Cook R J, Farewell V T
Department of Statistics and Actuarial Science, University of Waterloo, Canada.
Biometrics. 1994 Dec;50(4):1146-52.
There is currently a need for clinical trial methodology that allows formal consideration of toxicity responses. Since a complete evaluation of an experimental therapy addresses both relative efficacy and relative toxicity, general methods for handling bivariate response data are of interest. A procedure for sequentially analysing both efficacy and toxicity data is presented. The procedure is designed to allow early termination due to efficacy results, toxicity results, or both. The method is based on modified marginal sequential analyses, accounting for bivariate correlated responses and multiple analyses over time. The theory is presented in the context of normally distributed responses. Extensions to bivariate failure time data are indicated and an example from a kidney transplant study demonstrates the procedure.
目前需要一种临床试验方法，以便能够正式考虑毒性反应。由于对一种实验性疗法的全面评估既要涉及相对疗效，也要涉及相对毒性，因此处理双变量反应数据的通用方法备受关注。本文提出了一种对疗效和毒性数据进行序贯分析的程序。该程序旨在允许因疗效结果、毒性结果或两者而提前终止试验。该方法基于修正的边际序贯分析，考虑了双变量相关反应以及随时间的多次分析。该理论是在正态分布反应的背景下提出的。文中指出了对双变量失效时间数据的扩展，并且来自肾移植研究的一个例子展示了该程序。
