Identifying treatment response subgroups in observational time-to-event data

Identifying patient subgroups with different treatment responses is an important task to inform medical recommendations, guidelines, and the design of future clinical trials. Existing approaches for subgroup analysis primarily focus on Randomised Controlled Trials (RCTs), in which treatment assignment is randomised. Furthermore, the patient cohort of an RCT is often constrained by cost, and is not representative of the heterogeneity of patients likely to receive treatment in real-world clinical practice. Therefore, when applied to observational studies, such approaches suffer from significant statistical biases because of the non-randomisation of treatment. Our work introduces a novel, outcome-guided method for identifying treatment response subgroups in observational studies. Our approach assigns each patient to a subgroup associated with two time-to-event distributions: one under treatment and one under control regime. It hence positions itself in between individualised and average treatment effect estimation. The assumptions of our model result in a simple correction of the statistical bias from treatment non-randomisation through inverse propensity weighting. In experiments, our approach significantly outperforms the current state-of-the-art method for outcome-guided subgroup analysis in both randomised and observational treatment regimes.

Neural Fine-Gray: Monotonic neural networks for competing risks

Time-to-event modelling, known as survival analysis, differs from standard regression as it addresses censoring in patients who do not experience the event of interest. Despite competitive performances in tackling this problem, machine learning methods often ignore other competing risks that preclude the event of interest. This practice biases the survival estimation. Extensions to address this challenge often rely on parametric assumptions or numerical estimations leading to sub-optimal survival approximations. This paper leverages constrained monotonic neural networks to model each competing survival distribution. This modelling choice ensures the exact likelihood maximisation at a reduced computational cost by using automatic differentiation. The effectiveness of the solution is demonstrated on one synthetic and three medical datasets. Finally, we discuss the implications of considering competing risks when developing risk scores for medical practice.

Imputation Strategies Under Clinical Presence: Impact on Algorithmic Fairness

Biases have marked medical history, leading to unequal care affecting marginalised groups. The patterns of missingness in observational data often reflect these group discrepancies, but the algorithmic fairness implications of group-specific missingness are not well understood. Despite its potential impact, imputation is too often a forgotten preprocessing step. At best, practitioners guide imputation choice by optimising overall performance, ignoring how this preprocessing can reinforce inequities. Our work questions this choice by studying how imputation affects downstream algorithmic fairness. First, we provide a structured view of the relationship between clinical presence mechanisms and group-specific missingness patterns. Then, through simulations and real-world experiments, we demonstrate that the imputation choice influences marginalised group performance and that no imputation strategy consistently reduces disparities. Importantly, our results show that current practices may endanger health equity as similarly performing imputation strategies at the population level can affect marginalised groups in different ways. Finally, we propose recommendations for mitigating inequity stemming from a neglected step of the machine learning pipeline.

DeepJoint: Robust Survival Modelling Under Clinical Presence Shift

Observational data in medicine arise as a result of the complex interaction between patients and the healthcare system. The sampling process is often highly irregular and itself constitutes an informative process. When using such data to develop prediction models, this phenomenon is often ignored, leading to sub-optimal performance and generalisability of models when practices evolve. We propose a multi-task recurrent neural network which models three clinical presence dimensions -- namely the longitudinal, the inter-observation and the missingness processes -- in parallel to the survival outcome. On a prediction task using MIMIC III laboratory tests, explicit modelling of these three processes showed improved performance in comparison to state-of-the-art predictive models (C-index at 1 day horizon: 0.878). More importantly, the proposed approach was more robust to change in the clinical presence setting, demonstrated by performance comparison between patients admitted on weekdays and weekends. This analysis demonstrates the importance of studying and leveraging clinical presence to improve performance and create more transportable clinical models.