Methodologies used in cost-effectiveness models for evaluating treatments in major depressive disorder: a systematic review

<p>Abstract</p> <p>Background</p> <p>Decision makers in many jurisdictions use cost-effectiveness estimates as an aid for selecting interventions with an appropriate balance between health benefits and costs. This systematic literature review aims to provide an overview of published cost-effectiveness models in major depressive disorder (MDD) with a focus on the methods employed. Key components of the identified models are discussed and any challenges in developing models are highlighted.</p> <p>Methods</p> <p>A systematic literature search was performed to identify all primary model-based economic evaluations of MDD interventions indexed in MEDLINE, the Cochrane Library, EMBASE, EconLit, and PsycINFO between January 2000 and May 2010.</p> <p>Results</p> <p>A total of 37 studies were included in the review. These studies predominantly evaluated antidepressant medications. The analyses were performed across a broad set of countries. The majority of models were decision-trees; eight were Markov models. Most models had a time horizon of less than 1 year. The majority of analyses took a payer perspective. Clinical input data were obtained from pooled placebo-controlled comparative trials, single head-to-head trials, or meta-analyses. The majority of studies (24 of 37) used treatment success or symptom-free days as main outcomes, 14 studies incorporated health state utilities, and 2 used disability-adjusted life-years. A few models (14 of 37) incorporated probabilities and costs associated with suicide and/or suicide attempts. Two models examined the cost-effectiveness of second-line treatment in patients who had failed to respond to initial therapy. Resource use data used in the models were obtained mostly from expert opinion. All studies, with the exception of one, explored parameter uncertainty.</p> <p>Conclusions</p> <p>The review identified several model input data gaps, including utility values in partial responders, efficacy of second-line treatments, and resource utilisation estimates obtained from relevant, high-quality studies. It highlighted the differences in outcome measures among the trials of MDD interventions, which can lead to difficulty in performing indirect comparisons, and the inconsistencies in definitions of health states used in the clinical trials and those used in utility studies. Clinical outcomes contributed to the uncertainty in cost-effectiveness estimates to a greater degree than costs or utility weights.</p

Cost/effectiveness model of dabigatran in the prevention of venous thromboembolism in major orthopedic surgery: Adaptation for Italy

Venous thromboembolic events (VTE) represent a dangerous complication of major orthopedic surgery, especially in total hip replacement (THR) and total knee replacement (TKR) procedures. Dabigatran etexilate (DBG), a direct and reversible thrombin inhibitor, has proven its non-inferiority with respect to enoxaparin 40mg once-daily, a low molecular weight heparin (LMWH), in the prevention of VTE in patients undergoing THR and TKR, in the RE-NOVATE and RE-MODEL trials, respectively. The objective of this analysis was to estimate cost/effectiveness and cost/utility of DBG compared to standard care for the prevention of VTE in Italy. A decision analytic, Markov-chain based model, originally developed for the UK, was adapted to the Italian context. The adaptation involved cost and demographic characteristics, clinical and utility data were not altered. Costs were taken from national observational studies, where available. Otherwise, current prices and tariffs were applied. Resource consumption was derived from practice guidelines or taken from the UK model. According to the prevalent national practice, extended prophylaxis is considered for both surgical procedures. The time horizon of the analysis was patients’ lifetimes. In order to consider different alternatives for drug dispensation and, consequently, National Health Service acquisition costs, alternative scenarios were developed. A further scenario, excluding LMWHs administration costs (“worst-case” scenario), was considered. Compared to LMWHs, DBG was associated with an expected increase of 0.019 life-years (LYs) and 0.014 quality-adjusted life-years (QALYs) per THR patient and of 0.024 LYs and 0.019 QALYs per TKR patient. DBG-related costs were lower than LMWH in both procedures, with a mean difference ranging from 89 to 116 € for THR, and 107 to 142 for TKR, depending on the LMWH product. Higher acquisition costs for DBG were completely offset and inverted by avoided administration expenses and, to a lesser extent, by savings in VTE management. The results of alternative scenarios confirm the dominance of DBG, with a net saving ranging between 119 €, when both drugs were obtained by auction, and 32 €, when the auction price was applied but DBG was dispensed through territorial pharmacies. The corresponding estimates for TKR were 148 and 54 €. In the “worst-case” scenario, DBG was no longer dominant, with a cost per LYs of 2,788 and 4,514 € and a cost per QALY gained of 3,619 and 5,926 €, for TKR and THR respectively. In conclusion, DBG dominated LMWHs, and was cost-saving and non-inferior in terms of efficacy and safety, except for in the “worst-case” scenario, in which the incremental cost/effectiveness ratio estimate was lower than commonly accepted thresholds in health economics

Cost Effectiveness of Pegaptanib for the Treatment of Age-Related Macular Degeneration in the UK

Background: Age-related macular degeneration (AMD) is the primary cause of vision loss in the elderly and results in significant economic and humanistic burden. The selective vascular endothelial growth factor inhibitor, pegaptanib (Macugen(R)) is indicated for patients with neovascular AMD. Guidance is needed regarding the cost effectiveness of treatment, any variation between sub-populations of differing clinical characteristics and the optimum duration of treatment. Objective: To estimate the cost effectiveness of pegaptanib versus best supportive care (BSC) for AMD from the perspective of the UK government, and to evaluate the impact of patient characteristics and differing treatment discontinuation scenarios. Methods: A cohort of 1000 patients aged >45 years with a best-corrected visual acuity (VA) in their better-seeing eye of =6 lines. The IC/QALY was estimated as Lstg 8023 (upper 95% CI Lstg 20_641). Cost effectiveness varied by age (age =75 years = Lstg 11_657/QALY) and by pre-treatment VA (6/12-6/95 = Lstg 8023/QALY; 6/12-6/60 = Lstg 6664/QALY; 6/12-6/24 = Lstg 1920/QALY). Gender and lesion type or size had little effect. Cost effectiveness was not sensitive to precise rules for treatment discontinuation, but was maximised if treatment was discontinued in patients no longer likely to benefit. Conclusions: The results suggest that pegaptanib treatment is likely to be cost effective across all groups studied, and marginally more cost effective in younger patients and those with better pre-treatment VA. Cost effectiveness appears to be optimised if treatment is discontinued after 1 year if individual patients' VA has dropped by >=6 lines from pre-treatment levels, or at any time if it drops below 6/95. However, strict application of discontinuation rules does not appear to be necessary for pegaptanib to be cost effective. Clinical judgement and patient preference should be an important determinant in decisions about stopping treatment.Age-related-macular-degeneration, Cost-utility, Pegaptanib

Cost-Effectiveness of Olaratumab in Combination with Doxorubicin for Patients with Soft Tissue Sarcoma in the United States

Background. Standard first-line treatments for advanced soft tissue sarcoma (STS) have changed little for 40 years, and outcomes have been poor. Recently, the United States (US) Food and Drug Administration conditionally approved olaratumab in combination with doxorubicin (Olara + Dox) based on a randomized phase II trial that reported a significant 11.8-month improvement in median survival versus single-agent doxorubicin (Dox). The present study investigated the cost-effectiveness of Olara + Dox compared with Dox and five other standard-of-care regimens from the US payer perspective. Methods. An economic model was constructed to estimate costs and outcomes over patients’ lifetimes from start of therapy. Progression-free and overall survival were based on survival analysis of patient-level data and a meta-analysis. Adverse-event rates were based on trials. Costs were from published sources. Results. Olara + Dox resulted in an estimated additional 1.27 life-years (LYs) compared with Dox, with an increase in total expected lifetime costs of $133,653. The incremental cost-effectiveness ratio (ICER) was estimated at$105,408 per LY gained; in a fully incremental analysis, all other regimens were dominated (higher costs and lower LYs or a higher ICER). Conclusion. Olara + Dox is cost-effective for STS treatment compared with Dox and other standard-of-care regimens at willingness-to-pay thresholds of $150,000 per LY and above