New clinical trial design in precision medicine: discovery, development and direction

作者：Xiao-Peng Duan, Bao‐Dong Qin, Xiao‐Dong Jiao, Ke Liu, Zhan Wang, Yuan‐Sheng Zang · 发表于：Signal Transduction and Targeted Therapy · 年份：2024 · DOI：10.1038/s41392-024-01760-0 · 被引用次数：170 · 研究领域：Cancer Genomics and Diagnostics、Statistical Methods in Clinical Trials、Single-cell and spatial transcriptomics

In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional "one-size-fits-all" trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the "Precision Pro", "Dynamic Precision", and "Intelligent Precision". This review would assist trial-r...