Sanathanan L P, Peck C C
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857.
Control Clin Trials. 1991 Dec;12(6):780-94. doi: 10.1016/0197-2456(91)90041-j.
A randomized concentration-controlled trial (RCCT) is one in which subjects are randomly assigned to predetermined levels of average plasma drug concentration. These target concentrations can be achieved (within reasonable ranges) by an individualized pharmacokinetically controlled dosing scheme. The RCCT is designed to minimize the interindividual pharmacokinetic (PK) variability within comparison groups and consequently decrease the variability in clinical response within these groups. In this paper, we investigate the extent of improvement in sample size efficiency that can be gained from the RCCT design in comparison to the traditional randomized dose-controlled trial (RDCT) design. Our investigations involve both theoretical arguments and simulation studies, illustrated with data on PK and pharmacodynamic (PD) characteristics of the antiasthma drug theophylline. Aside from safety concerns that strongly suggest the use of RCCT for drugs with narrow therapeutic windows, sample size considerations favor the choice of RCCT in many situations, as shown in this paper.
随机浓度对照试验（RCCT）是指将受试者随机分配到预定的平均血浆药物浓度水平的试验。这些目标浓度可通过个体化的药代动力学控制给药方案（在合理范围内）实现。RCCT旨在使比较组内个体间的药代动力学（PK）变异性最小化，从而降低这些组内临床反应的变异性。在本文中，我们研究了与传统随机剂量对照试验（RDCT）设计相比，RCCT设计在样本量效率方面可提高的程度。我们的研究包括理论论证和模拟研究，并以抗哮喘药物茶碱的PK和药效学（PD）特征数据为例进行说明。除了安全问题强烈建议对治疗窗窄的药物使用RCCT外，如本文所示，在许多情况下，样本量的考虑也有利于选择RCCT。
