英国欧洲分子生物学实验室David Ochoa课题组揭示与临床试验停止原因相关的遗传因素。2024年7月29日，《自然—遗传学》杂志在线发表了这项成果。

研究人员应用自然语言处理技术对28561项，在未达到终点前停止的临床试验的自由文本原因进行分类。随后，研究人员根据治疗假设和靶点特性背后的证据对这些分类进行了评估。研究人员发现，在缺乏来自人类群体或基因改造动物模型的强有力遗传证据的情况下，试验更可能因疗效不足而停止。

此外，如果药物靶点基因在人类群体中高度受限且在组织中广泛表达，则某些试验更可能因安全原因而停止。这些结果支持了人类遗传学在药物发现项目靶点评估中的日益重要作用。

研究人员表示，许许多药物发现项目启动后，只有少数能够顺利完成临床试验并获得批准。以往研究表明，人类遗传学对治疗假设的支持增加了试验进展的可能性。

附：英文原文

Title: Genetic factors associated with reasons for clinical trial stoppage

Author: Razuvayevskaya, Olesya, Lopez, Irene, Dunham, Ian, Ochoa, David

Issue&Volume: 2024-07-29

Abstract: Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to evaluate targets for drug discovery programs.

DOI: 10.1038/s41588-024-01854-z

Source: https://www.nature.com/articles/s41588-024-01854-z