Efficient Semiparametric Estimation of Short-term and Long-term Hazard Ratios with Right-Censored Data

TL;DR

This paper develops efficient likelihood-based methods for estimating short-term and long-term hazard ratios in censored survival data, accommodating crossing hazards and time-dependent covariates, with proven statistical properties and practical validation.

Contribution

It extends the Yang and Prentice (2005) model to include covariates, providing asymptotically efficient estimation procedures with theoretical guarantees.

Findings

Methods perform well in simulations

Captured crossing hazards in cancer trial

Identified significant long-term genetic effects

Abstract

The proportional hazards assumption in the commonly used Cox model for censored failure time data is often violated in scientific studies. Yang and Prentice (2005) proposed a novel semiparametric two-sample model that includes the proportional hazards model and the proportional odds model as sub-models, and accommodates crossing survival curves. The model leaves the baseline hazard unspecified and the two model parameters can be interpreted as the short-term and long-term hazard ratios. Inference procedures were developed based on a pseudo score approach. Although extension to accommodate covariates was mentioned, no formal procedures have been provided or proved. Furthermore, the pseudo score approach may not be asymptotically efficient. We study the extension of the short-term and long-term hazard ratio model of Yang and Prentice (2005) to accommodate potentially time-dependent covariates. We develop efficient likelihood-based estimation and inference procedures. The nonparametric maximum likelihood estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Extensive simulation studies demonstrate that the proposed methods perform well in practical settings. The proposed method captured the phenomenon of crossing hazards in a cancer clinical trial and identified a genetic marker with significant long-term effect missed by using the proportional hazards model on age-at-onset of alcoholism in a genetic study.