Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States.

INTRODUCTION: While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective. METHODS: We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs. CONCLUSION: Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

Cost-effectiveness of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

[Mirabegron, a breakthrough in overactive bladder syndrome?] / Mirabegrón ¿un avance en el síndrome de vejiga hiperactiva?

OBJECTIVE: Overactive bladder syndrome is a condition with high prevalence, which has a negative impact on patients' quality of life. A drug with a novel mechanism of action has been recently approved: mirabegron. The objective of this study is to review the scientific evidence available on mirabegron, with the aim to analyze its efficacy, safety and cost, and thus estimate its role within current pharmacotherapy. Methods: The effectiveness and safety of mirabegron were analyzed through an evaluation of scientific evidence. The cost of different pharmacological alternatives was calculated based on their Defined Daily Dose (DDD) and their manufacturer's sale price. Results: The use of mirabegron in the treatment of overactive bladder syndrome is supported by three randomized clinical trials, controlled with placebo, at 12 weeks. All three share the same primary efficacy variables (number of incontinence episodes per 24 hours and number of micturitions per 24 hours). Long-term efficacy data are based on a 12-month study, where efficacy outcomes were measured as secondary variables. In all studies, mirabegron showed a significant but modest effect. Some of the most frequently detected adverse effects were: hypertension, increase of glucose in blood, headache, urinary tract infections, constipation and tachycardia. Special attention must be paid to cardiovascular events. Conclusions: The clinical efficacy of mirabegron is very modest and comparable to that achieved with the other drugs approved for this indication. Moreover, it is more expensive than other therapeutic options. Cardiac risks and urinary infections only allow to consider it as an alternative option to anticholinergic drugs, when these are contraindicated, show no clinical efficacy, or cause unacceptable adverse effects.

Objetivo: El síndrome de vejiga hiperactiva es una patología con elevada prevalencia y que tiene un impacto negativo sobre la calidad de vida de los pacientes. Recientemente se ha aprobado un fármaco con un novedoso mecanismo de acción: el mirabegrón. El objetivo de este estudio es revisar la evidencia científica disponible sobre el mirabegrón, con el fin de analizar su eficacia, seguridad y coste, y así estimar su papel en la farmacoterapia actual.Metodología: La eficacia y seguridad del mirabegrón se analizó mediante una evaluación de la evidencia científica. El coste de las diferentes alternativas farmacológicas se calculó en base a sus dosis diarias definidas (DDD) y el precio de venta del laboratorio. Resultados: Tres ensayos clínicos aleatorizados, controlados con placebo, de 12 semanas de duración, apoyan el uso del mirabegrón en el tratamiento del síndrome de vejiga hiperactiva. Los tres comparten las mismas variables principales de eficacia (número de episodios de incontinencia/24 h y número de micciones/24 h). Los datos de eficacia a largo plazo se basan en un estudio de seguridad de 12 meses de duración en el que los resultados de eficacia se medían como variables secundarias. En todos los estudios, el mirabegrón mostró un efecto significativo pero modesto. Entre los efectos adversos más frecuentes se detectaron hipertensión, aumento de glucosa en sangre, dolor de cabeza, infecciones del tracto urinario, estreñimiento y taquicardia. Se debe prestar especial atención a los eventos cardiovasculares. Conclusiones: La eficacia clínica del mirabegrón es muy modesta y comparable a la conseguida con el resto de fármacos aprobados para esta indicación. Además, presenta un mayor coste que otras alternativas terapéuticas. Los riesgos cardiacos e infecciones urinarias solo hacen posible considerarlo como  una alternativa a los anticolinérgicos cuando estos estén contraindicados, sean clínicamente ineficaces o sus efectos adversos sean inaceptables.

Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation at high risk of bleeding and normal kidney function.

INTRODUCTION: The comparative cost-effectiveness of all oral anticoagulants approved up to date has not been evaluated from the US perspective. The objective of this study was to compare the cost-effectiveness of edoxaban 60mg, apixaban 5mg, dabigatran 150mg, dabigatran 110mg, rivaroxaban 20mg and warfarin in stroke prevention in atrial fibrillation patients at high-risk of bleeding (defined as HAS-BLED score≥3). MATERIALS AND METHODS: We constructed a Markov state-transition model to evaluate lifetime costs and quality-adjusted life years (QALYs) with each of the six treatments from the perspective of US third-party payers. Probabilities of clinical events were obtained from the RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF-TIMI trials; costs were derived from the Healthcare Cost and Utilization Project, and other studies. Because edoxaban is only indicated in patients with creatinine clearance ≤95ml/min, we re-ran our analyses after excluding edoxaban from the analysis. RESULTS: Treatment with edoxaban 60mg cost $77,565/QALY gained compared to warfarin, and apixaban 5mg cost $108,631/QALY gained compared to edoxaban 60mg. When edoxaban was not included in the analysis, treatment with apixaban 5mg cost $84,128/QALY gained, compared to warfarin. Dabigatran 150mg, dabigatran 110mg and rivaroxaban 20mg were dominated strategies. CONCLUSIONS: For patients with creatinine clearance between 50 and 95ml/min, apixaban 5mg was the most cost-effective treatment for willingness-to-pay thresholds (WTP) above $115,000/QALY gained, and edoxaban 60mg was cost-effective when the WTP was between $75,000 and $115,000/QALY gained. For patients with creatinine clearance >95ml/min, apixaban 5mg was the most cost-effective treatment for WTP thresholds above $80,000/QALY gained.

Estimated Budget Impact of Increased Use of Mirabegron, A Novel Treatment for Overactive Bladder.

BACKGROUND: Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB. OBJECTIVE: To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model. METHODS: For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables. RESULTS: Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model. CONCLUSIONS: Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs. DISCLOSURES: Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.

Cost-Effectiveness of High-Dose Edoxaban Compared with Adjusted-Dose Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation Patients.

OBJECTIVE: To estimate the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of high-dose edoxaban compared with adjusted-dose warfarin in patients at risk for stroke who have nonvalvular atrial fibrillation (NVAF) and a creatinine clearance (Clcr ) of 15-95 ml/minute. METHODS: A Markov model was created to compare the cost-effectiveness of high-dose edoxaban and adjusted-dose warfarin in patients with a Clcr of 15-95 ml/minute. The model was performed from a U.S. societal perspective and assumed patients initiated therapy at 70 years of age, had a mean CHADS2 (congestive heart failure, hypertension, age 75 or older, diabetes, stroke) score of 3, and no contraindications to anticoagulation. The model assumed a cycle length of 1 month and a lifetime horizon (maximum of 30 years/360 cycles). Data sources included renal subgroup analysis of the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE-AF) trial and other published studies. Outcomes included lifetime costs (2014 US$), QALYs, and incremental cost-effectiveness ratios. The robustness of the model's conclusions was tested using one-way and 10,000-iteration probabilistic sensitivity analysis (PSA). RESULTS: Patients treated with high-dose edoxaban lived an average of 10.50 QALYs at a lifetime treatment cost of $99,833 compared with 10.11 QALYs and $123,516 for those treated with adjusted-dose warfarin. The model's conclusions were found to be robust upon one-way sensitivity analyses. PSA suggested high-dose edoxaban was economically dominant compared with adjusted-dose warfarin in more than 99% of the 10,000 iterations run. CONCLUSIONS: High-dose edoxaban appears to be an economically dominant strategy when compared with adjusted-dose warfarin for the prevention of stroke in NVAF patients with a Clcr of 15-95 ml/minute and an appreciable risk of stroke.

Non-vitamin K Oral Anticoagulants Versus Warfarin for Patients with Atrial Fibrillation: Absolute Benefit and Harm Assessments Yield Novel Insights.

BACKGROUND AND OBJECTIVES: Benefits and/or harms (including costs) of non-vitamin K oral anticoagulants (NOACs) versus warfarin therapy need appreciation in relative and absolute terms. METHODS: Accordingly, we derived clinically relevant relative and absolute benefit/harm parameters for NOACs (apixaban, dabigatran, rivaroxaban, edoxaban) compared to warfarin from four clinical trials involving atrial fibrillation (AF) patients. For each trial, we tabulated patient numbers enduring four important outcomes and calculated unadjusted relative risk reduction (RRR) and number needed to treat (NNT)/year values (and 95% confidence intervals) for the NAOC compared to warfarin. These outcomes were as follows: stroke/systemic embolism (primary endpoint), hemorrhagic stroke, major bleeds, and death. We also addressed drug acquisition costs. RESULTS: Each NOAC was noninferior to warfarin for primary-outcome prevention; RRRs were 12-33% and NNT/year values were 182-481, and all but one indicated statistically significant superiority. All the NOACs yielded statistically significant reductions in hemorrhagic stroke risk; RRRs were 42-74% and NNT/year values were 364-528. Major bleeding risk was comparable in both groups. Apixaban yielded a lower NNT/year for preventing death than for primary-outcome prevention. Compared to warfarin, NOAC acquisition costs were 70- to 140-fold greater. CONCLUSIONS: For the primary outcome, the absolute benefits of NOACs were modest (NNT/year values being large). Reduced hemorrhagic stroke rates with NOACs could be due to superior embolic infarct prevention and fewer consequential hemorrhagic transformations. Among apixaban recipients, the absolute mortality benefit exceeded that for the primary outcome, indicating prevention of additional unrelated deaths. The substantially greater NOAC acquisition costs need viewing against probable greater safety and the avoidance of monitoring bleeding risks.

Edoxaban: a review in nonvalvular atrial fibrillation.

The factor Xa inhibitor edoxaban (Lixiana(®)) is a new direct oral anticoagulant recently approved in the EU for the prevention of stroke and systemic embolic events (SEE) in patients with nonvalvular atrial fibrillation and one or more risk factors. In the large, randomized, double-blind, double-dummy, ENGAGE AF-TIMI 48 trial, oral edoxaban dosages of 30 and 60 mg once daily for a median treatment duration of 907 days in patients with moderate-to-high-risk nonvalvular atrial fibrillation were noninferior to warfarin for the incidence of first stroke or SEE. Both high-dose and low-dose edoxaban were associated with significantly lower rates than warfarin of major bleeding, including intracranial haemorrhage, and death from cardiovascular causes. Edoxaban has a rapid onset of action, a short half-life, few drug interactions and offers the convenience of oral, once-daily, fixed-dose administration, without the need for coagulation monitoring and without regard to food. Therefore, edoxaban is an effective and well tolerated therapeutic option in patients with nonvalvular atrial fibrillation.

Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US.

OBJECTIVE: Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined. METHODS: Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018. RESULTS: In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018. CONCLUSIONS: Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Economic evaluation of pharmacological treatments for overactive bladder from the perspective of the UK National Health Service.

OBJECTIVE: To evaluate the costs and outcomes associated with different sequences of oral anti-muscarinic agents and the selective ß(3)-adrenoceptor agonist, mirabegron, for the treatment of overactive bladder (OAB). METHODS: A Markov model with monthly cycle length and time horizon up to 3 years was designed to compare two different sequences of up to three lines of oral therapy for OAB. Patients who discontinued one oral medication could switch to another oral medication or could discontinue treatment. Patients whose symptoms were not controlled were considered for botulinum toxin or sacral nerve stimulation. Outcomes were measured by (a) number of patients with controlled symptoms (no incontinence episodes and <8 micturitions per 24 h); (b) patients with no incontinence episodes per 24 hours; and (c) patients with <8 micturitions per 24 h. RESULTS: Including a third-line oral medication before considering other treatment options improved all patient outcomes, irrespective of the specific drugs used. A three-line sequence including two generic (oxybutynin first line and tolterodine extended-release second line) and one branded drug (solifenacin 5 mg third line) resulted in inferior patient outcomes at costs similar to a sequence of branded drugs (mirabegron first line, solifenacin 5 mg second line, solifenacin 10 mg third line): controlled patients (generic 29.6/1000 vs branded 38.7/1000); patients with no incontinence episodes (103.6/1000 vs 123.7/1000); patients with <8 micturitions (228.7/1000 vs 262.1/1000). Annual treatment costs per patient were similar (generic £1299 vs branded £1385). CONCLUSIONS: In the treatment of OAB, low-cost generic treatments are not necessarily more cost-effective than branded drugs, primarily because a better efficacy and tolerability balance improves both symptom control and persistence.

Evaluation of medical costs associated with use of new oral anticoagulants compared with standard therapy among venous thromboembolism patients.

OBJECTIVE: This study evaluated differences in medical costs associated with clinical end-points from randomized clinical trials that compared the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, to standard therapy for treatment of patients with venous thromboembolism (VTE). RESEARCH DESIGN AND METHODS: Event rates of efficacy and safety end-points from the clinical trials (RE-COVER, RE-COVER II, EINSTEIN-Pooled, AMPLIFY, Hokusai-VTE trial) 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 end-points for the NOACs vs standard therapy were then estimated. One-way and Monte Carlo sensitivity analyses were carried out. RESULTS: A lower rate of major bleedings was associated with use of any of the NOACs vs standard therapy. Except for dabigatran, use of NOACs was also associated with a lower rate of recurrent VTE/death. As a result of the reduction in clinical event rates, the overall medical cost differences were -$146, -$482, -$918, and -$344 for VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, vs patients treated with standard therapy. CONCLUSIONS: When any of the four NOACs are used instead of standard therapy for acute VTE, treatment medical costs are reduced. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety end-points. Further evaluation may be needed to validate these results in the real-world setting.

Cost-effectiveness of novel therapies for overactive bladder.

Overactive bladder is a difficult to treat condition affecting a large proportion of adults resulting in considerable economic impact to society. First-line treatments such as behavioral therapy or antimuscarinic medication are frequently not effective in adequately controlling symptoms or have intolerable side effects. Patients subsequently require second-line therapy including, sacral neuromodulation through either posterior tibial nerve stimulation or sacral nerve stimulation or intra-detrusor injection of Onabotulinumtoxin-A. Mirabegron, a relatively new drug in a separate class, is also employed in the treatment of overactive bladder. The question of which novel therapy to initiate depends on several factors including patient preference, effectiveness and cost. The purpose of this review is to present and discuss the most recent studies pertaining to the cost-effectiveness of novel therapies for overactive bladder.

Cost-effectiveness of febuxostat in chronic gout.

Our objective was to evaluate data on the cost-effectiveness of febuxostat compared with standard clinical practice with allopurinol in patients with gout that was presented to the Scottish Medicines Consortium (SMC) in 2010. A Markov health-state model estimated the direct health-related costs and clinical benefits expressed as quality-adjusted life-years (QALYs). Adults with chronic gout and established hyperuricaemia received treatment sequences of daily doses of allopurinol 300 mg alone or allopurinol 300 mg followed by febuxostat 80 mg/120 mg. The proportion of patients achieving the target serum uric acid (sUA) level of less than 6 mg/dl (0.36 mmol/l) was linked to the utility per sUA level to generate an incremental cost-effectiveness ratio (ICER). Second-line therapy with febuxostat 80 mg/120 mg versus with allopurinol alone resulted in an ICER of £3,578 per QALY over a 5-year time horizon. Additional univariate analyses showed that ICER values were robust and ranged from £2,550 to £7,165 per QALY when different parameters (e.g., low- and high-dose allopurinol titrations and variations in treatment-induced flare rates) were varied. Febuxostat reduces sUA below the European League Against Rheumatism target of 0.36 mmol/l (6 mg/dl) in significantly more patients with gout than allopurinol in its most frequently prescribed dose of 300 mg per day. The SMC accepted febuxostat as cost-effective as a suitable second-line option for urate-lowering therapy for the treatment of patients with chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history or presence of tophus and/or gouty arthritis) when treatment with allopurinol was inadequate, not tolerated, or contraindicated.

An efficient and economical MTT assay for determining the antioxidant activity of plant natural product extracts and pure compounds.

Antioxidants scavenge free radicals, singlet oxygen, and electrons in cellular redox reactions. The yellow MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] is reduced to a purple formazan by mitochondrial enzymes. NADPH is the basis of established in vitro cell viability assays. An antioxidant assay has been developed utilizing the redox reaction between MTT and selected natural product extracts and purified compounds. This simple, fast, and inexpensive MTT antioxidant assay is comparable with the lipid peroxidation inhibitory assay and can be mechanized to achieve high throughput.

Modelling therapeutic strategies in the treatment of osteoarthritis: an economic evaluation of meloxicam versus diclofenac and piroxicam.

OBJECTIVE: To assess the economic efficiency of meloxicam, a cyclo-oxygenase (COX)-2 selective inhibitor, versus diclofenac and piroxicam in the UK for the treatment of patients with osteoarthritis and the impact on the NHS budget of substituting nonselective NSAIDs with meloxicam. Methods and perspective: A decision analytical model was used to compare the effects of 4 weeks' treatment of osteoarthritis with meloxicam (7.5 mg/day), diclofenac (100 mg/day) and piroxicam (20 mg/day). The decision tree was derived by combining best practice and clinical reality. Analysis was from the NHS perspective. The study considered only the direct costs. These included costs for drug acquisition and management of all adverse events, both serious gastrointestinal events requiring hospitalisation, and non-serious events that required maintenance. Resource use and treatment costs were obtained from local and published sources. A range of sensitivity analyses was carried out. RESULTS: Based on two 4-week large-scale trials, the Meloxicam Large-scale International Study Safety Assessment (MELISSA) and Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trials, and a decision analytical model, the findings suggested that meloxicam had the lowest cost per patient ( pound 30 versus pound 35 for piroxicam and pound 51 for diclofenac [costs presented as 1998 values except for drug costs which were in 2000 values]). The results of the Monte Carlo probabilistic sensitivity analysis, using 4000 samples, suggested that meloxicam was the optimal strategy in the drug treatment of patients with osteoarthritis compared with nonselective NSAIDs both individually and as a group. The cost savings were due to lower levels of serious adverse events accompanied by fewer days in intensive care units and shorter overall duration of hospital stay observed with meloxicam compared with diclofenac and piroxicam in the 4-week trials. CONCLUSIONS: Based on the 4-week trial period, meloxicam was predicted to be the lowest cost drug therapy, and thus the optimal drug therapy, in the management of patients with osteoarthritis compared with nonselective NSAIDs such as diclofenac and piroxicam. Applying the cost savings per patient derived from the model, switching patients from piroxicam and diclofenac to meloxicam would indicate a cost saving of over pound 25 million per annum. Models such as this can facilitate better clinical guidance and is a useful way of assessing treatment outcomes.