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Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials

Abstract : Background: Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions. Methods: Based on a parsimonious biomarker selection in a penalized high-dimensional Cox model (lasso or adaptive lasso), we propose a unified framework to: estimate internally the predictive accuracy metrics of the developed model (using double cross-validation); estimate the individual survival probabilities at a given timepoint; construct confidence intervals thereof (analytical or bootstrap); and visualize them graphically (pointwise or smoothed with spline). We compared these strategies through a simulation study covering scenarios with or without biomarker effects. We applied the strategies to a large randomized phase III clinical trial that evaluated the effect of adding trastuzumab to chemotherapy in 1574 early breast cancer patients, for which the expression of 462 genes was measured.
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https://www.hal.inserm.fr/inserm-01529738
Contributor : Stefan Michiels <>
Submitted on : Wednesday, May 31, 2017 - 12:29:20 PM
Last modification on : Wednesday, September 16, 2020 - 5:26:21 PM

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Nils Ternès, Federico Rotolo, Stefan Michiels. Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials. BMC Medical Research Methodology, BioMed Central, 2017, 17 (1), pp.83. ⟨10.1186/s12874-017-0354-0⟩. ⟨inserm-01529738⟩

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