C C Earle1, B Pham, G A Wells. 1. University of Ottawa and Ottawa Regional Cancer Centre, Ontario, Canada. craig_earle@dfci.harvard.edu
Abstract
PURPOSE: To assess the accuracies of different techniques for combining published survival curves, for use in disease modeling applications. METHODS: Five methods were identified: 1) iterative generalized least-squares (IGLS), 2) meta-analysis of failure-time data with adjustment for covariates (MFD), 3) nonlinear regression (NLR), 4) log relative risk (LRR), and 5) weighted LRR (w-LRR). Each method was used to combine the survival curves from eight single-arm Phase II trials of chemotherapy in 918 patients with advanced non-small-cell lung cancer (NSCLC). The resulting summary curves were compared with the curve calculated from the corresponding individual patient data (IPD). RESULTS: All methods were able to produce accurate summary survival curves statistically similar to the IPD-derived curve. Maximum discrepancies ranged from 1.8% to 4.7%. MFD appeared to be the most accurate when censoring information was complete. Characteristics of the component trials that adversely affected the accuracies of the different techniques were 1) a high proportion of censored observations (MFD); 2) variability in the length of follow-up (IGLS, NLR, LRR, w-LRR); and 3) the heterogeneity of the treatment results (NLR, w-LRR). CONCLUSIONS: All methods were able to accurately reproduce summary survival curves from the published literature. The best method depends on characteristics of the data and the purpose of the analysis.
PURPOSE: To assess the accuracies of different techniques for combining published survival curves, for use in disease modeling applications. METHODS: Five methods were identified: 1) iterative generalized least-squares (IGLS), 2) meta-analysis of failure-time data with adjustment for covariates (MFD), 3) nonlinear regression (NLR), 4) log relative risk (LRR), and 5) weighted LRR (w-LRR). Each method was used to combine the survival curves from eight single-arm Phase II trials of chemotherapy in 918 patients with advanced non-small-cell lung cancer (NSCLC). The resulting summary curves were compared with the curve calculated from the corresponding individual patient data (IPD). RESULTS: All methods were able to produce accurate summary survival curves statistically similar to the IPD-derived curve. Maximum discrepancies ranged from 1.8% to 4.7%. MFD appeared to be the most accurate when censoring information was complete. Characteristics of the component trials that adversely affected the accuracies of the different techniques were 1) a high proportion of censored observations (MFD); 2) variability in the length of follow-up (IGLS, NLR, LRR, w-LRR); and 3) the heterogeneity of the treatment results (NLR, w-LRR). CONCLUSIONS: All methods were able to accurately reproduce summary survival curves from the published literature. The best method depends on characteristics of the data and the purpose of the analysis.
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