront of providing quality care while maintaining economic viability. DISCLOSURES: No outside funding supported this research. This work was supported by VA Pharmacy Benefits Management Services (VA PBM), Hines, Illinois, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Glassman is co-director of the VA Center for Medication Safety, which is part of the VA PBM. He is also part of the Medical Advisory Panel for the VA PMB. All other authors are employed by the VA PBM. The views expressed in this article are those of the authors, and no official endorsement by the U.S. Department of Veteran Affairs or the U.S. government is intended or should be inferred. Study concept and design were contributed by Valentino, Cunningham, Good, Aspinall, and Sales. Calabrese and Ourth took the lead in data collection, along with Good, Cunningham, Aspinall, Sales, Burk, Moore, Neuhauser, and Golterman. Data interpretation was performed by Burk, Newhauser, and Golterman, along with Glassman, Calabrese, Moore, and Ourth. The manuscript was written by Aspinall and Sales, along with Burk, Newhauser, Golterman, Ourth, and Cunningham. Good, Glassman, and Moore revised the manuscript, along with Calabrese, Valentino, and Aspinall.
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Insurance Benefits/trends , Pharmacists/trends , Pharmacopoeias as Topic , Pharmacy Service, Hospital/trends , United States Department of Veterans Affairs/trends , Veterans Health/trends , Humans , Insurance Benefits/methods , Pharmacists/organization & administration , Pharmacy Service, Hospital/organization & administration , Time Factors , United States/epidemiology , United States Department of Veterans Affairs/organization & administrationABSTRACT
PURPOSE: A Web-based application for coordinating medication-use evaluation (MUE) initiatives within the Veterans Affairs (VA) health care system is described. SUMMARY: The MUE Tracker (MUET) software program was created to improve VA's ability to conduct national medication-related interventions throughout its network of 147 medical centers. MUET initiatives are centrally coordinated by the VA Center for Medication Safety (VAMedSAFE), which monitors the agency's integrated databases for indications of suboptimal prescribing or drug therapy monitoring and adverse treatment outcomes. When a pharmacovigilance signal is detected, VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads patient lists to the secure MUET application, where locally designated personnel (typically pharmacists) can access and use the data to target risk-reduction efforts. Local data on patient-specific interventions are stored in a centralized database and regularly updated to enable tracking and reporting for surveillance and quality-improvement purposes; aggregated data can be further analyzed for provider education and benchmarking. In a three-year pilot project, the MUET program was found effective in promoting improved prescribing of erythropoiesis-stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated patients in all specified trigger groups. The MUET initiative has since been expanded to target other high-risk drugs, and efforts are underway to refine the tool for broader utility. CONCLUSION: The MUET application has enabled the increased standardization of medication safety initiatives across the VA system and may serve as a useful model for the development of pharmacovigilance tools by other large integrated health care systems.
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Drug Utilization Review/methods , Hospitals, Veterans/organization & administration , Internet , Practice Patterns, Physicians'/standards , Benchmarking , Databases, Factual , Drug Monitoring/methods , Drug-Related Side Effects and Adverse Reactions/epidemiology , Hematinics/therapeutic use , Hospitals, Veterans/standards , Humans , Pharmacovigilance , Pilot Projects , Program Development , Quality Improvement , Software , United States , VeteransABSTRACT
PURPOSE: The improvement and linkage of two Department of Veterans Affairs (VA) databases for monitoring adverse drug reactions (ADRs) are described, with a discussion of the potential implications for improved medication safety within the VA health care system. SUMMARY: Before 2007, VA had limited capability to track and evaluate ADRs across its nationwide network of health care facilities. Since then, VA has established a standardized monitoring system that has improved the reporting, analysis, and trending of ADRs reported by providers and pharmacists at individual VA facilities. The enhanced system has two components with distinct but complementary functions: the Adverse Reaction Tracking database, which is derived by extracting text-based, patient-specific information entered into the VA electronic medical record system by clinicians at the point of care; and the VA Adverse Drug Event Reporting System (VA ADERS), an external web-based portal that contains aggregated data from 146 VA facilities, with standardized coding of reported events. Both databases allow for ADR reporting at the local, regional, and national levels. The VA ADERS database permits rapid electronic reporting of certain ADRs to the federal MedWatch program. The two databases can be used in tandem for more comprehensive assessments of ADR patterns and reporting rates and to generate a wide range of benchmarking data. CONCLUSION: In recent years, the refinement of two databases for ADR reporting has increased VA's capability to systematically monitor, track, and report ADRs across its national network of health care facilities. Linking the two databases has further strengthened those capabilities, enhancing medication safety practices and aiding in pharmacovigilance.