Shimizu Yosuke, Hanazawa Ryoichi, Sato Hiroyuki, Hirakawa Akihiro
Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Biostatistics Section, Department of Data Sciences, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
Contemp Clin Trials Commun. 2025 Feb 17;44:101450. doi: 10.1016/j.conctc.2025.101450. eCollection 2025 Apr.
One recommendation for the allocation ratio between multiple drugs and a shared placebo control group in platform trials (PTs) is to use a :1 allocation ratio for the placebo group relative to the drug group, where is the number of drug groups with ongoing patient enrollment during the trials. However, the practical utility of such unequal allocation ratios in PTs lacks adequate study.
We compared the performances of equal and unequal allocation ratios through simulations to imitate practical PTs using only concurrent controls and binary endpoints for hospitalized patients with infectious diseases. The operating characteristics, including the type I error rate, power of hypothesis testing, and total sample size, were evaluated.
In PTs, using an unequal allocation ratio (i) results in a considerable augmentation of the total sample size and prolongs the study duration when monthly patient enrollment is low, but (ii) the target power of hypothesis testing is often preserved compared to an equal allocation ratio, even when we incorrectly specify the drug and placebo group mortality rates assumed in the sample size calculation. The average power increase using an unequal allocation ratio relative to the equal allocation ratio per 100-patient increase in the placebo group was approximately 1.9 % in the selected scenarios of our simulation studies.
The results of the current study highlight the quantitative advantages and disadvantages of using unequal allocation ratios in PTs using only concurrent controls under the specific conditions assumed in our simulations and analyses.
在平台试验（PTs）中，关于多种药物与共享安慰剂对照组之间分配比例的一项建议是，安慰剂组与药物组的分配比例为 :1，其中 是试验期间有患者持续入组的药物组数量。然而，这种不平等分配比例在 PTs 中的实际效用缺乏充分研究。
我们通过模拟比较了相等和不相等分配比例的性能，以模拟仅使用同期对照和二元终点的住院传染病患者的实际 PTs。评估了包括 I 型错误率、假设检验效能和总样本量在内的操作特征。
在 PTs 中，使用不相等分配比例（i）在每月患者入组率较低时会导致总样本量大幅增加并延长研究持续时间，但（ii）与相等分配比例相比，假设检验的目标效能通常得以保留，即使我们错误地指定了样本量计算中假设的药物和安慰剂组死亡率。在我们模拟研究的选定场景中，相对于相等分配比例，安慰剂组每增加 100 名患者使用不相等分配比例时平均效能增加约 1.9%。
本研究结果突出了在我们模拟和分析所假设的特定条件下，在仅使用同期对照的 PTs 中使用不相等分配比例的定量优缺点。
