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Designing cancer immunotherapy trials with random treatment time‐lag effect
Author(s) -
Xu Zhenzhen,
Park Yongsoek,
Zhen Boguang,
Zhu Bin
Publication year - 2018
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.7937
Subject(s) - lag , sample size determination , statistics , computer science , mathematics , piecewise , mathematical analysis , computer network
In some clinical settings such as the cancer immunotherapy trials, a treatment time‐lag effect may be present and the lag duration possibly vary from subject to subject. An efficient study design and analysis procedure should not only take into account the time‐lag effect but also consider the individual heterogeneity in the lag duration. In this paper, we present a Generalized Piecewise Weighted Logrank (GPW‐Logrank) test, designed to account for the random time‐lag effect while maximizing the study power with respect to the weights. Based on the proposed test, both analytic and numeric approaches are developed for the sample size and power calculation. Asymptotic properties are derived and finite sample efficiency is evaluated in simulations. Compared with the standard practice ignoring the delayed effect, the proposed design and analysis procedures are substantially more efficient when a random lag is expected; further, compared with the existing methods by Xu et al[15][Xu Z, 2017] considering the fixed time‐lag effect, the proposed approaches are significantly more robust when the lag model is misspecified. An R package (DelayedEffect.Design) is developed for implementation.