The Predicted Impact of Ipilimumab Usage on Survival in Previously Treated Advanced or Metastatic Melanoma in the UK.

BACKGROUND: Evaluating long-term prognosis is important for physicians, patients and payers. This study reports the results of a model developed to predict long-term survival for UK patients receiving second-line ipilimumab. METHODS: MDX010-20 trial data were used to predict survival for ipilimumab versus UK best supportive care. Two aspects of this analysis required novel approaches: 1) The overall survival Kaplan-Meier data shape is unusual: an initial steep decline is observed before a 'plateau'. 2) The need to extrapolate beyond the trial end (4.6 years). Based upon UK clinician advice, a three-part curve fit was used: from 0-1.5 years, Kaplan-Meier data from the trial; from 1.5-5 years, standard parametric curve fits; after 5 years, long-term data from the American Joint Committee on Cancer registry. RESULTS: This approach provided good internal validity: low mean absolute error and good match to median and mean trial data. Lifetime predicted means were 2.77 years for ipilimumab and 1.07 for best supportive care, driven by increased long-term survival with ipilimumab. CONCLUSION: To understand the full benefit of treatment and to meet reimbursement requirements, accurate estimation of treatment benefit is key. Models, such as the one presented, can be used to extrapolate beyond trials.

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

BACKGROUND: Health-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. METHODS: Utilities 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. RESULTS: Mean 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. CONCLUSIONS: Patient-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.

Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom.

OBJECTIVE: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom. METHODS: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL). RESULTS: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months. CONCLUSION: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.

Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis.

INTRODUCTION: The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR). METHODS: A systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI). RESULTS: The analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Abatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.

Cost effectiveness of palivizumab in children with congenital heart disease in Germany.

OBJECTIVES: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting. STUDY DESIGN: A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis). RESULTS: From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting. CONCLUSION: This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.

Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands.

BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences. OBJECTIVE: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting. METHODS: A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands. RESULTS: The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting. CONCLUSION: Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.

Costs of medication nonadherence in patients with diabetes mellitus: a systematic review and critical analysis of the literature.

OBJECTIVES: Information on the health care costs associated with nonadherence to treatments for diabetes is both limited and inconsistent. We reviewed and critically appraised the literature to identify the main methodological issues that might explain differences among reports in the relationship of nonadherence and costs in patients with diabetes. METHODS: Two investigators reviewed Medline, EMBASE, Cochrane library and CINAHL and studies with information on costs by level of adherence in patients with diabetes published between January 1, 1997 and September 30th 2007 were included. RESULTS: A total of 209 studies were identified and ten fulfilled the inclusion criteria. All included studies analyzed claims data and 70% were based on non-Medicaid and non-Medicare databases. Low medication possession ratios were associated with higher costs. Important differences were found in the ICD-9/ICD-9 CM codes used to identify patients and their diagnoses, data sources, analytic window period, definitions of adherence measures, skewness in cost data and associated statistical issues, adjustment of costs for inflation, adjustment for confounders, clinical outcomes and costs. CONCLUSIONS: Important variation among cost estimates was evident, even within studies of the same population. Readers should be cautious when comparing estimated coefficients from various studies because methodological issues might explain differences in the results of costs of nonadherence in diabetes. This is particularly important when estimates are used as inputs to pharmacoeconomic models.

Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria. METHODS: A decision tree model was developed to determine cost-effectiveness in infants born prematurely (

Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.

OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD). METHODS: A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.