Related Experiment Video
Updated: Jun 20, 2026

Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Published on: June 5, 2020
Flexible modeling of the cumulative effects of time-dependent exposures on the hazard
Marie-Pierre Sylvestre1, Michal Abrahamowicz
1Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Que., Canada H3A 1A2.
Abstract:
Many epidemiological studies assess the effects of time-dependent exposures, where both the exposure status and its intensity vary over time. One example that attracts public attention concerns pharmacoepidemiological studies of the adverse effects of medications. The analysis of such studies poses challenges for modeling the impact of complex time-dependent drug exposure, especially given the uncertainty about the way effects cumulate over time and about the etiological relevance of doses taken in different time periods. We present a flexible method for modeling cumulative effects of time-varying exposures, weighted by recency, represented by time-dependent covariates in the Cox proportional hazards model. The function that assigns weights to doses taken in the past is estimated using cubic regression splines. We validated the method in simulations and applied it to re-assess the association between exposure to a psychotropic drug and fall-related injuries in the elderly.
Related Concept Videos
Hazard Rate
Pharmacodynamic Models: Additive and Proportional Drug Effect Model
Parametric Survival Analysis: Weibull and Exponential Methods
Weibull Distribution
The Weibull distribution is a flexible model used in parametric survival analysis. It can handle both increasing and decreasing hazard rates, depending on its shape parameter...
Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model
Assumptions of Survival Analysis
Pharmacodynamic Models: Linear Concentration–Effect Model
