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Improving Mixture Cure Modelling of Molecular Genetic Biomarkers in Cancer Prognosis by Penalized Maximum Likelihood
In analysis of time-to-event data, the mixture cure (MC) model is more appropriate than conventional Cox proportional hazards model when the study sample includes long-term survivors. However, in samples with few events, standard maximum likelihood estimation (MLE) can be biased. We extend Firth-type penalized likelihood estimation (FT-PLE) developed for bias reduction in the exponential family to the Weibull-logistic MC, using the Jeffreys invariant prior. Via simulation studies based on a motivating analysis of multiple protein biomarkers for disease recurrence in breast cancer, we compare FT-PLE vs MLE for effect estimate bias, and type 1 error and power for likelihood ratio statistics(LR), including log-F prior and modified FT-PLE methods. Under a low event-rate model, FT-PLE estimates could always be obtained when MLEs were infinite, and had smallest mean bias among all four methods. We demonstrate good type 1 error control for FT-PLE LR and better power than MLE LR.
Date and Time
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Additional Authors and Speakers (not including you)
Shelley Bull
Lunenfeld-Tanenbaum Research Institute, Sinai Health System; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto
Language of Oral Presentation
English
Language of Visual Aids
English

Speaker

Edit Name Primary Affiliation
Changchang Xu University of Toronto