2009－2020年药物首次人体试验设计及结果文献分析

目的：全面描述药物首次人体试验的大致情况，总结首次人体试验设计与结果规律。方法：在PubMed上检索2009－2020年首次人体试验的文献，筛选出符合研究目的的文献，通过收集文献相关信息和数据，进行数据分析并总结。结果：本研究共纳入559篇首次人体试验文章，药物类型包括小分子药物（52.42%，293/559），大分子药物（45.62%，255/559）以及少量的细胞和病毒（1.97%，11/559）等。关于起始剂量的确定，不论是在大分子（23.86%，21/88）还是小分子（30.15%，41/136）中都主要以未见明显毒性反应剂量（27.68%，62/224）为主，其次是基于临床前研究（21.88%，49/224）以及最低预期生物效应水平（8.48%，19/224）等。剂量递增试验中50.19%（135/269）的研究使用传统标准3+3剂量递增方法，其次是加速滴定方法（7.06%，19/269），改进3+3方法（6.69%，18/269）等。结论：首次人体试验在研究设计内容和结果上具有一定的规律性，在后续试验中应科学设计首次人体试验，促进药物首次人体试验安全和有效开展。

Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.