N-of-1 trials, single participant trials in which multiple treatments are sequentially randomized over the study period, can give direct estimates of individual-specific treatment effects. Combining n-of-1 trials gives extra information for estimating the population average treatment effect compared with randomized controlled trials and increases precision for individual-specific treatment effect estimates. In this paper, we present a procedure for designing n-of-1 trials. We formally define the design components for determining the sample size of a series of n-of-1 trials, present models for analyzing these trials and use them to derive the sample size formula for estimating the population average treatment effect and the standard error of the individual-specific treatment effect estimates. We recommend first finding the possible designs that will satisfy the power requirement for estimating the population average treatment effect and then, if of interest, finalizing the design to also satisfy the standard error requirements for the individual-specific treatment effect estimates. The procedure is implemented and illustrated in the paper and through a Shiny app.
翻译:Nof-1试验,即单个参与人试验,在研究期间按顺序随机进行多种治疗,可以直接估计个别治疗的效果。合并一试验提供了额外资料,用以估计与随机控制试验相比的人口平均治疗效果,并提高个人特定治疗效果估计的精确度。在本文件中,我们提出了一个设计Nof-1试验的程序。我们正式确定了确定一系列Nof-1试验样本规模的设计组成部分,提出了分析这些试验的模型,并利用这些模型得出样本规模公式,用以估计人口平均治疗效果和个别治疗效果估计的标准错误。我们建议首先找到可能的设计,以满足估计人口平均治疗效果的动力要求,然后,如果有兴趣的话,最后敲定设计,以满足个人特定治疗效果估计的标准错误要求。这一程序在文件中并通过一个Shiny应用软件得到实施和说明。