Bhattacharya Sudipta
Biometrics and Information Sciences, 101 ORD, One MedImmune Way, Gaithersburg, 20878, United States.
Contemp Clin Trials Commun. 2018 Mar 12;10:50-56. doi: 10.1016/j.conctc.2018.03.002. eCollection 2018 Jun.
Recurrent adverse events, once occur often continue for some duration of time in clinical trials; and the number of events along with their durations is clinically considered as a measure of severity of a disease under study. While there are methods available for analyzing recurrent events or durations or for analyzing both side by side, no effort has been made so far to combine them and present as a single measure. However, this single-valued combined measure may help clinicians assess the wholesome effect of recurrence of incident comprising events and durations. Non-parametric approach is adapted here to develop an estimator for estimating the combined rate of both, the recurrence of events as well as the event-continuation, that is the duration per event. The proposed estimator produces a single numerical value, the interpretation and meaningfulness of which are discussed through the analysis of a real-life clinical dataset. The algebraic expression of variance is derived, asymptotic normality of the estimator is noted, and demonstration is provided on how the estimator can be used in the setup of testing of statistical hypothesis. Further possible development of the estimator is also noted, to adjust for the dependence of event occurrences on the history of the process generating recurrent events through covariates and for the case of dependent censoring.
在临床试验中，复发性不良事件一旦发生，往往会持续一段时间；事件的数量及其持续时间在临床上被视为所研究疾病严重程度的一种度量。虽然有方法可用于分析复发性事件或持续时间，或同时分析两者，但到目前为止，尚未有人努力将它们结合起来并作为一个单一度量呈现。然而，这种单值组合度量可能有助于临床医生评估包含事件和持续时间的发病复发的整体影响。本文采用非参数方法来开发一个估计量，用于估计事件复发率和事件持续率（即每个事件的持续时间）两者的组合率。所提出的估计量产生一个单一数值，通过对一个实际临床数据集的分析来讨论其解释和意义。推导了方差的代数表达式，指出了估计量的渐近正态性，并展示了该估计量在统计假设检验设置中的使用方法。还指出了估计量进一步可能的发展方向，即通过协变量调整事件发生对产生复发性事件过程历史的依赖性以及相依删失的情况。
