Development of a population-based microsimulation model of osteoarthritis in Canada.

OBJECTIVES: The purpose of the study was to develop a population-based simulation model of osteoarthritis (OA) in Canada that can be used to quantify the future health and economic burden of OA under a range of scenarios for changes in the OA risk factors and treatments. In this article we describe the overall structure of the model, sources of data, derivation of key input parameters for the epidemiological component of the model, and preliminary validation studies. DESIGN: We used the Population Health Model (POHEM) platform to develop a stochastic continuous-time microsimulation model of physician-diagnosed OA. Incidence rates were calibrated to agree with administrative data for the province of British Columbia, Canada. The effect of obesity on OA incidence and the impact of OA on health-related quality of life (HRQL) were modeled using Canadian national surveys. RESULTS: Incidence rates of OA in the model increase approximately linearly with age in both sexes between the ages of 50 and 80 and plateau in the very old. In those aged 50+, the rates are substantially higher in women. At baseline, the prevalence of OA is 11.5%, 13.6% in women and 9.3% in men. The OA hazard ratios for obesity are 2.0 in women and 1.7 in men. The effect of OA diagnosis on HRQL, as measured by the Health Utilities Index Mark 3 (HUI3), is to reduce it by 0.10 in women and 0.14 in men. CONCLUSIONS: We describe the development of the first population-based microsimulation model of OA. Strengths of this model include the use of large population databases to derive the key parameters and the application of modern microsimulation technology. Limitations of the model reflect the limitations of administrative and survey data and gaps in the epidemiological and HRQL literature.

The comparative responsiveness of the EQ-5D and SF-6D to change in patients with inflammatory arthritis.

PURPOSE: Comparative evidence regarding the responsiveness of the EQ-5D and SF-6D in arthritis patients is conflicting and insufficient across the range of disease severity. We examined the comparative responsiveness of the EQ-5D and SF-6D in cohorts of patients with early inflammatory disease through to severe rheumatoid arthritis (RA). METHODS: Responsiveness was tested using the effect size (ES) and standardised response mean (SRM). Correlation of change in EQ-5D and SF-6D with disease specific measures was tested using Pearson correlations and the Steiger's Z test. Treatment response and self-reported change were used as anchors of important change. RESULTS: The EQ-5D was more responsive to deterioration (ES ratio (EQ-5D/SF-6D): 1.6-3.0) and the SF-6D more responsive to improvement (ES ratio (SF-6D/EQ-5D): 1.1-1.8) in health. The SF-6D did not respond well to deterioration in patients with established severe RA (ES and SRM 0.08). The EQ-5D provided larger absolute mean change estimates but with greater variance compared to the SF-6D. CONCLUSIONS: The comparative responsiveness of the EQ-5D and SF-6D differs according to the direction of change. The level of mean change of the EQ-5D relative to the SF-6D has implications for cost-effectiveness analysis. Use of the SF-6D in patients with severe progressive disease may be inappropriate.

Estimating the cost and health status consequences of treatment with TNF antagonists in patients with psoriatic arthritis.

OBJECTIVES: Tumour necrosis factor (TNF) has been shown to improve the outcomes in patients with psoriatic arthritis (PsA). We estimate the long-term impact on health status of prescribing the TNF antagonist etanercept, and evaluate the cost-effectiveness in a health economic model. METHODS: The relationship between disability (Health Assessment Questionnaire) and health state utility was explored to estimate the quality-adjusted life years (QALYs) gained from the TNF antagonist etanercept. A model was then used to compare sequences of treatments for PsA after failure of two conventional disease modifying anti-rheumatic drugs (DMARDs). One arm commences on etanercept therapy and this is compared with a strategy commencing with combination therapy of methotrexate and ciclosporin and another commencing with leflunomide. Individual patient data from Phase III etanercept trials is used to populate the model supported by published evidence from extensive literature searches. By incorporating a life table specific for a PsA population, and using a number of evidence- and expert opinion-based assumptions for disease progression, the model was extended beyond the trial duration to a 10-yr time horizon. Cost offsets were produced by avoiding surgery through delayed progression; drug and monitoring costs were also modelled. RESULTS: Over the 10 yrs, modelled etanercept treatment gave 0.82 more QALYs when compared with combination therapy with methotrexate and ciclosporin, and 0.65 more QALYs in comparison with leflunomide. This equates to a central estimate for the cost per QALY of pound28 189 and pound28 189 for ciclosporin and leflunomide, respectively. Sensitivity analyses demonstrated this could vary by as much as +/-28%. CONCLUSIONS: With limited data currently available, the potential cost-effectiveness of etanercept in DMARD failures for adults with PsA appears encouraging. The result for other TNF antagonists will depend on how their relative efficacy and drug price compares with etanercept. A number of limitations are described and priorities for further research suggested.

Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheumatoid arthritis in Sweden.

BACKGROUND: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions. OBJECTIVE: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board). METHODS: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs. RESULTS: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries. CONCLUSION: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.