Penalized Likelihood Optimization for Adaptive Neighborhood Clustering in Time-to-Event Data with Group-Level Heterogeneity

TL;DR

This paper introduces a novel penalized likelihood framework that jointly performs patient clustering and shared-frailty survival modeling in hierarchical data, effectively uncovering latent subgroups with distinct risk profiles.

Contribution

It develops an adaptive spectral clustering method integrated with survival analysis to identify patient subgroups while accounting for group-level heterogeneity.

Findings

Successfully recovers latent patient clusters in simulations.

Identifies clinically meaningful subgroups in COVID-19 heart failure data.

Highlights hospital-level variability and comorbidities as risk factors.

Abstract

The identification of patient subgroups with comparable event-risk dynamics plays a key role in supporting informed decision-making in clinical research. In such settings, it is important to account for the inherent dependence that arises when individuals are nested within higher-level units, such as hospitals. Existing survival models account for group-level heterogeneity through frailty terms but do not uncover latent patient subgroups, while most clustering methods ignore hierarchical structure and are not estimated jointly with survival outcomes. In this work, we introduce a new framework that simultaneously performs patient clustering and shared-frailty survival modeling through a penalized likelihood approach. The proposed methodology adaptively learns a patient-to-patient similarity matrix via a modified version of spectral clustering, enabling cluster formation directly from estimated risk profiles while accounting for group membership. A simulation study highlights the proposed model's ability to recover latent clusters and to correctly estimate hazard parameters. We apply our method to a large cohort of heart-failure patients hospitalized with COVID-19 between 2020 and 2021 in the Lombardy region (Italy), identifying clinically meaningful subgroups characterized by distinct risk profiles and highlighting the role of respiratory comorbidities and hospital-level variability in shaping mortality outcomes. This framework provides a flexible and interpretable tool for risk-based patient stratification in hierarchical data settings.