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双变量秩和统计量的扩展在交叉设计中的应用,通过四个序列组比较两种治疗方法。

Applications of extensions of bivariate rank sum statistics to the crossover design to compare two treatments through four sequence groups.

作者信息

Kawaguchi Atsushi, Koch Gary G, Ramaswamy Ratna

机构信息

Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7420, USA.

出版信息

Biometrics. 2009 Sep;65(3):979-88. doi: 10.1111/j.1541-0420.2008.01170.x. Epub 2009 Jan 23.


DOI:10.1111/j.1541-0420.2008.01170.x
PMID:19173698
Abstract

This article describes applications of extensions of bivariate rank sum statistics to the crossover design with four sequence groups for two treatments. A randomized clinical trial in ophthalmology provides motivating background for the discussion. The bilateral design for this study has four sequence groups T:T, T:P, P:T, and P:P, respectively, for T as test treatment or P as placebo in the corresponding order for the left and right eyes. This article describes how to use the average of the separate Wilcoxon rank sum statistics for the left and right eyes for the overall comparison between T and P with the correlation between the two eyes taken into account. An extension of this criterion with better sensitivity to potential differences between T and P through reduction of the applicable variance has discussion in terms of a conceptual model with constraints for within-side homogeneity of groups with the same treatment and between-side homogeneity of the differences between T and P. Goodness of fit for this model can have assessment with test statistics for its corresponding constraints. Simulation studies for the conceptual model confirm better power for the extended test statistic with its full invocation than other criteria without this property. The methods summarized here are illustrated for the motivating clinical trial in ophthalmology, but they are applicable to other situations with the crossover design with four sequence groups for either two locations for two treatments at the same time for a patient or two successive periods for the assigned treatments for a recurrent disorder. This article also notes that the methods based on its conceptual model can have unsatisfactory power for departures from that model where the difference between T and P via the T:T and P:P groups is not similar to that via the T:P and P:T groups, as might occur when T has a systemic effect in a bilateral trial. For this situation, more robust test statistics have identification, but there is recognition that the parallel groups design with only the T:T and P:P groups may be more useful than the bilateral design with four sequence groups.

摘要

本文描述了双变量秩和统计量的扩展在两种治疗方法的四序列组交叉设计中的应用。眼科的一项随机临床试验为该讨论提供了具有启发性的背景。该研究的双侧设计分别有四个序列组T:T、T:P、P:T和P:P,其中T为试验治疗,P为安慰剂,对应于左眼和右眼的相应顺序。本文描述了如何在考虑两眼之间相关性的情况下,使用左眼和右眼各自的Wilcoxon秩和统计量的平均值来进行T和P之间的总体比较。通过减少适用方差对T和P之间的潜在差异具有更高敏感性的该标准的扩展,在一个概念模型中进行了讨论,该模型对相同治疗组的组内同质性以及T和P之间差异的组间同质性有约束条件。该模型的拟合优度可以通过对其相应约束条件的检验统计量进行评估。对该概念模型的模拟研究证实,与其他不具有此特性的标准相比,完全调用扩展检验统计量具有更好的功效。这里总结的方法在具有启发性的眼科临床试验中进行了说明,但它们适用于其他情况,即对于同一患者同时在两个部位进行两种治疗的四序列组交叉设计,或者对于复发性疾病的指定治疗的两个连续周期的交叉设计。本文还指出,基于其概念模型的方法对于偏离该模型的情况可能具有不令人满意的功效,例如当T在双侧试验中具有全身效应时,通过T:T和P:P组的T和P之间的差异与通过T:P和P:T组的差异不相似。对于这种情况,识别出了更稳健的检验统计量,但也认识到仅具有T:T和P:P组的平行组设计可能比具有四个序列组的双侧设计更有用。

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