Built-in Selection Bias in Proportional Hazards Models with Omitted Covariates: Simulation Evidence and Alternative Approaches

Statistics > Methodology [Submitted on 18 Jun 2026] Title:Built-in Selection Bias in Proportional Hazards Models with Omitted Covariates: Simulation Evidence and Alternative Approaches View PDF HTML (experimental)Abstract:In time-to-event analysis, the hazard ratio (HR) derived from the Cox proportional hazards (PH) model is the most commonly used and widely reported measure for assessing treatment effects. However, hazard ratios are non-collapsible due to their inherent conditioning on survival up to each time point. As a result, they are subject to built-in selection bias in the presence of unmeasured heterogeneity arising from omitted important covariates, even when these covariates are independent of the main exposure at baseline, as is the case in randomized controlled trials. This article aims to provide an overview of key findings from the literature on how unobserved heterogeneity, due to omitted covariates that affect the outcome, can bias the estimation of the treatment hazard ratio in standard proportional hazards models, even in randomized trials where treatment is assigned independently of such covariates. Through simulations, we evaluate the extent of bias in the semi-parametric Cox PH model and parametric PH model under various scenarios of unmeasured heterogeneity. We then compare these standard models to alternative approaches that either account for this issue or are considered robust to it. These alternatives include the hazard ratio estimated from frailty models, regression parameters from an Accelerated Failure Time (AFT) model, and survival differences between treatment groups estimated nonparametrically using Kaplan-Meier curves or based on a Cox model with time-dependent effect of the exposure. We illustrate the practical relevance of the explored alternatives through a real data application to a randomized controlled trial from the Radiation Therapy Oncology Group (RTOG 9202). References & Citations Loading... Bibliographic and Citation Tools Bibliographic Explorer (What is the Explorer?) Connected Papers (What is Connected Papers?) Litmaps (What is Litmaps?) scite Smart Citations (What are Smart Citations?) Code, Data and Media Associated with this Article alphaXiv (What is alphaXiv?) CatalyzeX Code Finder for Papers (What is CatalyzeX?) DagsHub (What is DagsHub?) Gotit.pub (What is GotitPub?) Hugging Face (What is Huggingface?) ScienceCast (What is ScienceCast?) Demos Recommenders and Search Tools Influence Flower (What are Influence Flowers?) CORE Recommender (What is CORE?) arXivLabs: experimental projects with community collaborators arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website. Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them. Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs.