Park Yeonhee, Nycklemoe Samuel
Department of Statistics, Sungkyunkwan University, Seoul, South Korea.
Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Stat Med. 2025 Jul;44(15-17):e70158. doi: 10.1002/sim.70158.
Adaptive randomization is a promising approach in clinical trials that aims to optimize patient outcomes by adjusting treatment allocation probabilities based on accumulating data. However, implementing adaptive randomization in group sequential trials, which include interim analyses for early stopping decisions, poses significant challenges, such as managing type I error inflation and ensuring robust statistical validity. This paper proposes Machine learning-assisted Adaptive Randomization for Group sequential trials based on Overlap weights (MARGO) as an innovative solution to these challenges. MARGO integrates machine learning (ML) models into the adaptive randomization process, allowing dynamic updates to randomization probabilities based on real-time predictions of treatment success. To control the overall type I error rate due to the covariate imbalance in group sequential trials, MARGO utilizes overlap weights (OW), which are employed to balance covariates across treatment groups, minimizing confounding and ensuring that the comparison between treatments remains unbiased. In our implementation, various ML algorithms are evaluated for their effectiveness in predicting treatment outcomes. Through extensive simulation studies, we demonstrate that MARGO not only enhances the flexibility and efficiency of group sequential trials but also maintains statistical rigor by effectively controlling type I error rates. Our results show that MARGO provides a more ethical and data-driven approach to patient allocation, potentially improving treatment success rates while preserving the integrity of the trial.
适应性随机化是临床试验中一种很有前景的方法,旨在通过根据累积数据调整治疗分配概率来优化患者预后。然而,在成组序贯试验中实施适应性随机化带来了重大挑战,成组序贯试验包括用于早期终止决策的期中分析,比如控制一类错误膨胀以及确保稳健的统计有效性。本文提出基于重叠权重的成组序贯试验机器学习辅助适应性随机化方法(MARGO),作为应对这些挑战的创新解决方案。MARGO将机器学习(ML)模型集成到适应性随机化过程中,允许根据治疗成功的实时预测动态更新随机化概率。为了控制成组序贯试验中由于协变量不平衡导致的总体一类错误率,MARGO利用重叠权重(OW),其用于平衡各治疗组之间的协变量,最大限度地减少混杂因素,并确保治疗之间的比较保持无偏性。在我们的实施过程中,评估了各种ML算法在预测治疗结果方面的有效性。通过广泛的模拟研究,我们证明MARGO不仅提高了成组序贯试验的灵活性和效率,还通过有效控制一类错误率保持了统计严谨性。我们的结果表明,MARGO为患者分配提供了一种更符合伦理且数据驱动的方法,有可能提高治疗成功率,同时保持试验的完整性。