Bansback N, Davis S, Brazier J

AIMS: To re-evaluate the cost-effectiveness of photodynamic therapy with verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly classic and classic choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD), using new evidence on the impact of contrast sensitivity on health status. METHOD: A health economic model is used to synthesise the evidence on contrast sensitivity and treatment rates from the TAP Investigation with health state utilities and costs. Impairment of visual function is estimated using a Markov model to predict transitions between states of contrast sensitivity. Each state is associated with costs and a health state utility. Total expected costs and benefits for a cohort of patients over a defined number of cycles are calculated. The expected health state utility for each disease state was estimated using results from a study of 209 patients with AMD in Sheffield. The model includes the costs associated with treatment and monitoring in the verteporfin treatment arm and costs offset by delaying the deterioration of visual function. RESULTS: Beyond 3 years, the annual costs of the verteporfin arm are estimated to be less than the annual costs of the control arm, owing to the cost associated with higher blindness prevalence in the control arm. Over time, the results show that both the incremental utility and cost decreases. By 10 years, the estimated incremental cost-effectiveness is approximately pound20 996 per Quality-Adjusted Life Years. CONCLUSION: The results of this study suggest that the verteporfin therapy in the treatment for patients with predominantly classic and classic CNV owing to AMD is encouraging.

Eye (Lond). 2007 Dec;21(12):1455-63

Bansback N, Marra C, Tsuchiya A, Anis A, Guh D, Hammond T, Brazier J

OBJECTIVE: To estimate the relationship between preference-based measures, EuroQol (EQ-5D) and SF-6D, and the Health Assessment Questionnaire (HAQ) disability index (DI) in patients with rheumatoid arthritis (RA), and to characterize components that are predictors of health utility. METHODS: Patients with RA participating in 2 studies in the UK (n = 151) and Canada (n = 319) completed the HAQ, EQ-5D, and Short Form 36 (SF-36). The SF-36, a generic measure of quality of life, was converted into the preference-based SF-6D. From these results we developed models of the relationship between the HAQ and SF-6D and EQ-5D using various regression analyses. RESULTS: The optimal model developed for the EQ-5D entered levels for each item as independent variables (model 5). A root mean square error (RMSE) of 0.18 suggested relatively good predictive ability. For the SF-6D, RMSEs were lower (0.09), suggesting better predictions than for the EQ-5D, but models with more explanatory variables did not improve results (model 2 or 4 optimal). The models were able to predict actual SF-6D and EQ-5D across the range of the HAQ DI. CONCLUSION: Our approach enabled calculations of quality-adjusted life years from existing trials where only the HAQ was measured. All aspects of the HAQ may not be reflected in the preference-based measures, and this method is suboptimal to direct measurement of health state utility in clinical trials. Given this limitation, our approach provides an alternative for researchers who need health-state utility values, but had not included a preference-based measure in their clinical study because of resource constraints or a desire to limit patient burden.

Arthritis Rheum. 2007 Aug 15;57(6):963-71

Brennan A, Bansback N, Nixon R, Madan J, Harrison M, Watson K, Symmons D

OBJECTIVE: To evaluate the cost effectiveness of TNF-alpha antagonist therapies for rheumatoid arthritis (RA) in the United Kingdom using data from the British Society for Rheumatology Biologics Registry (BSRBR). METHODS: A simulation model is constructed to quantify the cost effectiveness of the TNF-alpha antagonist therapies (infliximab, etanercept and adalimumab) as a group versus traditional disease-modifying anti-rheumatic drugs, with a time horizon over the full patient lifetime. Participants are UK NHS patients in the BSRBR with RA who have failed at least two traditional disease-modifying anti-rheumatic drugs. The BSRBR aims to recruit all RA patients starting on a TNF-alpha antagonist agent and follows them 6 monthly via consultant and patient administered questionnaires. Data collected include disease activity scores (DAS28), the Health Assessment Questionnaire and the SF-36. Costs include drug, monitoring and hospitalisations. Benefits are measured in disability and quality of life improvements. The main outcome measure is the incremental cost per quality adjusted life-year gained (discounted). RESULTS: The basecase cost per quality adjusted life-year gained by using TNF-alpha antagonist therapies is estimated at pound23 882, with probabilistic uncertainty analysis suggesting that the probability that treatments are below 30,000 pounds per QALY is around 84%. The results are most sensitive to assumptions concerning long-term disability progression, discount rates and the validity or otherwise of SF6D derived utility measures. Subgroup analysis, monotherapy versus combination with methotrexate, and a limited analysis of sequential therapy with two TNF-alpha antagonist agents, suggest cost-effectiveness ratios around 20,000 pounds to 30,000 pounds. CONCLUSIONS: The BSRBR data provide valuable evidence for estimating cost-effectiveness. The analysis concludes that current policies and practice for the use of TNF-alpha antagonist therapies, after RA patients have failed at least two traditional disease-modifying anti-rheumatic drugs, appear cost-effective in the context of the NICE re-appraisal of 2006 for England and Wales, thus supporting their decision to continue their reimbursement. Decision-makers worldwide might adapt this analysis because differential costs, discount rates and other factors could affect results. There remains uncertainty, particularly on long-term disease progression. Further data collection using the BSRBR is recommended, together with a revision to this analysis when data become available.

Rheumatology (Oxford). 2007 Aug;46(8):1345-54

Nixon R, Bansback N, Brennan A

OBJECTIVE: New treatments that inhibit the cytokines tumour necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments. METHODS: Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables. RESULTS: In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNFalpha antagonists to be more efficacious compared with anakinra (P < 0.05). Indirect comparisons between the three TNFalpha antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results. CONCLUSION: When the outcome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNFalpha antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNFalpha antagonist class are no different from each other.

Rheumatology (Oxford). 2007 Jul;46(7):1140-7

Bansback N, Maetzel A, Drummond M, Anis A, Marra C, Conway P, Boers M, Tugwell P, Boonen A

Since healthcare resources are scarce, choices have to be made on how they will be allocated. The use of economic evaluations using cost-effectiveness analyses has increased rapidly as policymakers have realized their value in maximizing the population’s benefits (in terms of length of life and health status) within a given budget. Following efforts by OMERACT to create reference case definitions for the conduct of economic evaluation in rheumatoid arthritis, osteoporosis, and osteoarthritis, we review various methodological areas and research decisions that could benefit from a consensus between researchers, clinicians, and drug developers in terms of an ankylosing spondylitis (AS) reference case. Ten methodological issues are presented that will be important for future development of evaluations. Tentative proposals to define the issues in a reference case for AS are made, along with recommendations for further research.

J Rheumatol. 2007 May;34(5):1178-83

Bansback N, Czoski-Murray C, Carlton J, Lewis G, Hughes L, Espallargues M, Brand C, Brazier J

BACKGROUND: There has been increasing interest in the use of measures of health related quality of life (HRQoL) and health state utility values in Age Related Macular Degeneration (ARMD). Visual acuity has been found to be an important determinant of such measures in previous studies. More recently, another measure of visual impairment, contrast sensitivity has received considerable attention. We designed a study to examine whether the contribution of contrast sensitivity in explaining HRQoL and health utilities over and above that of visual acuity. METHODS: 209 patients with unilateral or bilateral ARMD were recruited into a cross-sectional study of patients from a large teaching hospital. Patients underwent visual tests (near and distant visual acuity, contrast sensitivity) and completed a vision function questionnaire, the VF-14, HUI3, and time trade-off. RESULTS: Using multivariate regression analysis, the study revealed that contrast sensitivity remained a statistically significant predictor of all outcome measures even when visual acuity was included. This result was supported by the correlation coefficients between measures. CONCLUSIONS: The measurement of contrast sensitivity appears to be better related to a person’s HRQoL and health utility. Future studies should consider incorporating contrast sensitivity in addition to visual acuity. Studies, in particular economic evaluations, may underestimate the effect of treatment unless contrast sensitivity is considered.

Qual Life Res. 2007 Apr;16(3):533-43

Nixon RM, Bansback N, Brennan A

Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of the same treatment for a disease being tested in a number of studies, a number of different interventions are considered. Meta-regression is also a generalization of meta-analysis where an attempt is made to explain the heterogeneity between the treatment effects in the studies by regressing on study-level covariables. Our focus is where there are several different treatments considered in a number of randomized controlled trials in a specific disease, the same treatment can be applied in several arms within a study, and where differences in efficacy can be explained by differences in the study settings. We develop methods for simultaneously comparing several treatments and adjusting for study-level covariables by combining ideas from MTC and meta-regression. We use a case study from rheumatoid arthritis. We identified relevant trials of biologic verses standard therapy or placebo and extracted the doses, comparators and patient baseline characteristics. Efficacy is measured using the log odds ratio of achieving six-month ACR50 responder status. A random-effects meta-regression model is fitted which adjusts the log odds ratio for study-level prognostic factors. A different random-effect distribution on the log odds ratios is allowed for each different treatment. The odds ratio is found as a function of the prognostic factors for each treatment. The apparent differences in the randomized trials between tumour necrosis factor alpha (TNF- alpha) antagonists are explained by differences in prognostic factors and the analysis suggests that these drugs as a class are not different from each other. Copyright (c) 2006 John Wiley & Sons, Ltd.

Stat Med. 2007 Mar 15;26(6):1237-54