Agnes Benedict

Overview of Parametric Survival Analysis for Health-Economic Applications

Health economic models rely on data from trials to project the risk of events (e.g., death) over time beyond the span of the available data. Parametric survival analysis methods can be applied to identify an appropriate statistical model for the observed data, which can then be extrapolated to derive a complete time-to-event curve. This paper describes the properties of the most commonly used statistical distributions as a basis for these models and describes an objective process of identifying the most suitable parametric distribution in a given dataset. The approach can be applied with both individual-patient data as well as with survival probabilities derived from published Kaplan–Meier curves. Both are illustrated with analyses of overall survival from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol trial.

An Economic Evaluation of Docetaxel and Paclitaxel Regimens in Metastatic Breast Cancer in the UK

AbstractBackground: Paclitaxel and docetaxel have been available for the treatment of metastatic breast cancer (MBC) since the 1990s. However, until very recently, comparisons between these two drugs have been difficult due to lack of direct comparative clinical evidence and differences in trial patient populations. Objective: To conduct a cost-effectiveness analysis comparing docetaxel with paclitaxel regimens in the treatment of MBC previously treated with an anthracycline from the perspective of the UK NHS. Methods: A cost-utility analysis was performed using a Markov model to compare taxanes in MBC patients who had progressed after treatment with an anthracycline-containing chemotherapy regimen: docetaxel 100 mg/m2 1-hour intravenous (IV) infusion every 21 days versus paclitaxel 175 mg/m2 3-hour IV infusion every 21 days (Pac3w). In parallel, additional analyses were performed versus paclitaxel administered in 1-weekly cycles (Pac1w), and a nano albumin-bound form of paclitaxel (Nab-P) given every 3 weeks. Progression-free survival (PFS), overall survival (OS) and adverse events used in the model were derived from a randomized trial directly comparing docetaxel with Pac3w; the comparisons of docetaxel versus the other two paclitaxel regimens were indirect, using patient-level data from a trial comparing Pac3w with Pac1w, and from the published literature comparing Pac3w with Nab-P. Utility values for response, progression and adverse events were derived from the literature.Direct treatment costs related to progression, best supportive care and adverse events were estimated using clinical trials data, published literature, NHS reference costs and published drug prices. The estimated costs of growth colony-stimulating factors and blood transfusion were also included in the model. The model was used to predict the expected total costs (£, year 2005–6 values), QALYs gained, incremental cost/life-year gained (LY) and cost/QALY over a 10-year time period. Results: In the base-case analysis, docetaxel improved QALYs by 0.33, 0.29 and 0.22 compared with Pac3w, Pac1w and Nab-P, respectively. The incremental cost-effectiveness ratios (ICERs) for docetaxel were £12 032/QALY versus Pac3w, £4583/QALY versus Pac1w and £14 694/QALY versus Nab-P. The ICER was sensitive to the hazard ratios for PFS and OS between the comparators, the drug cost of initial treatment and the treatment costs after progression. Taking into account parameter uncertainty, and comparing all four treatments simultaneously, at a willingness to pay of £20 000 per QALY gained, the probability of docetaxel being the most cost-effective treatment was around 70%. Conclusion: In the base-case scenario, docetaxel compared with Pac3w is estimated to have a cost-effectiveness ratio that falls within the acceptable threshold in the UK. The study also suggests that docetaxel may be cost effective versus Pac1w and Nab-P, although there is more uncertainty around these findings.

The Cost Effectiveness of Rufinamide in the Treatment of Lennox-Gastaut Syndrome in the UK

Background: Lennox-Gastaut syndrome (LGS) is a catastrophic childhood form of epilepsy. The syndrome is characterized bymental impairment, frequent seizures of multiple types that are particularly resistant to treatment, and high rates of seizure-related injury. With the introduction of newer, but more costly, antiepileptic drugs (AEDs), it is important that decision makers are able to assess their value in the management of this rare and difficult-to-treat condition.Objective: To evaluate the cost effectiveness, from the UK NHS perspective, of rufinamide in patients with LGS.Methods: An individual patient-simulation model was developed to estimate the total treatment-related costs and clinical benefits of rufinamide compared with topiramate and lamotrigine over a 3-year time horizon. The model examines the treatment scenarios of adding rufinamide, lamotrigine or topiramate to older AEDs (standard therapy), or standard therapy alone within a primary-care or community setting.Three placebo-controlled clinical trials of adjunctive AED treatment for children with LGS were analysed. There are no head-to-head comparator studies. Between 98 and 139 patients were randomized in each study and the mean age in each study was 10, 11 and 14 years. A mixed-treatment comparison using a random-effectsmodel was carried out on the number of patients in each response category, using the placebo arms of the respective trials. The primary outcome measure was the percentage of successfully treated patients, defined as >50% reduction in the frequency of total seizures and drop attacks. The hypothesis being tested was formulated after data collection.Costs (£, year 2006/07 values) of patient monitoring, switching treatments, hospitalization due to seizure, treatment of adverse effects, and personal and social services were included in the analysis. Results of 10 000 Monte Carlo simulations were bootstrapped to conduct probabilistic sensitivity analysis.Results: Over 3 years, adjunctive rufinamide resulted in higher total costs than topiramate and lamotrigine; however, with more patients being treated successfully, this leads to acceptable incremental cost-effectiveness ratios. If society is prepared to pay at least d250 for a 1% increase in the number of successfully treated LGS patients, in terms of a 50% reduction in the frequency of drop attacks, the probability of the treatment with rufinamide being cost effective is >80%.Conclusion: This cost-effectiveness analysis suggests that rufinamide results in more LGS patients being treated successfully at a reasonable cost from a UK NHS perspective.

Simulation and Matching-Based Approaches for Indirect Comparison of Treatments

Estimates of the relative effects of competing treatments are rarely available from head-to-head trials. These effects must therefore be derived from indirect comparisons of results from different studies. The feasibility of comparisons relies on the network linking treatments through common comparators; the reliability of these may also be impacted when the studies are heterogeneous or when multiple intermediate comparisons are needed to link two specific treatments of interest. Simulated treatment comparison and matching-adjusted indirect comparison have been developed to address these challenges. These focus on comparisons of outcomes for two specific treatments of interest by using patient-level data for one treatment (the index) and published results for the other treatment (the comparator) from compatible studies, taking into account possible confounding due to population differences. This paper provides an overview of how and when these approaches can be used as an alternative or to complement standard MTC approaches.

Cost-Effectiveness Analysis of Anastrozole versus Tamoxifen in Adjuvant Therapy for Early-Stage Breast Cancer - a Health-Economic Analysis Based on the 100-Month Analysis of the ATAC Trial and the German Health System

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a significantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 (

Quality of life and drug costs associated with switching antipsychotic medication to once-daily extended release quetiapine fumarate in patients with schizophrenia

30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen.

Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective

ABSTRACT Objective: The objective of this study was to assess the quality of life and drug costs associated with switching from any ongoing antipsychotic treatment to once-daily extended release quetiapine fumarate (quetiapine XR) in patients with schizophrenia. Methods: This assessment was based on data collected during a 12-week study in patients with schizophrenia (n = 477) who switched from their current antipsychotic due to insufficient efficacy or poor tolerability to a flexible dose of quetiapine XR. Patients were assigned utilities based on their Positive and Negative Syndrome Scale (PANSS) scores and the presence of adverse events by applying the methods of Lenert et al.1. Quality adjusted life year (QALY) gains were calculated assuming a linear change of utility between two consecutive visits. Incremental costs were calculated by comparing the hypothetical mean drug cost (assuming patients stay on previous treatment) with the actual mean cost of quetiapine XR based on European prices. Results: Patients who completed the study (n = 279) increased their average utility by 0.116, corresponding to a QALY gain of 0.0207. For the total sample, the mean utility increased by 0.09, reflecting a QALY gain of 0.0170. The additional costs for quetiapine XR per QALY gained varied from approximately €16,000 to €24,000. Notably, this is a non-comparative study; therefore, no conclusions can be reached regarding the relative impact of switching to quetiapine XR compared with other antipsychotics. Further limitations included the short trial duration on which the utility estimates are based, and the restriction of cost data to drug costs alone. Furthermore, in a ‘real world’ scenario, it is to be expected that other drug regimens might be introduced during periods of treatment failure. Conclusion: This analysis demonstrates that patients with schizophrenia who switch their antipsychotic medication to quetiapine XR because of insufficient efficacy or poor tolerability benefit from significant QALY gains at a reasonable increase in drug cost.

Potential economic impact of increasing low dose aspirin usage on CVD in the US

Abstract Objective: To assess the economic value of carfilzomib (Kyprolis), this study developed the Kyprolis Global Economic Model (K-GEM), which examined from a United States (US) payer perspective the cost-effectiveness of carfilzomib-lenalidomide-dexamethasone (KRd) versus lenalidomide-dexamethasone (Rd) in relapsed multiple myeloma (RMM; 1–3 prior therapies) based on results from the phase III ASPIRE trial that directly compared these regimens. Methods: A partitioned survival model that included three health states of progression-free (on or off treatment), post-progression, and death was developed. Using ASPIRE data, the effect of treatment regimens as administered in the trial was assessed for progression-free survival and overall survival (OS). Treatment effects were estimated with parametric regression models adjusting for baseline patient characteristics and applied over a lifetime horizon. US Surveillance, Epidemiology and End Results (1984–2014) registry data were matched to ASPIRE patients to extrapolate OS beyond the trial. Estimated survival was adjusted to account for utilities across health states. The K-GEM considered the total direct costs (pharmacy/medical) of care for patients treated with KRd and Rd. Results: KRd was estimated to be more effective compared to Rd, providing 1.99 life year and 1.67 quality-adjusted life year (QALY) gains over the modeled horizon. KRd-treated patients incurred

Model-Based Cost-Effectiveness Analyses for the Treatment of Chronic Myeloid Leukaemia: A Review and Summary of Challenges

179,393 in total additional costs. The incremental cost-effectiveness ratio (ICER) was

Modelling survival in hepatocellular carcinoma

107,520 per QALY. Limitations: Extrapolated survival functions present the greatest uncertainty in the modeled results. Utilities were derived from a combination of sources and assumed to reflect how US patients value their health state. Conclusions: The K-GEM showed KRd is cost-effective, with an ICER of