Evaluation of medical costs avoided when new oral anticoagulants are used for extended treatment of venous thromboembolism based on clinical trial results.

This study evaluated avoidances in medical costs associated with clinical endpoints from randomized clinical trials that evaluated the efficacy and safety of the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban for extended treatment of patients with venous thromboembolism (VTE). Event rates of efficacy and safety endpoints from the clinical trials (RE-SONATE, EINSTEIN-EXT, and AMPLIFY-EXT) were obtained from published literature. Incremental annual medical costs among patients with clinical events from a US payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical endpoints for patients treated with NOACs versus placebo were then estimated. One-way univariate and Monte Carlo sensitivity analyses were additionally carried out. In all three NOAC trials lower rates of recurrent VTE occurred with NOAC use versus placebo. As a result of the reduction in VTE recurrence the overall medical costs avoided were -$2,794, -$2,948, -$4,249, and -$4,244 for VTE patients treated with dabigatran, rivaroxaban, apixaban 2.5 mg, and apixaban 5 mg respectively versus patients treated with placebo. Apixaban was associated with the greatest avoidance in medical costs, which was driven mainly by a greater reduced rate in recurrent VTE than other NOACs versus placebo and also a reduction in major bleeding rate. Further evaluation is needed to validate these results in the real-world setting.

Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

Janus Kinase Inhibitor Therapy and Risk of Age-Related Macular Degeneration in Autoimmune Disease.

Importance: The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management. Objective: To determine whether Janus kinase inhibitors (JAKis) are associated with a reduced risk of AMD development in patients with autoimmune diseases. Design, Setting, and Participants: This retrospective observational cohort study used administrative claims data from Merative MarketScan research databases (Commercial and Medicare Supplemental) and Optum Clinformatics Data Mart databases between January 1, 2010, and January 31, 2022. Patients with autoimmune diseases satisfying study eligibility criteria and who received JAKi treatment (9126 in MarketScan and 5667 in Optum) were propensity score matched (1:1) to identical numbers of study-eligible patients who received non-JAKi-based immunotherapy. Exposure: Treatment duration of 6 months or longer. Main Outcomes and Measures: Incidence rates of AMD (exudative and nonexudative) over the first 6 to 18 months of treatment were determined, and bayesian Poisson regression models were used to estimate incidence rate ratios, 95% CIs, and posterior probabilities of AMD. Results: After matching, female sex represented the majority of the patient population in both MarketScan and Optum (14 019/18 252 [76.6%] and 8563/3364 [75.2%], respectively in the JAKi patient population). More than 60% of the patient population was older than 55 years of age in both cohorts. Over the specified treatment period, a 49% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (10/9126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% CI, 0.19-0.90) vs those who received non-JAKi therapy (43/9126 events; AIRR, 1 [reference]) in MarketScan, and a 73% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (3/5667 events; AIRR, 0.27; 95% CI, 0.03-0.74) vs those who received non-JAKi therapy (21/5667 events; AIRR, 1 [reference]) in Optum. The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. Posterior probabilities of the adjusted risk being less than unity were 97.6% (MarketScan) and 98.9% (Optum) for those who received JAKi therapy vs those who received non-JAKi therapy in MarketScan and Optum, respectively. Conclusions and Relevance: JAKi use may be associated with a reduced risk of incident AMD in US adults with major autoimmune diseases. The absolute percentage reduction is consistent with a potential role for JAKi in this population. Future studies with long-term follow-up are recommended to investigate the association between JAKi use and incident AMD in other disease indications. Investigation into the role of systemic inflammation and JAK-signal transducers and activators of transcription signaling in AMD may improve understanding of the pathophysiology of AMD and lead to new treatment options.

Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians.

BACKGROUND: Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months. METHODS: Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients' depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score <5 at 6 months; response was defined as a score reduction ≥50%. RESULTS: Among patients with baseline PHQ-9 score ≥5, 45.0% achieved remission (46.7% intervention versus 42.8% control) and 63.9% responded (67.0% intervention versus 59.7% control) at 6 months. After adjusting for baseline demographic and clinical variables, odds of remission (odds ratio [OR], 1.59 [95% CI, 1.07-2.37]) or response (OR, 2.02 [95% CI, 1.36-3.02]) were significantly greater for the intervention group than for control patients. CONCLUSIONS: This study demonstrated that regular patient symptom monitoring with feedback to physicians improved outcomes of depression treatment in the primary care setting. Determining reasons for the high observed nonremission rates requires further investigation.

Cost-effectiveness of adjunctive therapy with atypical antipsychotics for acute treatment of major depressive disorder.

BACKGROUND: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. OBJECTIVE: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. METHODS: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. RESULTS: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. CONCLUSIONS: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

One-year risk of psychiatric hospitalization and associated treatment costs in bipolar disorder treated with atypical antipsychotics: a retrospective claims database analysis.

BACKGROUND: This study compared 1-year risk of psychiatric hospitalization and treatment costs in commercially insured patients with bipolar disorder, treated with aripiprazole, ziprasidone, olanzapine, quetiapine or risperidone. METHODS: This was a retrospective propensity score-matched cohort study using the Ingenix Lab/Rx integrated insurance claims dataset. Patients with bipolar disorder and 180 days of pre-index enrollment without antipsychotic exposure who received atypical antipsychotic agents were followed for up to 12 months following the initial antipsychotic prescription. The primary analysis used Cox proportional hazards regression to evaluate time-dependent risk of hospitalization, adjusting for age, sex and pre-index hospitalization. Generalized gamma regression compared post-index costs between treatment groups. RESULTS: Compared to aripiprazole, ziprasidone, olanzapine and quetiapine had higher risks for hospitalization (hazard ratio 1.96, 1.55 and 1.56, respectively; p < 0.05); risperidone had a numerically higher but not statistically different risk (hazard ratio 1.37; p = 0.10). Mental health treatment costs were significantly lower for aripiprazole compared with ziprasidone (p = 0.004) and quetiapine (p = 0.007), but not compared to olanzapine (p = 0.29) or risperidone (p = 0.80). Total healthcare costs were significantly lower for aripiprazole compared to quetiapine (p = 0.040) but not other comparators. CONCLUSIONS: In commercially insured adults with bipolar disorder followed for 1 year after initiation of atypical antipsychotics, treatment with aripiprazole was associated with a lower risk of psychiatric hospitalization than ziprasidone, quetiapine, olanzapine and risperidone, although this did not reach significance with the latter. Aripiprazole was also associated with significantly lower total healthcare costs than quetiapine, but not the other comparators.

Evaluation of Adherence and Persistence Differences Between Adalimumab Citrate-Free and Citrate Formulations for Patients with Immune-Mediated Diseases in the United States.

INTRODUCTION: Our aim was to evaluate patient adherence and persistence with citrate-free adalimumab (ADA-CF), introduced in 2018 to reduce injection-site pain, compared with citrate-containing adalimumab (ADA-C). METHODS: This was a retrospective cohort study using a US claims database (IBM® MarketScan® Commercial and Medicare Supplemental Claims Database) from February 2018 to January 2020. Patients at least 18 years of age who were naïve to adalimumab 6 months before the index date (date of first adalimumab claim) and with at least 12 months of continuous medical and pharmacy coverage were eligible for the study. Adherence was assessed by determining the proportion of days covered (PDC) and the percentage of patients with PDC ≥ 80% during the 12-month follow-up period. Persistence was evaluated by measuring the rate of discontinuation and days to discontinuation (i.e., time on treatment) from the index date over the 12-month follow-up period. Continuous adherence outcomes (PDC) were evaluated using linear regression models. Binary adherence outcomes (PDC ≥ 80%) were assessed using logistic regression models. Kaplan-Meier analysis and Cox proportional hazards models were used to assess persistence outcomes. RESULTS: There were 2195 and 1005 patients in the ADA-CF and ADA-C cohorts, respectively, with most using adalimumab for rheumatoid arthritis (ADA-CF 29.7%, ADA-C 27.2%) and psoriasis (ADA-CF 24.5%, ADA-C 31.9%). Significantly greater adherence was achieved with ADA-CF compared with ADA-C (mean PDC [standard deviation] 0.68 [0.30] vs 0.61 [0.32], P < 0.0001). A significantly greater percentage of patients receiving ADA-CF (47.2%) vs ADA-C (39.6%) had PDC ≥ 80% (P < 0.0001). The discontinuation rate was significantly lower for the ADA-CF cohort (46.4%) compared with ADA-C (55.9%, P < 0.0001), resulting in a 27% lower likelihood of discontinuation during the 12-month follow-up period (hazard ratio 0.73; 95% confidence interval 0.66, 0.82; P < 0.0001) and longer time on treatment (260 vs 232 days, P < 0.0001). CONCLUSION: Adherence and persistence are significantly improved with ADA-CF compared with ADA-C.

Cost-sharing effects on adherence and persistence for second-generation antipsychotics in commercially insured patients.

PURPOSE: To assess the relationship between patient cost-sharing (e.g., copayments or coinsurance) and adherence and persistence to second-generation (atypical) antipsychotic (SGA) medications. DESIGN AND METHODOLOGY: A retrospective, observational study of adults aged 18-64 years with schizophrenia or bipolar disorder (n = 7,910) who initiated SGA medications with employer-sponsored insurance in the 2003-2006 MarketScan Commercial Claims and Encounters Database. Adherence was defined as percent of days covered in each calendar quarter. Persistence was defined as days from initiation of SGA to the first 90-day gap in medication on-hand. Generalized Estimating Equations were used to determine the effects of cost-sharing on adherence to SGA medications based on patient-quarter data. A Cox proportional hazards model with patient cost-sharing as a time-varying covariate estimated the effects on persistence with SGA medication. PRINCIPAL FINDINGS: Higher cost-sharing was associated with a lower likelihood of adherence. When compared to plans with cost-sharing below $10, adherence rates were approximately 27% lower for patients in plans with SGA cost-sharing of $50 and above and about 10% lower for patients in plans with cost-sharing between $30 and $50. In both cases, the reduction in adherence was significant. Higher cost-sharing was also associated with a shorter time to discontinuation (HR: 1.028; 95% CI [1.006-1.051]). CONCLUSION: High SGA cost-sharing appears to be a financial barrier to SGA medication compliance, especially when cost-sharing levels exceeded $30. Our findings have implications for health plans, employers, and policymakers who have, or are, contemplating establishing cost-sharing tiers for SCA medications for commercially insured patients with serious mental illnesses.

Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia: an international network study.

Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. Methods We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. Results 34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) individuals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website (http://evidence.ohdsi.org/Covid19CharacterizationHospitalization/). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 individuals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. Conclusions We provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of individuals hospitalised with COVID-19.

Time to psychiatric hospitalization in patients with bipolar disorder treated with a mood stabilizer and adjunctive atypical antipsychotics: a retrospective claims database analysis.

OBJECTIVE: This study compared the time to psychiatric hospitalization in commercially insured patients with bipolar disorder who were treated with a mood stabilizer plus adjunctive aripiprazole versus adjunctive ziprasidone, olanzapine, quetiapine, or risperidone. METHODS: This was a retrospective, propensity score-matched cohort study using the Ingenix I3/LabRx integrated insurance claims data set. Patients with bipolar disorder were included if they had >or=180 days of pre-index enrollment in the health plan without atypical antipsychotic exposure. Patients received mood stabilizers and subsequently received adjunctive atypical antipsychotic agents; they were then monitored for up to 90 days after the index antipsychotic prescription. The primary analysis was a Cox proportional hazards analysis to evaluate the time until psychiatric hospitalization comparing adjunctive aripiprazole with ziprasidone, olanzapine, quetiapine, or risperidone after adjusting for age, sex, and preindex hospitalization. RESULTS: Adjunctive aripiprazole was associated with a longer time until hospitalization than adjunctive ziprasidone, olanzapine, quetiapine, or risperidone (hazard ratios 1.7, 1.6, 1.5, and 1.5, respectively; all, P < 0.05). Mean initial and maximum doses of all drugs were below those recommended by the package insert or clinical practice guidelines. Sensitivity analyses suggested the robustness of the results in the general population of patients with bipolar disorder recently treated with atypical antipsychotics. CONCLUSIONS: This retrospective claims-data analysis suggests that in these adults with bipolar disorder treated with mood stabilizers, the addition of adjunctive aripiprazole was associated with a longer time to hospitalization than adjunctive ziprasidone, olanzapine, quetiapine, or risperidone during a 90-day follow-up period.

Healthcare costs associated with treatment of bipolar disorder using a mood stabilizer plus adjunctive aripiprazole, quetiapine, risperidone, olanzapine or ziprasidone.

OBJECTIVE: Bipolar disorder has an associated economic burden due to its treatment, including medication and hospitalization costs as well as costs associated with treatment of comorbid conditions. This study compared healthcare costs in patients treated with a mood stabilizer and adjunctive aripiprazole versus adjunctive olanzapine, quetiapine, risperidone or ziprasidone. RESEARCH DESIGN AND METHODS: A retrospective propensity score-matched cohort study was conducted in the LabRx integrated claims database from January 2003 to December 2006. Patients (18-65 years) with bipolar disorder and 180 days of pre-index enrolment without atypical treatment and 90 days post-index enrolment were eligible. Mood stabilizer therapy was initiated prior to index atypical prescription. Generalized gamma regressions were used to compare the total healthcare costs of adjunctive aripiprazole treatment and treatment with adjunctive olanzapine, quetiapine, risperidone or ziprasidone. RESULTS: After controlling for differences in baseline characteristics and pre-index cost, psychiatric costs and subtotal psychiatric and general medical costs were higher for all adjunctive atypicals than adjunctive aripiprazole (p<0.001). Based on gamma regressions cost ratios, there was no significant difference in general medical costs between aripiprazole and ziprasidone, olanzapine, or quetiapine; risperidone general medical costs were 18% higher versus aripiprazole (p=0.041). Aripiprazole pharmacy costs were higher than quetiapine and risperidone (p<0.001) but not olanzapine or ziprasidone. Total healthcare costs were higher for ziprasidone, olanzapine, or risperidone (p<0.001) but not quetiapine. LIMITATIONS: Methodological restriction of patients to those newly initiated on an atypical antipsychotic and incomplete medication history limit the generalizability of the findings. CONCLUSION: Adjunctive aripiprazole may have economic benefits over other atypicals in terms of lower psychiatric treatment costs than adjunctive olanzapine, quetiapine, risperidone or ziprasidone, and lower total healthcare costs than adjunctive olanzapine, risperidone or ziprasidone.

Drug safety surveillance in China and other countries: a review and comparison.

OBJECTIVES: Drug safety and postmarketing surveillance have become important public health issues in China. This study reviews the relatively new drug safety surveillance system in China and compares it with the systems in the United States and Europe. METHODS: An extensive literature review was conducted in the following four areas: 1) the organizational structure of the State Food and Drug Administration (SFDA) in China; 2) the development of an adverse drug reaction (ADR) monitoring system in China; 3) regulatory issues related to drug safety in China; and 4) similarities and differences between drug safety surveillance in China and surveillance in the United States and Europe. RESULTS: The SFDA oversees an extensive network of drug safety "watchdogs," including the China National Center for ADR Monitoring and 32 regional centers throughout China. China's system has faced a number of recent challenges. It has had to respond quickly to the withdrawal of various high-profile drugs like Vioxx (rofecoxib) and Baycol (cerivastatin) from other markets. Together with China's Ministry of Health, the SFDA has faced several unique drug safety events. Three of those events, involving the injectable form of the heartleaf houttuyinia herb (Yu Xing Cao), Armillarisni A injections, and clindamycin glucose infusions (Xinfu), are discussed. The rapid development of drug safety surveillance in China is manifested in extensive organizational structure, development of large databases, and laws and regulations supporting drug safety. The two major laws are the China Drug Administration Law issued in February 2001 and the Regulation for the Administration of ADR Reporting and Monitoring issued in March 2004. The study also discusses and compares recent developments in drug safety surveillance in the United States and the European Union. These developments will most likely have implications for the Chinese system in the near future. CONCLUSIONS: While postmarketing surveillance guidelines are not yet available in China, we fully expect their eventual issuance after adaptation to the particular culture and clinical practices in China.

Utilization, price, and spending trends for antidepressants in the US Medicaid Program.

BACKGROUND: Antidepressants are often used in the treatment of major depressive disorder and other mental illnesses, and constitute one of the most widely prescribed and costly medication classes in the US Medicaid Program. However, antidepressant utilization and price patterns within this market have not yet been adequately characterized. OBJECTIVES: This study was undertaken to analyze antidepressant drug utilization and price trends and to quantify market-share competition in Medicaid. METHODS: Quarterly utilization and payment data were retrieved from the national Medicaid pharmacy claims files provided by the Centers for Medicare & Medicaid Services. Quarterly per-prescription prices were estimated by dividing the payment amounts by the number of prescriptions. Descriptive time series analysis was conducted to assess the trends of utilization, expenditures, market shares, and prices from January 1991 through December 2005, for 3 major antidepressant subclasses--Selective Serotonin Reuptake Inhibitors (SSRIs), Tricyclic Antidepressants, and Other Antidepressants--as well as for individual agents within these subclasses. Using exponential smoothing models, 3-year market-share forecasts were produced. RESULTS: From 1991 to 2005, the total number of antidepressant prescriptions rose 380% from 6.82 million to 32.72 million. Total expenditures on antidepressants increased from $159 million in 1991 to $2.26 billion in 2004, then decreased to $1.99 billion in 2005, following the entry of lower-priced generic fluoxetine in 2001 and generic paroxetine in 2003. The payment market share for the SSRIs increased from 40% in 1991 to 82% in 1997, then decreased to 64% in 2005. It is projected to be 64% (95% confidence interval [CI]: 51-77%) in 2008 quarter 4. CONCLUSIONS: Increases in antidepressant drug expenditures were primarily because of rising utilization; however, there was also some increase in average price per prescription for many of the antidepressants studied. Switching to generic drugs may offer significant cost-saving potential.

Principal components analysis of drug expenditure and utilisation trends for major therapeutic classes in US Medicaid programmes.

OBJECTIVE: Drug expenditures have been increasing much faster than spending on other medical services and have become burdensome for state Medicaid programmes. The purpose of this study was to analyse these trends across major therapeutic classes and to identify their similarities and differences. METHODS: Using national claims data from the Centers for Medicare & Medicaid Services for 1991 quarter 1 through to 2004 quarter 4, expenditures and prescriptions were aggregated across all drugs in 64 different therapeutic classes, providing 128 (64 x 2) different time series, most of length 56 quarters. Principal components analysis (PCA) was then applied to the data. RESULTS: PCA revealed three principal components that accounted for 90% (92%) of total variation in Medicaid drug expenditure (utilisation) patterns. The first principal component (PC1), explaining 66% (67%) of the variation, is an exponential-like upward trend; PC2, explaining 17% (14%) of the variation, represents an increasing-then-decreasing pattern; and PC3, explaining 7% (11%) of the variation, represents an up-and-down cyclical pattern. Highly correlated with PC1 are antiretrovirals, antiseizure agents and corticoid steroids, among other drug classes. CONCLUSION: Most drug therapeutic classes exhibited exponential-like upward expenditure (and utilisation) trends, clearly illustrating the overall rising expenditure burden for Medicaid.

Utilization and spending trends for antiretroviral medications in the U.S. Medicaid program from 1991 to 2005.

BACKGROUND: HIV/AIDS incidence and mortality rates have decreased in the U.S. since 1996. Accompanying the longer life spans of those diagnosed with the disease, however, is a tremendous rise in expenditures on medication. The objective of this study is to describe the trends in utilization of, spending on, and market shares of antiretroviral medications in the U.S. Medicaid Program. Antiretroviral drugs include nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and fusion inhibitors (FIs). METHODS: Utilization and payment data from 1991 to 2005 are provided by the Centers for Medicare & Medicaid Services. Descriptive summary analyses were used to assess quarterly prescription numbers and amounts of payment. RESULTS: The total number of prescriptions for antiretrovirals increased from 168,914 in 1991 to 2.0 million in 1998, and 3.0 million in 2005, a 16.7-fold increase over 15 years. The number of prescriptions for NRTIs reached 1.6 million in 2005. Prescriptions for PIs increased from 114 in 1995 to 932,176 in 2005, while the number of prescriptions for NNRTIs increased from 1,339 in 1996 to 401,272 in 2005. The total payment for antiretroviral drugs in the U.S. Medicaid Program increased from US$ 30.6 million in 1991 to US$ 1.6 billion in 2005, a 49.8-fold increase. In 2005, NRTIs as a class had the highest payment market share. These drugs alone accounted for US$ 787.9 million in Medicaid spending (50.8 percent of spending on antiretrovirals). Payment per prescription for each drug, with the exception of Agenerase, increased, at least somewhat, over time. The relatively expensive drugs in 2005 included Trizivir ($1040) and Combivir ($640), as well as Reyataz ($750), Lexiva ($700), Sustiva ($420), Viramune ($370), and Fuzeon ($1914). CONCLUSION: The tremendous growth in antiretroviral spending is due primarily to rising utilization, secondarily to the entry of newer, more expensive antiretrovirals, and, finally, in part to rising per-prescription cost of existing medications.

Relationship of hospital-associated bleeding with length of stay and total hospitalization costs in patients hospitalized for atrial fibrillation.

BACKGROUND: While literature has focused on the impact of bleeding beginning outside the hospital setting among patients with atrial fibrillation (AF), there is little information regarding bleeding that first occurs within a hospital setting. This study was performed to determine the association between hospital-associated bleeding in patients admitted for AF on outcomes of length of stay (LOS) and total hospitalization cost. METHODS AND RESULTS: The Premier research database was queried to identify adult inpatients discharged between 2008-2011 having a primary diagnosis code for AF where a bleeding diagnosis code was not present on admission. Regression was used to adjust for baseline differences in patients to estimate outcomes comparing patients with and without a hospital-associated bleed. There were 143,287 patients that met the study criteria. There were 2991 (2.1%) patients identified with a hospital associated bleed. After adjustment for covariates, the mean estimated LOS was significantly greater in the bleed group, at 6.0 days (95% CI = 5.8-6.1) vs the no bleed group at 3.3 days (95% CI = 3.3-3.3) (p < 0.0001). Similarly, the adjusted mean estimated total hospitalization cost was also significantly greater in the bleed group, $12,069 (95% CI = $11,779-$12,366) vs $6561 (95% CI = $6538-$6583) in the no bleed group (p < 0.0001). CONCLUSIONS: After adjustments for baseline differences the data show that the 2.1% (n = 2991) of patients with hospital associated bleeding accounted for an estimated additional 8106 hospitalization days and $16.4 million dollars in cost over the study period compared to non-bleeders.

The impact of ribavirin on real-world adherence rates in hepatitis C patients treated with sofosbuvir plus simeprevir.

BACKGROUND: Combination therapy with sofosbuvir (SOF) and simeprevir (SIM) is used to treat patients with hepatitis C virus infection. It is currently unknown whether adding ribavirin (RBV) to SOF + SIM, which raises the pill count from two up to eight pills a day, impacts adherence. The aim of this study is to examine the impact of pill count on real-world adherence rates in patients treated with SOF + SIM with and without RBV. METHODS: This retrospective study assessed composite adherence to SOF and SIM over 12 weeks of treatment for two cohorts of hepatitis C patients: one initiating SOF + SIM therapy, and the other initiating SOF + SIM + RBV therapy. Analyses were conducted using MarketScan(®) and Optum US commercial pharmacy claims and enrollment data. Adherence was adjusted by treatment regimen, age, sex, co-pay, presence/absence of cirrhosis, treatment history, and Charlson Comorbidity Index. RESULTS: There was a significant difference in composite unadjusted and adjusted adherence rates for SOF and SIM for the SOF + SIM vs SOF + SIM + RBV cohorts based on MarketScan data (unadjusted, 92.6% and 89.7%, respectively; P=0.0423; adjusted, 92.2% and 88.7%, respectively; P=0.0176), but not based on Optum data (unadjusted, 94.8% and 95.6%, respectively; P=0.5618; adjusted, 94.8% and 95.1%, respectively; P=0.8589). In the MarketScan and Optum databases, there were no statistical differences in unadjusted and adjusted adherence rates for SOF. Unadjusted and adjusted adherence rates for SIM were mixed, as they were for composite adherence. CONCLUSION: The impact of the addition of RBV to SOF + SIM therapy was mixed. The impact of RBV on SOF adherence was not significant in either database.

Comparison of hospital length of stay between hospitalized non-valvular atrial fibrillation patients treated with either apixaban or warfarin.

BACKGROUND: Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared hospital LOS between hospitalized NVAF patients treated with either apixaban or warfarin. METHODS: This was a retrospective, observational cohort study based on a large US database including diagnosis, procedure, and drug administration information from >600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from 1 January 2013 to 28 February 2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. The study outcome was hospital LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated hospital LOS as discharge date minus first anticoagulant administration date. Sub-analyses were conducted among patients with a primary diagnosis of AF. RESULTS: The study included 832 apixaban patients matched to 832 warfarin patients. Mean [standard deviation (SD)] and median hospital LOS were significantly (p < 0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4). Results were consistent in the sensitivity and sub-analyses. CONCLUSIONS: Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These findings may have important clinical and economic implications for hospitals, payers, and patients.

Comparison of Medical Costs of Patients With Atrial Fibrillation Unsuitable for Warfarin Treatment With Apixaban or Aspirin Based on AVERROES Trial.

BACKGROUND: The AVERROES trial name is the following: The Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial demonstrated that apixaban reduced the risk of stroke relative to aspirin, without significantly increasing major bleeding risk in patients with atrial fibrillation (AF) considered unsuitable for warfarin therapy. Based on AVERROES trial results, this study compared the medical costs for clinical end points among patients with AF treated with either apixaban or aspirin. METHODS: Medical costs per patient-year for clinical events were determined. Based on clinical event rates for patients in the AVERROES trial, medical costs excluding drug costs were estimated for apixaban- and aspirin-treated patient groups. RESULTS AND CONCLUSIONS: Based on AVERROES trial results, among patients with AF unsuitable for warfarin therapy, apixaban use was estimated to be associated with a mean medical cost avoidance of US$735 in a patient-year relative to aspirin. The primary driver was the significant reduction in ischemic stroke rate. The medical cost reduction associated with apixaban use was consistent in sensitivity analyses.