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

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-sizefits-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.

An Organic Small Molecule as a Solid Additive in Non-Fullerene Organic Solar Cells with Improved Efficiency and Operational Stability

The use of additive is an effective approach to optimize the active layer morphology and improve the power conversion efficiency(PCE)of organic solar cells(OSCs).However,residual solvent additives always lead to undesirably compromise the stability of OSCs.In this work,an organic small molecule BBT-Cl was designed and used as a novel solid additive to partly replace solvent additive to fabricate highperformance OSCs.The synergistic effect of the dual additives on the optical property,morphology and photovoltaic characteristics of the PM6:Y6 based non-fullerene OSCs have been systematically characterized.The introduction of BBT-Cl could effectively enhance the crystallinity of the blend and promote charge extraction and transport.Consequently,the OSCs processed by the dual additives exhibit a high PCE of 17.73%,which is obviously higher than OSCs with CN additive(16.48%).Meanwhile,BBT-Cl based dual additives treatment has also been successfully introduced into another two non-fullerene OSCs to verify its general applicability.Furthermore,20%PCE aging is significantly prolonged from 720 min to 2880 min for the devices proceeded with the dual additives.This work highlights the great potential of solid additive in the fabrication of efficient OSCs with excellent stability.