Bansback N, Sun H, Guh DP, Li X, Nosyk B, Griffin S, Barnett PG, Anis AH; OPTIMA TEAM.

The impact of healthcare interventions on health utility values is most frequently measured using a preference-based instrument. Each of the available instruments instructs the respondent to report their health status over different recall periods ranging from the current day to the past month. In an ongoing randomised controlled trial in patients with advanced HIV disease, the impact of using a preference-based instrument with a 1-week recall period vs a 1-day recall period (e.g. today) for capturing recently resolved serious adverse events was measured. The results suggest that the instrument with a 1-week recall period gave lower utility values for recently resolved events in comparison with the instrument with a 1-day recall period. A plausible interpretation of these results is that the recall period was adhered to; for example, patients ignored the impact of recently resolved events in their response if the questionnaire asked them only about their health today. While there are limitations to our study, we believe further consideration should be given to the recall period used for preference-based instruments, and future research should examine other patient groups using a single instrument with multiple recall periods.

Health Econ. 2008 Dec;17(12):1413-9

Bansback N, Sun H, Guh DP, Li X, Nosyk B, Griffin S, Barnett PG, Anis AH; OPTIMA TEAM

The impact of healthcare interventions on health utility values is most frequently measured using a preference-based instrument. Each of the available instruments instructs the respondent to report their health status over different recall periods ranging from the current day to the past month. In an ongoing randomised controlled trial in patients with advanced HIV disease, the impact of using a preference-based instrument with a 1-week recall period vs a 1-day recall period (e.g. today) for capturing recently resolved serious adverse events was measured. The results suggest that the instrument with a 1-week recall period gave lower utility values for recently resolved events in comparison with the instrument with a 1-day recall period. A plausible interpretation of these results is that the recall period was adhered to; for example, patients ignored the impact of recently resolved events in their response if the questionnaire asked them only about their health today. While there are limitations to our study, we believe further consideration should be given to the recall period used for preference-based instruments, and future research should examine other patient groups using a single instrument with multiple recall periods.

Health Econ. 2008 Dec;17(12):1413-9

Bansback N, Ara R, Karnon J, Anis A

We reviewed the clinical measures used in rheumatoid arthritis (RA) economic evaluations with respect to their relevance and sensitivity to changes in survival, health-related quality of life (HR-QOL) and costs. We compared the measures from the economic perspective and discussed the validity of methods used to extrapolate beyond the trial data. Cost-effectiveness evaluations of disease-modifying antirheumatic drugs in RA were identified by searching MEDLINE, EMBASE, Econlit and NHS EED databases. Studies were retained if they extrapolated beyond randomized controlled trial evidence using relationships between clinical measures, costs and utilities. In the 22 studies identified, clinical severity was measured using the Health Assessment Questionnaire (HAQ) Disability Index, the American College of Rheumatology (ACR) response criteria, the Disease Activity Score (DAS) or a combination of the HAQ and DAS. The HAQ is correlated with mortality, costs and HR-QOL instruments, and several studies used linear relationships to model these associations. However, a polynomial relationship or discrete states may be more appropriate for patients at the extremes of the disease spectrum, and numerous HAQ health states may be required to capture differences in mortality risk. While the ACR response criteria is a more comprehensive measure than the HAQ, it is a relative measure, which creates difficulties when estimating absolute changes in HR-QOL, costs and mortality risk. The evidence base linking DAS scores with HR-QOL instruments, costs and mortality is less robust, possibly due to the comparatively recent development of the measure and the limited number of possible scores (mild/moderate/severe). While there is some evidence of a relationship between DAS scores and costs, the DAS does not capture all aspects of HR-QOL, and no significant relationship has been established with mortality risk. Evidence suggests the HAQ to be the primary clinical measure for use in economic evaluations as it is measured in almost all clinical studies, and is closely correlated to health utilities, mortality and costs. While new developments suggest the sensitivity of health states may be improved by combining the HAQ with measures such as the DAS, further research is required in this area. Further research is also required to explore the advantages in using either continuous or discrete health states.

Pharmacoeconomics. 2008;26(5):395-408

Zhang W, Bansback N, Guh D, Li X, Nosyk B, Marra CA, Anis AH

OBJECTIVE: To evaluate the shortterm effect of adalimumab on work productivity in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: In a substudy of the Canadian Adalimumab Clinical Trial (CanAct), clinical, health status, and productivity outcomes were measured at baseline and 12 weeks. Patients were classified as responders and nonresponders by the 20% American College of Rheumatology (ACR20) improvement criterion and the minimum clinically important difference (MCID) of the Health Assessment Questionnaire (HAQ) score (0.22), respectively. The Health and Labour Questionnaire (HLQ) was used to measure productivity outcomes and costs. RESULTS: Included in the analysis were 389 patients completing both baseline and 12-week HLQ questionnaire. Absenteeism (a decrease of 0.5 workdays per 2 weeks) and unpaid work productivity (3.5 fewer hours unpaid help per 2 weeks) were improved significantly after 12 weeks. Improvements in productivity outcomes were associated with clinical response. Bootstrapping results suggest that responders achieved statistically significant improvement in presenteeism (ACR20) and unpaid work productivity (ACR20 and HAQ) versus nonresponders. The costs saved by responders were up to $155.04 per 2 weeks more than those by nonresponders. CONCLUSION: The costs of adalimumab were partially offset, even in the short term, by cost savings induced by clinical response among Canadian patients with moderate to severe RA. These findings complement results of other study analyses that demonstrate early and sustained benefits of adalimumab.

J Rheumatol. 2008 Sep;35(9):1729-36

Bansback N, Harrison M, Brazier J, Davies L, Kopec J, Marra C, Symmons D, Anis A.

Arthritis Rheum. 2008 Jul 15;59(7):1018-26

Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, Bansback N, Beverley C, Bird A, Harding S, Chisholm I, Yang YC.

OBJECTIVES: To estimate the cost-effectiveness of screening for age-related macular degeneration (AMD) by developing a decision analytic model that incorporated and assessed all of the National Screening Committee criteria. A further objective was to identify the major areas of uncertainty in the model, and so inform future research priorities in this disease area. DATA SOURCES: Major databases were searched in March 2004 and updated in January 2005. REVIEW METHODS: Systematic literature reviews covered the epidemiology and natural history of AMD, the screening and treatment effectiveness and health-related quality of life relating to AMD. A hybrid cohort-individual sampling model was implemented to describe the range of pathways between the incidence of age-related maculopathy (ARM) and death via clinical presentation and treatment at different stages of the disease. As significant shortfalls in the data available from the literature were apparent, so a range of primary data sources were also used to populate the model. To obtain estimates for the value of parameters deemed to be within an expert’s remit, data describing some parameters were elicited from relevant experts. The data identified informed probability distributions describing the uncertainty around the model parameters. To incorporate joint parameter uncertainty (i.e. correlations between parameters), the AMD natural history model was calibrated probabilistically. Randomly sampled sets of input parameters were assigned weights representing the accuracy of their predictions of a set of observed model outputs. The analysis of the AMD screening model estimated the costs, numbers of quality-adjusted life-years (QALYs) and cases of blindness in a general population sample of 50-year-olds over the remainder of their lifetime, for 16 alternative screening options (including no screening). The reference case analysis incorporated current treatment options of laser photocoagulation and photodynamic therapy. Sensitivity analyses describing six alternative sets of intervention strategies, based on horizon scanning of potential future treatments for AMD, were also undertaken. RESULTS: There remains significant uncertainty about whether any form of screening for AMD is cost-effective. However, annual screening from age 60 years seems to provide the highest mean net benefits, but this is based on a cost-effectiveness estimate that has very poor precision (high levels of uncertainty). The probabilistic sensitivity analysis shows that the 95% credible interval for annual screening from age 60 years ranges from this option dominating the previous option to an incremental cost per QALY of over 0.5 million pounds sterling. Plotting a cost-effectiveness acceptability frontier shows that although annual screening from age 60 years has the highest net benefits at a value of QALY of 30,000 pounds sterling, the associated probability of this option being the most cost-effective option is only around 20%. The sensitivity analyses around potential future treatment options indicate that screening may become more cost-effective with the new treatments. CONCLUSIONS: The conclusions focus on the interpretation of the results from the perspective of defining the major areas of uncertainty, which were defined as disease progression, rates of clinical presentation, screening test and optician effectiveness, treatment effectiveness, and costs of blindness. Future research may be best targeted at assessing how routine data may be used to describe clinical presentation rates of ARM. Other potential studies include a pilot study of the effectiveness of screening and opticians’ referral patterns for AMD and a costing study of blindness as a continuum of association with deterioration in vision.

Health Technol Assess. 2008 Jun;12(27):iii-iv, ix-124

Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, Bansback N, Beverley C, Bird A, Harding S, Chisholm I, Yang YC

OBJECTIVES: To estimate the cost-effectiveness of screening for age-related macular degeneration (AMD) by developing a decision analytic model that incorporated and assessed all of the National Screening Committee criteria. A further objective was to identify the major areas of uncertainty in the model, and so inform future research priorities in this disease area. DATA SOURCES: Major databases were searched in March 2004 and updated in January 2005. REVIEW METHODS: Systematic literature reviews covered the epidemiology and natural history of AMD, the screening and treatment effectiveness and health-related quality of life relating to AMD. A hybrid cohort-individual sampling model was implemented to describe the range of pathways between the incidence of age-related maculopathy (ARM) and death via clinical presentation and treatment at different stages of the disease. As significant shortfalls in the data available from the literature were apparent, so a range of primary data sources were also used to populate the model. To obtain estimates for the value of parameters deemed to be within an expert’s remit, data describing some parameters were elicited from relevant experts. The data identified informed probability distributions describing the uncertainty around the model parameters. To incorporate joint parameter uncertainty (i.e. correlations between parameters), the AMD natural history model was calibrated probabilistically. Randomly sampled sets of input parameters were assigned weights representing the accuracy of their predictions of a set of observed model outputs. The analysis of the AMD screening model estimated the costs, numbers of quality-adjusted life-years (QALYs) and cases of blindness in a general population sample of 50-year-olds over the remainder of their lifetime, for 16 alternative screening options (including no screening). The reference case analysis incorporated current treatment options of laser photocoagulation and photodynamic therapy. Sensitivity analyses describing six alternative sets of intervention strategies, based on horizon scanning of potential future treatments for AMD, were also undertaken. RESULTS: There remains significant uncertainty about whether any form of screening for AMD is cost-effective. However, annual screening from age 60 years seems to provide the highest mean net benefits, but this is based on a cost-effectiveness estimate that has very poor precision (high levels of uncertainty). The probabilistic sensitivity analysis shows that the 95% credible interval for annual screening from age 60 years ranges from this option dominating the previous option to an incremental cost per QALY of over 0.5 million pounds sterling. Plotting a cost-effectiveness acceptability frontier shows that although annual screening from age 60 years has the highest net benefits at a value of QALY of 30,000 pounds sterling, the associated probability of this option being the most cost-effective option is only around 20%. The sensitivity analyses around potential future treatment options indicate that screening may become more cost-effective with the new treatments. CONCLUSIONS: The conclusions focus on the interpretation of the results from the perspective of defining the major areas of uncertainty, which were defined as disease progression, rates of clinical presentation, screening test and optician effectiveness, treatment effectiveness, and costs of blindness. Future research may be best targeted at assessing how routine data may be used to describe clinical presentation rates of ARM. Other potential studies include a pilot study of the effectiveness of screening and opticians’ referral patterns for AMD and a costing study of blindness as a continuum of association with deterioration in vision.

Health Technol Assess. 2008 Jun;12(27):iii-iv, ix-124

Wailoo AJ, Bansback N, Brennan A, Michaud K, Nixon RM, Wolfe F

OBJECTIVE: Since the introduction of the Medicare Prescription Drug Improvement and Modernization Act and its associated demonstration project, coverage of selected biologic drugs has been expanded for Medicare beneficiaries. For rheumatoid arthritis, coverage was extended to etanercept, adalimumab, and anakinra in addition to the previously covered infliximab. We undertook to develop a model to compare the costs and quality-adjusted life years (QALYs) generated by each of the 4 biologic agents. METHODS: Data were drawn from meta-analysis of randomized controlled trials and from a large longitudinal outcomes databank. Uncertainty was addressed using probabilistic and one-way sensitivity analyses. A lifetime horizon and Medicare viewpoint were adopted. RESULTS: In the base case analysis, anakinra was the least effective and least costly strategy. Etanercept, adalimumab, and infliximab were similar in terms of effectiveness, but infliximab was more costly. If decision makers are willing to pay a maximum of $50,000/QALY, the probability that infliximab is cost-effective is <1%. Findings were robust to a range of sensitivity analyses. Only if the dose of infliximab remains constant over time is this likely to be a cost-effective strategy. CONCLUSION: Infliximab is unlikely to be cost-effective in the Medicare population compared with either etanercept or adalimumab. Anakinra is substantially less costly but is also less effective than the 3 tumor necrosis factor alpha inhibitors.

Arthritis Rheum. 2008 Apr;58(4):939-46

Harrison MJ, Davies LM, Bansback NJ, Ingram M, Anis AH, Symmons DP

OBJECTIVE: Cost-utility analysis is increasingly important as healthcare providers aim to invest scarce resources in interventions offering the greatest health benefit. The ability to attach utility values to health states is essential, and is increasingly performed using generic scales. However, the evidence regarding the validity of generic utility scales in rheumatoid arthritis (RA) is unclear. We summarize and review evidence on the validity and comparative performance of generic utility scales in RA. METHODS: We searched the English-language medical literature for studies using utilities in RA between 1980 and mid-2006. Reports describing primary evidence of the validity or performance of a generic utility scale in RA were selected, summarized, and reviewed using the OMERACT filter. RESULTS: In total 923 articles were identified, of which 228 reported the use of utility scales in RA; 26 studies related to the validation or evidence of generic utility scales in RA, the EQ-5D, Health Utility Index-2 (HUI2) and HUI3, SF-6D, and Quality of Well-Being Scale. The EQ-5D, HUI2 and HUI3, and SF-6D all have consistent evidence of construct validity and responsiveness in RA, but each has limitations. CONCLUSION:The EQ-5D and HUI3 have been the most extensively studied instruments and show validity and responsiveness for use in RA, but both instruments have limitations. The SF-6D is relatively new and appears to have potential for use in milder RA, but needs further evaluation. More longitudinal head-to-head evaluation of measures is needed across the spectrum of RA disease severity to further investigate their comparative properties, and to seek consensus on the best utility measure for use in economic evaluation.

J Rheumatol. 2008 Apr;35(4):592-602

Wailoo A, Bansback N, Chilcott J

Rheumatology (Oxford). 2008 Feb;47(2):119-20