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arXiv · 2610.15149

A Cosine-Projection Framework for Choosing Among Cox HR, D-RMST, and Average-Hazard Tests in Survival Trials

Abstract

The log-rank/Cox hazard-ratio test remains the standard approach for the primary analysis of randomized trials with time-to-event endpoints and is fully efficient under proportional hazards (PH). Two model-free alternatives that have recently gained attention are the difference in restricted mean survival time (D-RMST), a contrast on the time scale, and the more recently proposed ratio of average hazards (RAH), a contrast on the rate scale. Simulation studies suggest that the RAH-based test can outperform both under delayed treatment effects, but its efficiency has not been characterized analytically, and no unified framework explains how censoring and accrual affect the efficiency ordering among these tests. We show that all three statistics share a weighted-log-rank representation and derive their asymptotic relative efficiencies under local alternatives, including the first analytic efficiency results for the RAH-based test. Geometrically, each test defines a direction in a function space and the anticipated treatment effect defines a signal direction. A test's efficiency relative to the oracle test equals the squared cosine of the angle between these directions, so the asymptotic relative efficiency of any two tests is a ratio of squared cosines. Because censoring and accrual enter through an information weight, the framework shows how design choices can alter, and even reverse, the efficiency ordering. We illustrate the framework using the CheckMate 057 immunotherapy trial and corroborate the theoretical results through simulations spanning proportional- and non-proportional-hazards settings.

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BibTeXRIS

Xiang Meng, Lu Tian, Hajime Uno. 2026-10-10. A Cosine-Projection Framework for Choosing Among Cox HR, D-RMST, and Average-Hazard Tests in Survival Trials. https://arxiv.org/abs/2610.15149

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