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

Abstract

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-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.

Editorial: Comprehensive profiling cancer immunity with multimodal approaches for clinical management

“…Despite these developments, a critical knowledge gap persists concerning the identification and characterization of emergent immune-related pathways and biomarkers, alongside the elucidation of their underlying molecular mechanisms ( 9 , 10 ). Addressing this problem is crucial to further enhance the precision and efficacy of cancer clinical management and therapeutic targeting ( 11 ). Therefore, the continued exploration of these untapped aspects of cancer immunity represents an urgent imperative in contemporary oncological research.…”