Becky Pennington

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK

Abstract Background: Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK. Methods: A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n = 1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective. Results: At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000–£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY. Conclusion: OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.

Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death

BackgroundHealth-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death.MethodsUtilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared.ResultsMean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature.ConclusionsPatient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas.

Mapping from the Health Assessment Questionnaire to the EQ-5D: The Impact of Different Algorithms on Cost-Effectiveness Results

BACKGROUND Many algorithms exist for converting the Health Assessment Questionnaire (HAQ) score to utility in rheumatoid arthritis (RA). Different algorithms convert the same HAQ score to different utility values, and could therefore lead to different cost-effectiveness results. OBJECTIVE To investigate the impact of different mapping algorithms within the same cost-effectiveness model. METHODS We rebuilt an existing economic model that had previously been used for estimating the cost-effectiveness of second-line biologics in RA. We reviewed the literature to identify algorithms that converted the HAQ score to utility and incorporated them into the model. We compared the cost-effectiveness results using different algorithms, exploring the reasons behind the different results and the potential effect on reimbursement decisions. RESULTS We identified 24 different algorithms that estimated utility on the basis of the HAQ score, age, sex, and pain. The incremental cost-effectiveness ratio for rituximab versus disease-modifying antirheumatic drugs varied between £18,407/quality-adjusted life-year and £32,039/quality-adjusted life-year, which we speculate could have changed the recommendations made by the National Institute for Health and Care Excellence. CONCLUSIONS Using different algorithms to convert the HAQ score to utility affects the cost-effectiveness of second-line biologics for the treatment of RA. Using different algorithms in economic modeling for RA could lead health technology assessment bodies to make different reimbursement decisions.

A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

Abstract Objectives: Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket–Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. Methods: The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. Results: Over a patient’s lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313kr (

Cost-effectiveness of selective internal radiation therapy using yttrium-90 resin microspheres in treating patients with inoperable colorectal liver metastases in the UK

12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. Conclusions: The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

Smoking Cessation: A Comparison of Two Model Structures

Abstract Objective: Selective internal radiation therapy (SIRT) using SIR-Spheres® 90Y-labeled resin microspheres has been shown to be a well-tolerated, effective treatment in patients with inoperable liver-dominant chemotherapy–refractory metastatic colorectal cancer (mCRC). This study estimated the cost-effectiveness of 90Y-resin microspheres compared to best supportive care (BSC) from a UK perspective. Methods: Survival data from a comparative retrospective cohort study was analyzed and used in a state-transition cost-effectiveness model, using quality-adjusted life years (QALYs) gained as the measure of effectiveness. The model incorporated costs for the SIRT procedure, monitoring, further treatment, adverse events, and death. Utility values, reflecting patient quality-of-life, were taken from a published source. Results: SIRT using 90Y-resin microspheres compared to BSC improved overall survival by a mean of 1.12 life years and resulted in a cost per QALY gained of £28,216. In sensitivity analysis, this varied between £25,015–£28,817. Conclusion: In an area of large unmet need, treatment with 90Y-resin microspheres offers a clinically effective and cost-effective treatment option.

The Impact of Moving from EQ-5D-3L to -5L in NICE Technology Appraisals

BackgroundMost economic evaluations of smoking cessation interventions have used cohort state-transition models. Discrete event simulations (DESs) have been proposed as a superior approach.ObjectiveWe developed a state-transition model and a DES using the discretely integrated condition event (DICE) framework and compared the cost-effectiveness results. We performed scenario analysis using the DES to explore the impact of alternative assumptions.MethodsThe models estimated the costs and quality-adjusted life years (QALYs) for the intervention and comparator from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. The models considered five comorbidities: chronic obstructive pulmonary disease, myocardial infarction, coronary heart disease, stroke and lung cancer. The state-transition model used prevalence data, and the DES used incidence. The costs and utility inputs were the same between two models and consistent with those used in previous analyses for the National Institute for Health and Care Excellence.ResultsIn the state-transition model, the intervention produced an additional 0.16 QALYs at a cost of £540, leading to an incremental cost-effectiveness ratio (ICER) of £3438. The comparable DES scenario produced an ICER of £5577. The ICER for the DES increased to £18,354 when long-term relapse was included.ConclusionsThe model structures themselves did not influence smoking cessation cost-effectiveness results, but long-term assumptions did. When there is variation in long-term predictions between interventions, economic models need a structure that can reflect this.

The cost-effectiveness of seven behavioural interventions to prevent drug misuse in vulnerable populations

BackgroundThe EuroQol-5 Dimension (EQ-5D) instrument is the National Institute for Health and Care Excellence (NICE)’s preferred measure of health-related quality of life (QoL) in adults. The three-level (3L) value set is currently recommended for use, but the five-level (5L) set is increasingly being used in practice.ObjectiveWe aimed to explore the impact of moving from 3L to 5L in NICE appraisals.MethodsWe adapted our existing mapping for use with health state utility values derived from a population where the original distribution of utilities was unknown. We used this mapping to estimate 5L utilities for 21 comparisons of interventions from models used in NICE technology appraisal decision making, covering a range of disease areas.ResultsAll utilities increased using 5L, and the differences between highest and lowest utilities decreased. In ten oncology comparisons, using 5L generally increased the incremental quality-adjusted life-years (QALYs) as the benefit from improving survival increased. In four non-oncology comparisons where the intervention improved QoL only, the incremental QALYs decreased as the benefit of improving QoL was reduced. In seven non-oncology comparisons where interventions improved survival and QoL, there was a trade-off between increasing the benefit from survival and decreasing the benefit from improving QoL.Conclusion3L and 5L lead to substantially different estimates of incremental QALYs and cost effectiveness. The direction and magnitude of the change is not consistent across case studies. Using 5L instead of 3L may lead to different reimbursement decisions. NICE will face inconsistencies in decision making if it uses 3L and 5L concurrently.

OP11 Structural Uncertainty In Economic Modelling For Smoking Cessation

BACKGROUND The National Institute for Health and Care Excellence (NICE) developed a guideline on drug misuse prevention in vulnerable populations. Part of the guideline development process involved evaluating cost-effectiveness and determining which interventions represented good value for money. METHODS Economic models were developed for seven interventions which aimed to prevent drug use in vulnerable populations. The models compared the costs (to the health and crime sectors) and health benefits (in quality-adjusted life years (QALYs)) of each intervention and its comparator. Sensitivity analysis explored the uncertainty associated with the cost of each intervention and duration of its effect. RESULTS The reduction in drug use for each intervention partly offset the costs of the intervention, and improved health outcomes (QALYs). However, with high intervention costs and low QALY gains, none of the interventions were estimated to be cost-effective in the base case. Sensitivity analysis found that some of the interventions could be cost-effective if they could be delivered at a lower cost, or if the effect could be sustained for more than two years. CONCLUSIONS For drug misuse prevention to be prioritised by funders, the consequences of drug misuse need to be understood, and interventions need to be shown to be effective and cost-effective. Quantifying the wider harms of drug misuse and wider benefits of prevention interventions poses challenges in evaluating the cost-effectiveness of drug misuse prevention interventions. A greater understanding of the consequences of drug misuse and causal factors could facilitate development of cost-effective interventions to prevent drug misuse.

Which Metric To Choose For Indirect Comparison Of Treatments When Multiple Comparisons Are Feasible: Lubiprostone Verse Prucalopride In Chronic Constipation

The largest categories of apportioned spend were Cancer (accounting for 12.1 percent of portfolio), and Mental Health (11.8 percent of portfolio) which particularly reflected the 9.8 percent burden of disease to the UK. Most notable deviations from DALY, where spend was lower than disease burden, were in the Cancer, Cardiovascular and Musculoskeletal categories; which may reflect the importance of other, notably charity, funding.