Smania G, Baiardi P, Ceci A, Magni P, Cella M
Consorzio per Valutazioni Biologiche e Farmacologiche, Pavia, Italy.
Dipartimento di Ingegneria Industriale e dell'Informazione, Università degli Studi di Pavia, Pavia, Italy.
CPT Pharmacometrics Syst Pharmacol. 2016 Jun;5(6):305-12. doi: 10.1002/psp4.12083. Epub 2016 Jun 1.
Alternative designs can increase the feasibility of pediatric trials when compared to classical parallel designs (PaD). In this work we present a model-based approach based on clinical trial simulations for the comparison of PaD with the alternative sequential, crossover, and randomized withdrawal (RWD) designs. Study designs were evaluated in terms of: type I and II errors, sample size per arm (SS), trial duration (TD), treatment exposures, and parameter estimate precision (EP). The crossover requires the lowest SS and TD, although it implies higher placebo and no treatment exposures. RWD maximizes exposure to active treatment while minimizing that to placebo, but requires the largest SS. SS of sequential designs can sometimes be smaller than the crossover one, although with poorer EP. This pharmacometric framework allows a multiscale comparison of alternative study designs that can be used for design selection in future pediatric trials.
与传统平行设计（PaD）相比，替代设计可以提高儿科试验的可行性。在这项工作中，我们提出了一种基于临床试验模拟的模型方法，用于比较PaD与替代的序贯、交叉和随机撤药（RWD）设计。研究设计从以下方面进行评估：I型和II型错误、每组样本量（SS）、试验持续时间（TD）、治疗暴露以及参数估计精度（EP）。交叉设计需要的样本量和试验持续时间最低，尽管这意味着更高的安慰剂和无治疗暴露。RWD在最大程度地增加活性治疗暴露的同时，将安慰剂暴露降至最低，但需要最大的样本量。序贯设计的样本量有时可能比交叉设计小，尽管参数估计精度较差。这种药理计量框架允许对替代研究设计进行多尺度比较，可用于未来儿科试验的设计选择。
