Cost-Effectiveness and Value of Information of Erlotinib, Afatinib, and Cisplatin-Pemetrexed for First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer in the United States.

OBJECTIVES: To determine the cost-effectiveness of tyrosine kinase inhibitors erlotinib or afatinib, or chemotherapy cisplatin-pemetrexed, for first-line treatment of advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer in the United States. We also assessed the expected benefit of further research to reduce uncertainty regarding which treatment is optimal. METHODS: We developed a Markov model to compare the cost-effectiveness of erlotinib, afatinib, and cisplatin-pemetrexed. Model transition and adverse-effect probabilities were from two published phase III trials: EURTAC (Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) and LUX-Lung (Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma) 3. EURTAC survival estimates were corrected for patients entering the trial with more severe disease, compared with LUX-Lung 3. Health utilities and costs were from national estimates or the published literature. Inputs were modeled as distributions for probabilistic sensitivity analysis and expected value of perfect information (EVPI) analysis to estimate the expected benefit of reducing uncertainty regarding the decision of optimal treatment. RESULTS: In the base case, both tyrosine kinase inhibitors were more cost-effective than cisplatin-pemetrexed. Erlotinib had an incremental cost-effectiveness ratio of $61,809/quality-adjusted life-year (QALY) compared with afatinib. The acceptability curve showed that erlotinib was the optimal treatment at a willingness-to-pay threshold of $100,000/QALY (10-year population EVPI = $85.9 million). At a willingness-to-pay threshold of $50,000/QALY to $70,000/QALY (EVPI = $211.5 million-$261.8 million), however, there was considerable uncertainty whether erlotinib or afatinib was the optimal treatment. CONCLUSIONS: Our analysis suggests that erlotinib is the preferred first-line treatment for advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer. Further research comparing erlotinib and afatinib is potentially justified, although accurate data are needed on the required cost and sample size of the trial.

The Food and Drug Administration reports provided more data but were more difficult to use than the European Medicines Agency reports.

OBJECTIVES: To compare the accessibility, comprehensiveness, and usefulness of data available from the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) drug reports. STUDY DESIGN AND SETTING: This is a cross-sectional study. All new molecular drugs approved between January 1, 2011 and December 31, 2012 from the FDA and EMA Web sites were eligible. RESULTS: We included 27 drug reports. Most were searchable, but the FDA table of contents did not match the file's page numbers. Several FDA documents must be searched compared with a single EMA document, but the FDA reports contain more summary data on harms. Detailed information about harms was reported for 93% of the FDA reports (25 of 27 reports) and 26% of the EMA reports (7 of 27 reports). The reports contained information about trial methodology but did not include trial registry IDs or investigator names. All reports but one contained sufficient information to be used in a meta-analysis. CONCLUSION: Detailed data on efficacy and harms are available at the two agencies. The FDA has more summary data on harms, but the documents are harder to navigate.

The Relationship between Risk of Bias Criteria, Research Outcomes, and Study Sponsorship in a Cohort of Preclinical Thiazolidinedione Animal Studies: A Meta-Analysis.

INTRODUCTION: There is little evidence regarding the influence of conflicts of interest on preclinical research. This study examines whether industry sponsorship is associated with increased risks of bias and/or effect sizes of outcomes in published preclinical thiazolidinedione (TZD) studies. METHODS: We identified preclinical TZD studies published between January 1, 1965 and November 14, 2012. Coders independently extracted information on study design criteria aimed at reducing bias, results for all relevant outcomes, sponsorship source, and investigator financial ties from the 112 studies meeting the inclusion criteria. The average standardized mean difference (SMD) across studies was calculated for plasma glucose (efficacy outcome) and weight gain (harm outcome). In subgroup analyses, TZD outcomes were assessed by sponsorship source and risk of bias criteria. RESULTS: Seven studies were funded by industry alone, 17 studies funded by both industry and non-industry, 49 studies funded by non-industry alone, and 39 studies had no disclosures. None of the studies used sample size calculations, intention-to-treat analyses, blinding of investigators, or concealment of allocation. Most studies reported favorable results (88 of 112) and conclusions (95 of 112) supporting TZD use. Efficacy estimates were significantly larger in 6 studies sponsored by industry alone (-3.41; 95% CI -5.21, -1.53; I2 = 93%) versus 42 studies sponsored by non-industry sources (-0.97; 95% CI -1.37, -0.56; I2 = 81%) (p value = 0.01). Harms estimates were significantly larger in 4 studies sponsored by industry alone (5.00; 95% CI 1.22, 8.77; I2 = 93%) versus 38 studies sponsored by non-industry sources (0.30; 95% CI -0.08, 0.68; I2 = 79%) (p value = 0.02). TZD efficacy and harms did not differ by disclosure of financial COIs or risks of bias. CONCLUSIONS: Industry-sponsored TZD animal studies have exaggerated efficacy and harms outcomes compared to studies funded by non-industry sources. There was poor reporting of COIs.