新框架让临床试验更智能,兼顾监管要求与弱势群体疗效
Towards Regulatory-Confirmed Adaptive Clinical Trials: Machine Learning Opportunities and Solutions
- 先随机后自适应,分阶段高效分配患者
- 在真实数据上验证,提升治疗精准度和公平性
- 适合关注药物公平性与临床试验优化的研究者
随机对照试验(RCT)是评估新疗法效果的金标准。尽管治疗需通过严格的监管审查才能推广,但实际应用中仍面临诸多挑战:谁应接受治疗?真实临床价值如何?不同人群间疗效是否存在差异?本文提出两项新目标,将监管约束与整体及弱势群体的治疗政策价值相结合,提前回应上述问题。为此,我们设计了「先随机后增补」(RFAN)框架,包含标准随机部分与后续自适应部分,旨在安全高效地完成患者分组与治疗分配。基于因果推断与深度贝叶斯主动学习,我们提出了具体的实现策略,并在合成数据与半真实世界数据集上进行了实证评估。
原文摘要 · Abstract (English)
Randomized Controlled Trials (RCTs) are the gold standard for evaluating the effect of new medical treatments. Treatments must pass stringent regulatory conditions in order to be approved for widespread use, yet even after the regulatory barriers are crossed, real-world challenges might arise: Who should get the treatment? What is its true clinical utility? Are there discrepancies in the treatment effectiveness across diverse and under-served populations? We introduce two new objectives for future clinical trials that integrate regulatory constraints and treatment policy value for both the entire population and under-served populations, thus answering some of the questions above in advance. Designed to meet these objectives, we formulate Randomize First Augment Next (RFAN), a new framework for designing Phase III clinical trials. Our framework consists of a standard randomized component followed by an adaptive one, jointly meant to efficiently and safely acquire and assign patients into treatment arms during the trial. Then, we propose strategies for implementing RFAN based on causal, deep Bayesian active learning. Finally, we empirically evaluate the performance of our framework using synthetic and real-world semi-synthetic datasets.
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