arXiv subjects

Bernard Sebastien

Publications and source records attributed to Bernard Sebastien.

5 recordsLinked to original sources

arXiv2026

Estimating treatment duration effects via clone-censor-weight: a breast cancer case study

In this work, we study the estimation of treatment duration effects in observational survival data, where treatment and covariate histories evolve over time and longer observed durations are only attainable among individuals who remain event-free and under follow-up, leading to immortal time bias under naive analyses. The cloning-censoring-weighting (CCW) framework provides a practical approach to emulate target trials of treatment duration strategies, but several methodological aspects remain insufficiently understood. We focus on static treatment duration strategies under two settings of increasing complexity: baseline confounding only, and confounding with time-varying covariates. We formalize the assumptions underlying CCW, with particular emphasis on treatment admissibility, relaxed intervention rules, and the distinction between artificial and natural censoring. We then compare several estimation approaches after cloning and censoring, including inverse probability of censoring weighting (IPCW), the G-formula, and doubly robust estimators, through simulation studies assessing robustness, variability, and sensitivity to censoring model misspecification. Finally, we apply the framework to a Breast Cancer cohort to emulate a target trial comparing 2 versus 5 years of adjuvant tamoxifen in early stage breast cancer. Due to the small number of events and limited support for the 2-year strategy, estimates are associated with substantial uncertainty. These findings highlight both the practical relevance and the limitations of CCW, and underscore the importance of sensitivity analyses in complex longitudinal observational settings.

stat.ME↗

arXiv2025

Calibrating confounding strength in sensitivity models for weighting estimators: a comparative review and a new method

Causal inference is only valid when its underlying assumptions are satisfied, one of the most central being the ignorability or unconfoundedness assumption. However, this hypothesis is often unrealistic in observational studies, as some confounding variables may remain unobserved. To address this limitation, sensitivity models for Inverse Probability Weighting (IPW) estimators, known as Marginal Sensitivity Models, have been introduced, allowing for a controlled relaxation of ignorability. A substantial body of literature has emerged around these models, aiming to derive sharp and robust bounds for both binary and continuous treatment effects. A key element of these approaches is the specification of a sensitivity parameter, referred to as the "confounding strength", which quantifies the extent of deviation from ignorability. Yet, determining an appropriate value for this parameter is challenging, and the final interpretation of sensitivity analyses can be unclear. We believe these difficulties represent major obstacles to the adoption of such methods in practice. Therefore, after introducing sensitivity analyses for IPW estimators, we review different strategies to estimate or lower bound the confounding strength, introduce a new method leveraging negative controls, provide a decision tree with guidelines to choose a suitable approach, and compare the methodologies in an in-depth simulation study.

stat.ME↗

arXiv2025

Treatment Effect Estimation in Causal Survival Analysis: Practical Recommendations

The restricted mean survival time (RMST) difference offers an interpretable causal contrast to estimate the treatment effect for time-to-event outcomes, yet a wide range of available estimators leaves limited guidance for practice. We provide a unified review of RMST estimators for randomized trials and observational studies, establish identification and asymptotic properties, and supply new derivations where needed. Our extensive simulation study compares simple nonparametric methods (such as unweighted Kaplan-Meier estimators) alongside parametric and nonparametric implementations of the G-formula, weighting approaches, Buckley-James transformations, and augmented estimators under diverse censoring mechanisms and model specifications. Across scenarios, classical Kaplan-Meier estimators (weighted when required by the censoring process) and G-formula methods perform well in randomized settings, while in observational data G-formula estimators remain competitive; however, augmented estimators such as AIPTW-AIPCW generally offer robustness to model misspecification and a favorable bias-variance trade-off. Parametric estimators perform best under correct specification, whereas nonparametric methods avoid functional assumptions but require large sample sizes to achieve reliable performance. We offer practical recommendations for estimator choice and provide open-source R code to support reproducibility and application.

stat.ME↗

arXiv2024

Sharp Bounds for Continuous-Valued Treatment Effects with Unobserved Confounders

In causal inference, treatment effects are typically estimated under the ignorability, or unconfoundedness, assumption, which is often unrealistic in observational data. By relaxing this assumption and conducting a sensitivity analysis, we introduce novel bounds and derive confidence intervals for the Average Potential Outcome (APO) - a standard metric for evaluating continuous-valued treatment or exposure effects. We demonstrate that these bounds are sharp under a continuous sensitivity model, in the sense that they give the smallest possible interval under this model, and propose a doubly robust version of our estimators. In a comparative analysis with the method of Jesson et al. (2022) (arXiv:2204.10022), using both simulated and real datasets, we show that our approach not only yields sharper bounds but also achieves good coverage of the true APO, with significantly reduced computation times.

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arXiv2022

A Critical Review of Methods for Real-World Applications to Generalize or Transport Clinical Trial Findings to Target Populations of Interest

Generalizability and transportability methods have been proposed to address the external validity bias of randomized clinical trials that results from differences in the distribution of treatment effect modifiers between trial and target populations. However, such studies present many challenges. We review and summarize state-of-the-art methodological considerations. We additionally provide investigators with a step-by-step guide to address these challenges, illustrated through a published case study. When conducted with rigor, such studies may play an integral role in regulatory decisions by providing key real-world evidence.

stat.AP↗