Comparison of hospitalization costs for the same adverse reaction associated with different medications.

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.

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System.

Importance: Using real-world data, the US Department of Veterans Affairs (VA) initiated a surveillance evaluation of edaravone after its approval for amyotrophic lateral sclerosis (ALS) in 2017. The use and safety of edaravone for patients with ALS in the VA health care system remain to be assessed. Objective: To describe a pharmacovigilance surveillance initiative with edaravone to monitor patient characteristics, utilization (edaravone cycles and riluzole use), and safety and to evaluate safety/effectiveness. Design, Setting, and Participants: This propensity score-matched cohort study used data on 369 patients with documented definite or probable ALS in the Veterans Health Administration (VHA) with at least 1 prescription for edaravone between August 1, 2017, and September 30, 2019. The analysis compared edaravone (alone or with riluzole) with riluzole only. For chronic users (≥6 months of drug), a time-to-event model evaluated ALS-related outcomes, with censoring at outcome, death, or end of evaluation. Patients with Parkinson disease, dementia, schizophrenia, or significant respiratory insufficiency per diagnosis codes within 2 years before prescription initiation were excluded. In overall matched cohorts, 223 patients treated with edaravone were 1:3 propensity score matched based on predefined confounders. For the chronic user subgroup analysis, 96 patients receiving edaravone and 424 patients receiving riluzole only were included. Exposures: Edaravone (alone or with riluzole) vs riluzole only. Main Outcomes and Measures: Patient characteristics, ALS drug use, and mortality. Acute outcomes (within 6 months of index) included proportion and mean time to event for death, discontinuation, or all-cause hospitalization, and outcomes for chronic users (receiving >6 months of treatment) included hazard ratios of outcomes related to disease-state progression. Results: Of 369 patients who received edaravone, most were older (mean [SD] age, 64.6 [11.3] years), male (346 [93.8%]), and White (261 [70.7%]). As of September 2019, 59.9% of edaravone patients had discontinued treatment; of those, 49.5% (108 of 218) received only 1 to 3 treatment cycles. Approximately 30% (110 patients) died. In a matched evaluation, significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole. Among chronic users, edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16). The death rate was lower with edaravone but the difference was not statistically significant. Conclusions and Relevance: Early edaravone discontinuation was common in the VA. Although outcomes favored use of riluzole only in the matched analysis, results should be interpreted with caution, as unmeasured bias in observational data is likely.

Impact of Dual Use of Department of Veterans Affairs and Medicare Part D Drug Benefits on Potentially Unsafe Opioid Use.

OBJECTIVES: To estimate the prevalence and consequences of receiving prescription opioids from both the Department of Veterans Affairs (VA) and Medicare Part D. METHODS: Among US veterans enrolled in both VA and Part D filling 1 or more opioid prescriptions in 2012 (n = 539 473), we calculated 3 opioid safety measures using morphine milligram equivalents (MME): (1) proportion receiving greater than 100 MME for 1 or more days, (2) mean days receiving greater than 100 MME, and (3) proportion receiving greater than 120 MME for 90 consecutive days. We compared these measures by opioid source. RESULTS: Overall, 135 643 (25.1%) veterans received opioids from VA only, 332 630 (61.7%) from Part D only, and 71 200 (13.2%) from both. The dual-use group was more likely than the VA-only group to receive greater than 100 MME for 1 or more days (34.3% vs 10.9%; adjusted risk ratio [ARR] = 3.0; 95% confidence interval [CI] = 2.9, 3.1), have more days with greater than 100 MME (42.5 vs 16.9 days; adjusted difference = 16.4 days; 95% CI = 15.7, 17.2), and to receive greater than 120 MME for 90 consecutive days (7.8% vs 3.1%; ARR = 2.2; 95% CI = 2.1, 2.3). CONCLUSIONS: Among veterans dually enrolled in VA and Medicare Part D, dual use of opioids was associated with more than 2 to 3 times the risk of high-dose opioid exposure.

Pharmacy Benefits Management in the Veterans Health Administration Revisited: A Decade of Advancements, 2004-2014.

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.

Cost-Effectiveness Analysis of Adjuvant Stage III Colon Cancer Treatment at Veterans Affairs Medical Centers.

The objective of this study was to evaluate the real-world cost effectiveness of adjuvant stage III colon cancer chemotherapy regimens, given that previous analyses have been based on data from clinical trials. The study was designed using integrated decision tree and Markov model, which was developed to evaluate the cost effectiveness of 5-fluorouracil/leucovorin (5-FU/LV), capecitabine, and the combination of each with oxaliplatin. The analysis was performed from a US Veterans Affairs perspective via retrospectively collected data, over a 5-year model time horizon. Outcome and cost data were used to calculate cost per quality adjusted life year (QALY), and one-way and probabilistic sensitivity analyses were performed. In the base case analysis, capecitabine and capecitabine plus oxaliplatin both cost more and were less effective than other regimens, and 5-FU/LV plus oxaliplatin, compared to 5-FU/LV alone, resulted in a cost of $25,997 per QALY gained. Model results were generally robust to parameter variation. Capecitabine plus oxaliplatin could be economically reasonable if full dosing occurred ≥76% of the time (base case 42%). In a real-world setting, the addition of oxaliplatin to 5-FU/LV is more effective but also more costly than 5-FU/LV alone. If full dosing of capecitabine-containing regimens can be assured, they may also be cost-effective strategies.

Incremental cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent clinics for non-dialysis-dependent chronic kidney disease patients.

BACKGROUND: Pharmacists successfully manage patients with anemia and chronic kidney disease (CKD), but the cost effectiveness of these programs is unknown. OBJECTIVE: To compare the cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent (ESA) clinics with that of usual care in patients with non-dialysis-dependent (NDD)-CKD. METHODS: A Markov model was used to estimate the incremental cost effectiveness of pharmacist-managed ESA clinics compared with usual care in outpatient veterans receiving ESAs for NDD-CKD in 2009. The analysis was conducted from a US Veterans Health Administration perspective with a 5-year time horizon, and the year of valuation for cost results was 2012. The effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. RESULTS: In the deterministic base case analysis, costs and effectiveness per patient over 5 years were US$13,412 and 2.096 quality-adjusted life-years (QALYs) in the pharmacist-managed ESA clinics and US$16,173 and 2.093 QALYs in usual care; ESA clinics dominated usual care. In one-way sensitivity analyses, ESA clinics no longer dominated if their patients' probability of being in the target hemoglobin range fell to 52 % (base case 71 %) or if the mean cost/patient/month of epoetin or darbepoetin in ESA clinics increased to approximately US$382 (base case US$226) or US$477 (base case US$268), respectively. When all parameters were varied simultaneously in a probabilistic sensitivity analysis, ESA clinics were favored ≥80 % of the time at willingness-to-pay thresholds of US$0-$100,000 per QALY gained. CONCLUSIONS: Pharmacist-managed ESA clinics were less costly and more effective than usual care in patients receiving ESAs for anemia and NDD-CKD. Results were robust to variation and support the use of pharmacist-managed ESA clinics.

Active surveillance of postmarket medical product safety in the Federal Partners' Collaboration.

After half a century of monitoring voluntary reports of medical product adverse events, the Food and Drug Administration (FDA) has launched a long-term project to build an adverse events monitoring system, the Sentinel System, which can access and evaluate electronic health care data to help monitor the safety of regulated medical products once they are marketed. On the basis of experience gathered through a number of collaborative efforts, the Federal Partners' Collaboration pilot project, involving FDA, the Centers for Medicare & Medicaid Services, the Department of Veteran Affairs, and the Department of Defense, is already enabling FDA to leverage the power of large public health care databases to assess, in near real time, the utility of analytical tools and methodologies that are being developed for use in the Sentinel System. Active medical product safety surveillance is enhanced by use of these large public health databases because specific populations of exposed patients can be identified and analyzed, and can be further stratified by key variables such as age, sex, race, socioeconomic status, and basis for eligibility to examine important subgroups.

Incremental cost-effectiveness of various monthly doses of vardenafil.

OBJECTIVE: To compare the cost-effectiveness of four, six, and eight doses per month of vardenafil in the context of pharmacy benefit decision making. METHODS: A Markov model was used to estimate the incremental cost-effectiveness of zero, four, six, or eight doses of vardenafil per month in hypothetical cohorts of 60-year-old male veterans with erectile dysfunction. Efficacy values for vardenafil were obtained from the literature, and vardenafil costs were obtained from Veterans Affairs pharmacy data. The analysis was conducted from a third-party payer perspective with a lifetime horizon, and the effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. RESULTS: In the base case analysis, the cost per quality-adjusted life-year gained for four doses of vardenafil per month compared with no therapy was $576. Six doses per month compared with four cost $2585/quality-adjusted life-year gained, and eight doses per month compared with six cost $5169/quality-adjusted life-year gained. In one-way sensitivity analyses of six doses per month compared with four, variation of two parameters caused the incremental cost-effectiveness ratio to cross a willingness-to-pay threshold of $20,000: when the increased utility associated with giving two additional doses/month was less than 0.001 (baseline 0.01) and when the cost per dose increased to $15.00 (baseline $1.69). CONCLUSION: Although four doses per month of vardenafil was the most cost-effective strategy, the use of six or eight doses per month also compares favorably with other accepted medical treatments. The results were stable across a range of inputs and help to support the current Veterans Affairs policy on the number of vardenafil doses provided per month for erectile dysfunction.

Increasing copayments and adherence to diabetes, hypertension, and hyperlipidemic medications.

OBJECTIVE: To examine the impact of a medication copayment increase on adherence to diabetes, hypertension, and hyperlipidemic medications. STUDY DESIGN: Retrospective pre-post observational study. METHODS: This study compared medication adherence at 4 Veterans Affairs medical centers between veterans who were exempt from copayments and propensity-matched veterans who were not exempt. The diabetes sample included 1069 exempt veterans and 1069 nonexempt veterans, the hypertension sample included 3545 exempt veterans and 3545 nonexempt veterans, and the sample of veterans taking statins included 2029 exempt veterans and 2029 nonexempt veterans. The main outcome measure was medication adherence 12 months before and 23 months after the copayment increase. Adherence differences were assessed in a difference-in-difference approach by using generalized estimating equations that controlled for time, copayment exemption, an interaction between time and copayment exemption, and patient demographics, site, and other factors. RESULTS: Adherence to all medications increased in the short term for all veterans, but then declined in the longer term (February-December 2003). The change in adherence between the preperiod and the postperiod was significantly different for exempt and nonexempt veterans in all 3 cohorts, and nonadherence increased over time for veterans required to pay copayments. The impact of the copayment increase was particularly adverse for veterans with diabetes who were required to pay copayments. CONCLUSION: A $5 copayment increase (from $2 to $7) adversely impacted medication adherence for veterans subject to copayments taking oral hypoglycemic agents, antihypertensive medications, or statins.

Drug costs and use in VHA nursing homes: a national overview of long-stay residents.

OBJECTIVES: The aim of this study was to provide national annualized estimates of drug costs and use by drug classes for long-stay nursing home (NH) residents. DESIGN: National, descriptive, secondary data analysis. SETTING: National, Veterans Health Administration (VHA), 136 NHs. PARTICIPANTS: Our study population consisted of 6554 VHA long-stay NH residents, identified from the Minimum Data Set (MDS), who had an annual assessment during FY 2005 linked with 8,847,561 inpatient pharmacy claims. MEASUREMENT: Descriptive statistics of the annual drug costs and use by VHA therapeutic drug classes obtained from FY 2005 national pharmacy claims linked at the individual resident level. RESULTS: The total cost of the drugs was $23,782,717 in 326 drug classes for 6554 VHA NH residents. Average annual drug cost was $3629 per resident (99% Confidence Interval [CI], $3343-$3915). The top 20 drug classes accounted for nearly 70% of total drug costs for long-stay NH residents. Approximately three quarters (73.3%) of these residents received a non-opioid analgesic (eg, acetaminophen, aspirin). Over half of these residents received antidepressants (selective serotonin reuptake inhibitors [SSRIs]) (54.3%), or other anti-infective drugs (eg, bacitracin, ciprofloxacin) (53.3%). CONCLUSIONS: This is the first national study of drug costs and use for long-stay veterans in VHA NHs. It is essential in any study analyzing drug costs and use in NH patients to differentiate long-stay residents from short-stay patients. This kind of detailed cost and use analysis has implications for projecting future costs associated with the Medicare Part D prescription benefit for dually eligible NH residents.

Pharmacy benefits management in the Veterans Health Administration: 1995 to 2003.

The Department of Veterans Affairs (VA) Pharmacy Benefits Management Strategic Healthcare Group (VA PBM) oversees the formulary for the entire VA system, which serves more than 4 million veterans and provides more than 108 million prescriptions per year. Since its establishment in 1995, the VA PBM has managed pharmaceuticals and pharmaceutical-related policies, including drug safety and efficacy evaluations, pharmacologic management algorithms, and criteria for drug use. These evidence-based practices promote, optimize, and assist VA providers with the safe and appropriate use of pharmaceuticals while allowing for formulary decisions that can result in substantial cost savings. The VA PBM also has utilized various contracting techniques to standardize generic agents as well as specific drugs and drug classes (eg, antihistamines, angiotensin-converting enzyme inhibitors, alpha-blockers, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [statins]). These methods have enabled the VA to save approximately dollar 1.5 billion since 1996 even as drug expenditures continued to rise from roughly dollar 1 billion in fiscal year (FY) 1996 to more than dollar 3 billion in FY 2003. Furthermore, the VA PBM has established an outcomes research section to undertake quality-improvement and safety initiatives that ultimately monitor and determine the clinical impact of formulary decisions on the VA system nationwide. The experiences of this pharmacy benefits program, including clinical and contracting processes/procedures and their impact on the VA healthcare system, are described.