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The C-index Multiverse

Sierra, Begoña B., McLean, Colin, Hall, Peter S., Vallejos, Catalina A.

arXiv.org Machine Learning

Quantifying out-of-sample discrimination performance for time-to-event outcomes is a fundamental step for model evaluation and selection in the context of predictive modelling. The concordance index, or C-index, is a widely used metric for this purpose, particularly with the growing development of machine learning methods. Beyond differences between proposed C-index estimators (e.g. Harrell's, Uno's and Antolini's), we demonstrate the existence of a C-index multiverse among available R and python software, where seemingly equal implementations can yield different results. This can undermine reproducibility and complicate fair comparisons across models and studies. Key variation sources include tie handling and adjustment to censoring. Additionally, the absence of a standardised approach to summarise risk from survival distributions, result in another source of variation dependent on input types. We demonstrate the consequences of the C-index multiverse when quantifying predictive performance for several survival models (from Cox proportional hazards to recent deep learning approaches) on publicly available breast cancer data, and semi-synthetic examples. Our work emphasises the need for better reporting to improve transparency and reproducibility. This article aims to be a useful guideline, helping analysts when navigating the multiverse, providing unified documentation and highlighting potential pitfalls of existing software. All code is publicly available at: www.github.com/BBolosSierra/CindexMultiverse.


Estimating heterogeneous treatment effect from survival outcomes via (orthogonal) censoring unbiased learning

Xu, Shenbo, Cobzaru, Raluca, Zheng, Bang, Finkelstein, Stan N., Welsch, Roy E., Ng, Kenney, Tzoulaki, Ioanna, Shahn, Zach

arXiv.org Machine Learning

Methods for estimating heterogeneous treatment effects (HTE) from observational data have largely focused on continuous or binary outcomes, with less attention paid to survival outcomes and almost none to settings with competing risks. In this work, we develop censoring unbiased transformations (CUTs) for survival outcomes both with and without competing risks.After converting time-to-event outcomes using these CUTs, direct application of HTE learners for continuous outcomes yields consistent estimates of heterogeneous cumulative incidence effects, total effects, and separable direct effects. Our CUTs enable application of a much larger set of state of the art HTE learners for censored outcomes than had previously been available, especially in competing risks settings. We provide generic model-free learner-specific oracle inequalities bounding the finite-sample excess risk. The oracle efficiency results depend on the oracle selector and estimated nuisance functions from all steps involved in the transformation. We demonstrate the empirical performance of the proposed methods in simulation studies.