Cost-Effectiveness Evaluation of Etoricoxib versus Celecoxib and Nonselective NSAIDs in the Treatment of Ankylosing Spondylitis in Norway

Objectives. To evaluate the cost-effectiveness of etoricoxib (90 mg) relative to celecoxib (200/400 mg), and the nonselective NSAIDs naproxen (1000 mg) and diclofenac (150 mg) in the initial treatment of ankylosing spondylitis in Norway. Methods. A previously developed Markov state-transition model was used to estimate costs and benefits associated with initiating treatment with the different competing NSAIDs. Efficacy, gastrointestinal and cardiovascular safety, and resource use data were obtained from the literature. Data from different studies were synthesized and translated into direct costs and quality adjusted life years by means of a Bayesian comprehensive decision modeling approach. Results. Over a 30-year time horizon, etoricoxib is associated with about 0.4 more quality adjusted life years than the other interventions. At 1 year, naproxen is the most cost-saving strategy. However, etoricoxib is cost and quality adjusted life year saving relative to celecoxib, as well as diclofenac and naproxen after 5 years of follow-up. For a willingness-to-pay ceiling ratio of 200,000 Norwegian krones per quality adjusted life year, there is a >95% probability that etoricoxib is the most-cost-effective treatment when a time horizon of 5 or more years is considered. Conclusions. Etoricoxib is the most cost-effective NSAID for initiating treatment of ankylosing spondylitis in Norway

Bayesian Meta-Analysis of Multiple Treatment Comparisons: An Introduction to Mixed Treatment Comparisons

AbstractRecently, mixed treatment comparisons (MTC) have been presented as an extension of traditional meta-analysis by including multiple different pairwise comparisons across a range of different interventions. MTC allow for indirect comparisons and can therefore provide very useful information for clinical and reimbursement decision-making in the absence of head-to-head data. In this article, we provide an introductory overview of MTC illustrated with example analyses of different drug treatments in rheumatoid arthritis using a continuous patient-reported end point. As a background, we start with an overview of the traditional meta-analyses for pairwise trials, and the difference between a traditional approach and a Bayesian approach. Next, the Bayesian MTC for continuous outcomes are presented. We finish with a discussion of how MTC can best be presented in order to maximize acceptance by target audiences, i.e., clinicians and market access decision-makers

R You Still Using Excel? The Advantages of Modern Software Tools for Health Technology Assessment

The Professional Society for Health Economics and Outcomes Research Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of health care resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research

Estimating marginal treatment effects from observational studies and indirect treatment comparisons: When are standardization-based methods preferable to those based on propensity score weighting?

In light of newly developed standardization methods, we evaluate, via simulation study, how propensity score weighting and standardization -based approaches compare for obtaining estimates of the marginal odds ratio and the marginal hazard ratio. Specifically, we consider how the two approaches compare in two different scenarios: (1) in a single observational study, and (2) in an anchored indirect treatment comparison (ITC) of randomized controlled trials. We present the material in such a way so that the matching-adjusted indirect comparison (MAIC) and the (novel) simulated treatment comparison (STC) methods in the ITC setting may be viewed as analogous to the propensity score weighting and standardization methods in the single observational study setting. Our results suggest that current recommendations for conducting ITCs can be improved and underscore the importance of adjusting for purely prognostic factors.Comment: 33 page

Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

Objective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC)-formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 mu g (n = 5 studies), indacaterol 300 mu g (n = 4), FOR/BUD 9/160 mu g (n = 2), FOR/BUD 9/320 mu g (n = 3), SAL/FP 50/500 mu g (n = 5), and SAL/FP 50/250 mu g (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.Results: Indacaterol 150 mu g resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 mu g (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 mu g (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 mu g (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 mu g (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 mu g at 12 weeks and indacaterol 150/300 mu g at 6 months. Indacaterol 150 mu g demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 mu g (-2.16 point improvement [-4.96, 0.95]). Indacaterol 150 and 300 mu g demonstrated comparable TDI scores versus SAL/FP 50/250 mu g (0.21 points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 mu g at 6 months.Conclusion: Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 mu g) and comparable to SAL/FP (50/250 and 50/500 mu g) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 mu g) and SAL/FP 50/500 mu g in terms of health status and to SAL/FP (50/250 and 50/500 mu g) in terms of breathlessness.Novartis Pharma AGMapi Values, Boston, MA 02114 USANovartis Pharma AG, Hlth Econ & Outcomes Res, Basel, SwitzerlandNovartis Horsham Res Ctr, Horsham, W Sussex, EnglandUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilWeb of Scienc

The cytocompatibility and early osteogenic characteristics of an injectable calcium phosphate cement.

In this study, the cytocompatibility and early osteogenic characteristics of rat bone marrow cells (RBMCs) on injectable calcium phosphate (CaP) cement (Calcibon) were investigated. In addition to unmodified CaP cement discs, 2 other treatments were given to the discs: preincubation in MilliQ and sintering at different temperatures. After primary culture, RBMCs were dropwise seeded on the discs and cultured for 12 days. The samples were evaluated in terms of cell viability, morphology (live and dead assays and scanning electron microscopy (SEM)), cell proliferation (deoxyribonucleic acid (DNA) analyses), early cell differentiation (alkaline phosphatase (ALP) activity), and physicochemical analyses (xray diffraction (XRD)). The live and dead, DNA, and SEM results showed that Calcibon discs without any additional treatment were not supporting osteoblast-like cells in vitro. There were fewer cells, and cell layers were detached from the disc surface. Therefore, different preincubation periods and sintering temperatures were evaluated to improve the cytocompatibility of the CaP cement. Preincubating discs in MilliQ for periods of 1, 4, 8, and 12 weeks resulted in the hydrolysis of a-tri calcium phosphate (TCP) into an apatite-like structure with some b-TCP, as shown with XRD, but the material was not cytocompatible. Sintering the discs between 8008C and 11008C resulted in conversion of a-TCP to b-TCP with some hydroxyapatite and an increase in crystallinity. Eventually, the discs sintered at 11008C achieved better cell attachment, more-abundant cell proliferation, and earlier differentiation than other sintered (6008C, 8008C, and 10008C), preincubated, and unmodified specimens. On basis of our results, we conclude that in vivo results with CaP-based cements do not guarantee in vitro applicability. Furthermore, unmodified Calcibon is not cytocompatible in vitro, although preincubation of the material results in a more-favorable cell response, sintering of the material at 11008C results in the best osteogenic properties. In contrast to in vivo studies, the Calcibon CaP cement is not suitable as a scaffold for cellbased tissue-engineering strategies

A cost-effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UK

Objective: To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK.Methods: The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data.Results: The caspofungin mean total treatment cost was £9762 (95% uncertainty interval 6955–12 577), which was £2033 (−2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 (−0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (£30 000). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings.Conclusion: Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK.<br/