Atkinson Anthony C, Duarte Belmiro P M, Pedrosa David J, van Munster Marlena
Department of Statistics, London School of Economics, London WC2A 2AE, United Kingdom.
Polytechnic Institute of Coimbra, ISEC, Department of Chemical & Biological Engineering, Rua Pedro Nunes, 3030-199 Coimbra, Portugal.
Contemp Clin Trials Commun. 2023 Apr 20;33:101140. doi: 10.1016/j.conctc.2023.101140. eCollection 2023 Jun.
The paper studies randomization rules for a sequential two-treatment, two-site clinical trial in Parkinson's disease. An important feature is that we have values of responses and five potential prognostic factors from a sample of 144 patients similar to those to be enrolled in the trial. Analysis of this sample provides a model for trial analysis. The comparison of allocation rules is made by simulation yielding measures of loss due to imbalance and of potential bias. A major novelty of the paper is the use of this sample, via a two-stage algorithm, to provide an empirical distribution of covariates for the simulation; sampling of a correlated multivariate normal distribution is followed by transformation to variables following the empirical marginal distributions. Six allocation rules are evaluated. The paper concludes with some comments on general aspects of the evaluation of such rules and provides a recommendation for two allocation rules, one for each site, depending on the target number of patients to be enrolled.
本文研究帕金森病序贯双治疗、双中心临床试验的随机化规则。一个重要特征是，我们从144名患者的样本中获取了反应值和五个潜在的预后因素，这些患者与即将纳入试验的患者相似。对该样本的分析为试验分析提供了一个模型。通过模拟对分配规则进行比较，得出因不平衡导致的损失以及潜在偏差的度量。本文的一个主要新颖之处在于，通过两阶段算法使用该样本为模拟提供协变量的经验分布；先对相关的多元正态分布进行抽样，然后将其转换为遵循经验边际分布的变量。评估了六种分配规则。本文最后对这类规则评估的一般方面进行了一些评论，并根据计划纳入的患者目标数量，为每个中心推荐了两种分配规则。
