Bansback NJ, Regier DA, Ara R, Brennan A, Shojania K, Esdaile JM, Anis AH, Marra CA

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies. The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long-term randomised studies where efficacy and resource consumption in comparison with standard care has been investigated. As such, investigators combined short-term randomised control trial data with that of a long-term observational cohort, and modelled cost effectiveness over an appropriate time horizon. In addition, most analyses lacked rigorous sensitivity analysis to examine the impact of uncertainty in the parameters. Those analyses that examined time horizons of 6 months and 1 year published incremental cost-effectiveness ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and 96,166 US dollars (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between 26,800 US dollars (patients’ lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values). In terms of HR-QOL, the analyses reported incremental QALYs that ranged from 0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years, 1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002 values) to 84,000 US dollars (22 years, 1998 values).

Drugs. 2005;65(4):473-96

Espallargues M, Czoski-Murray CJ, Bansback NJ, Carlton J, Lewis GM, Hughes LA, Brand CS, Brazier JE

PURPOSE: To estimate health status utility values in patients with age-related macular degeneration (ARMD) associated with visual impairments, by using preference-based measures of health. METHOD: This was a cross-sectional study involving patients with unilateral or bilateral ARMD who attended a large teaching hospital. Patients underwent visual tests (near and distant visual acuity [VA] and contrast sensitivity [CS]) and completed health status questionnaires including the Index of Visual Function (VF)-14 and three preference-based measures (the Health Utilities Index Mark III [HUI-3], the EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is presented for five groups, defined according to the VA in the better-seeing eye and for four CS groups. RESULTS: Two hundred nine patients were recruited with substantial loss of visual function as obtained by visual tests (mean decimal VA in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean (+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/- 0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a regression model with CS and VA as explanatory variables, only the coefficient on CS was statistically significant. CONCLUSIONS: ARMD is associated with a substantial impact on patients’ health status, but this was not reflected in two of the generic preference-based measures used. The HUI-3 seems to be the instrument of choice for use in economic evaluations in which community data are needed. It may be more appropriate to base economic models on CS or some combination of CS and VA rather than on VA alone.

Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4016-23

Bansback N, Brennan A, Anis AH

The past 10 years has witnessed a major transformation in the treatment of rheumatoid arthritis, a chronic condition that leads to significant morbidity, impairment in quality of life and mortality. Adalimumab joins a class of biologic response modifiers that prevent joint destruction and maintain functional status. For expensive interventions such as biologic response modifiers to be a valuable use of healthcare resources, they must lower healthcare costs by reducing the prevalence of hospitalizations, assist people with rheumatoid arthiritis in maintaining employment and improve patient quality of life. The rheumatoid artiritis market is competitive and growing quickly. Policy makers are faced with decisions surrounding the value of biologic response modifiers over conventional therapies, and whether one biologic response modifier has an advantage over another.

Expert Rev Pharmacoecon Outcomes Res. 2005 Oct;5(5):519-29

Bansback NJ, Brennan A, Ghatnekar O

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.

Ann Rheum Dis. 2005 Jul;64(7):995-1002

Bansback NJ, Brennan A, Ghatnekar O

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.

Ann Rheum Dis. 2005 Jul;64(7):995-1002