John A. Carter

Cost-Effectiveness of Denosumab Versus Zoledronic Acid in the Management of Skeletal Metastases Secondary to Breast Cancer

BACKGROUND Denosumab has been approved in the United States for the prevention of skeletal-related events (SREs) in metastatic breast cancer. In a Phase III trial in patients with bone-metastatic breast cancer (N = 2033), denosumab was associated with a significantly delayed time to first SRE (by 18%; P < 0.001 noninferiority; P = 0.01 superiority) and time to first and subsequent SREs (by 23%; P = 0.001). Overall survival (HR = 0.95; 95% CI, 0.81-1.11; P = 0.49) and disease progression (HR = 1.00; 95% CI, 0.89-1.11; P = 0.93) did not differ significantly between groups. Denosumab was associated with a nonsignificant reduction in serious adverse events (44.4% vs 46.5%). OBJECTIVES Given the current ambiguity regarding the cost-effectiveness of these agents in light of these trial outcomes, the present analysis assessed, from a US payer perspective, the cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases secondary to breast cancer. METHODS A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs) gained, number and costs of SREs, and drug and administration costs in patients receiving denosumab or zoledronic acid over 27 and 60 months. Clinical inputs reproduced the trial outcomes. SRE-related costs and utilities were literature based. Costs and QALYs were discounted 3% annually. RESULTS In the 27-month base-case analysis, denosumab was associated with fewer SREs (-0.298), more QALYs (+0.0102), and lower SRE-related costs (-

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

2016), but higher drug-related (+

Estimating Preference-Based EQ-5D Health State Utilities or Item Responses from Neuropathic Pain Scores

9123) and total costs (+

Cost-Effectiveness of Zoledronic Acid in the Management of Skeletal Metastases in Patients With Lung Cancer in France, Germany, Portugal, The Netherlands, and the United Kingdom

7107) versus zoledronic acid. The cost per QALY gained (ie, incremental cost-effectiveness ratio [ICER]) was

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France, Germany, Portugal, and the Netherlands

697,499. In sensitivity analyses, the ICER ranged from

Mapping of the Insomnia Severity Index and other sleep measures to EuroQol EQ-5D health state utilities

192,472 to

Pharmacoeconomics of Bisphosphonates for Skeletal-Related Event Prevention in Metastatic Non-Breast Solid Tumours

1,340,901/QALY, depending on assumptions regarding treatment benefits, drug costs, and analytical horizon. In the probabilistic sensitivity analysis, denosumab was cost-effective in 2 of 5000 modeled replicates (0.04%). CONCLUSIONS Despite the limitations of restricted availability of clinical data and uncertainty regarding the price of generic zoledronic acid, the findings from the present analysis suggest that the use of denosumab is associated with a high ICER compared with zoledronic acid. This finding may raise important questions regarding the economic value of denosumab in bone-metastatic breast cancer.

Qualitative modification and development of patient- and caregiver-reported outcome measures for iron chelation therapy

Abstract Objective: To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients. Methods: Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review. Results: The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p = 0.26 vs etanercept; p = 0.86 vs adalimumab), adalimumab (p = 0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p < 0.001 vs etanercept; p = 0.18 vs adalimumab), 0.63 for adalimumab (p = 0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France). Conclusions: Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.

Modification of Patient Reported Outcomes Measures of Compliance, Gastrointestinal Symptoms, Palatability and Treatment Satisfaction for Patients Needing Iron Chelation therapy

BackgroundPreference-based health state utilities are required for many health economic evaluations. When the direct evidence of such is lacking and only condition-specific scores are available, establishing a ‘mapping’ relationship between instruments can be useful.ObjectiveOur objective was to map the 11-point Pain Intensity Numerical Rating Scale (PI-NRS-11), a pain-specific instrument ranging from 0 (‘no pain’) to 10 (pain as bad as you can imagine’), to the EQ-5D, a preference-based generic instrument.MethodsWe used web survey data collected from adult US respondents who (i) had ≥3 months of neuropathic pain (NP), either painful diabetic peripheral neuropathy (pDPN) or post-herpetic neuralgia (PHN); (ii) were receiving medications treating NP; and (iii) had completed the EQ-5D and PI-NRS-11. We explored indirect and direct mapping approaches. The indirect method took a probabilistic approach using ordered logistic models (OLMs) predicting response levels for each EQ-5D item via repeated Monte Carlo simulations before computing utilities. The direct approach simply predicted EQ-5D utilities directly using ordinary least squares (OLS). Categorical scores of PI-NRS-11 were used as the predictors. Patient age, gender, and pain duration were additionally controlled in the full model specification. Seventy percent of the data were used for estimation and 30% for prediction. Mean square errors (MSEs) and 95% confidence intervals (CIs) of prediction errors were reported. Results: A total of 2719 respondents were included. Mean (SD) age was 55.48 (10.65) years and 56.23% were female. Average NP duration was 61 months and 58% gave scores ≥6 on the PI-NRS-11. The clinical pain scores were significantly associated with all EQ-5D items, especially with the ‘pain/discomfort’ item (p < 0.001). The observed mean (SD) EQ-5D index was 0.594 (0.22). Predicted utilities and responses showed good representation of the observed ones. The reduced model showed comparable results with the full model while imposing minimum data collection burden. From the reduced model, the predicted mean (SD) EQ-5D index was 0.594 (0.11) from direct estimation and 0.588 (0.19) from indirect estimation. All estimated utilities discriminated health gains/losses along the PI-NRS-11. Lower MSEs and prediction errors were found for EQ-5D >0.2.ConclusionsFindings suggest that EQ-5D utilities or item responses could be estimated on the basis of NP scores. Independent testing of the external validity of the mapping algorithms developed herein is encouraged.

PCN66 Cost-Effectiveness of Denosumab Versus Zoledronic Acid for Skeletal-Related Event (SRE) Reduction in Bone-Metastatic Prostate Cancer (mPC) in the UK

BACKGROUND Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients with non-small cell lung cancer (NSCLC) who have bone metastases. OBJECTIVE The purpose of this study was to assess the cost and cost-effectiveness of ZOL in the management of skeletal metastases in this population across 5 European countries (France, Germany, United Kingdom, Portugal, and the Netherlands) from the perspective of national health care. METHODS This cost-effectiveness analysis was based on a subset of patients with NSCLC who were enrolled in a Phase III trial of patients with bone metastases secondary to a variety of solid tumors. In this trial, patients were randomized to receive ZOL or placebo every 3 weeks for up to 21 months. Survival, SRE incidence, and number of infusions administered were derived from the clinical trial. Costs of SREs were estimated using hospital Diagnosis Related Group tariffs and published data. Drug, drug administration, and supply costs were obtained from published and internet sources. Quality-adjusted life-years (QALYs) were estimated based on the published utilities and modeled survival and frequency of SREs. Uncertainty surrounding outcomes was addressed via univariate and probabilistic sensitivity analyses. RESULTS Compared with patients receiving placebo (n = 120), patients receiving ZOL (n = 124) experienced an estimated 0.79 fewer SREs and gained an estimated 0.02 QALYs. ZOL use in patients with NSCLC and bone metastases was associated with a reduction in SRE costs (ranging from €1547 to €1893 [2007-2008 €], depending on the country). After adding drug and drug administration costs, ZOL use resulted in a net savings of €288 per patient in Germany, €209 in the United Kingdom, and €113 in Portugal. In France and the Netherlands, costs increased (€17 and €178, respectively), but the costs per QALY gained were low (€786 and €8278, respectively). In univariate sensitivity analyses, the cost per QALY for ZOL versus placebo was ≤€50,000 for all scenarios tested. The results were most sensitive to assumptions regarding survival, number of ZOL infusions, and the costs of SREs. The probabilistic sensitivity analysis indicated that ZOL cost ≤€50,000 per QALY in 65% to 83% of model simulations (depending on country). However, some degree of uncertainty remained as the 95th percentile of cost per QALY was high. CONCLUSIONS This analysis is subject to the usual limitations of cost-effectiveness models, which combine assumptions and data from multiple sources. Nevertheless, based on the assumptions used herein, the present model suggests that ZOL increases QALYs and is cost saving and/or cost effective compared with placebo in patients with NSCLC in France, Germany, the United Kingdom, Portugal, and the Netherlands.