基于药物临床试验登记与信息公示平台和Clinicaltrials.gov的真菌药物临床试验现状分析

Current Status Analysis of Antifungal Drug Clinical Trials based on the Drug Clinical Trial Registration and Information Disclosure Platform and clinicaltrials.gov.

关键词:  真菌  临床试验  登记与信息公示平台  clinicaltrials.gov  分析

Key words:  fungal  Clinical trials  registration and information disclosure platform  clinicaltrials.gov  analyze

摘要:

目的 分析国内外真菌药物临床的现状及设计特点，为我国真菌药物临床研发提供参考。方法 检索中国药物临床试验登记与信息公示平台（www.chinadrugtrials.org.cn）和美国临床试验注册网站（clinicaltrials.gov），搜集2012 年 11 月 1 日至 2024 年 3 月 28日的真菌药物临床试验信息，使用wps office软件进行信息整理，纳入符合入排标准的临床试验进行分析。结果 中国药物临床试验登记与信息公示平台纳入194项试验，clinicaltrials.gov纳入196项。与clinicaltrials.gov相比，中国真菌药物注册临床试验现状呈现下述特点：（1）2018年起试验项目数量逐年上升且生物等效性试验/生物利用度试验增幅显著；（2）主要研究药物品种少（29 vs.59）且集中、新型真菌药物品种少（7 vs.16）；（3）未招募试验中健康受试者占比高（74.19% vs. 0.00%）。国内外试验方案设计呈现下述特点：（1）我国56.25%的侵袭性真菌感染试验使用科学性过高的诊断标准，即EORTC/MSGERC；（2）国内外60%的侵袭性念珠菌、念珠菌血症试验入组前经验用药时限比入组筛选的真菌培养与鉴定时间短；（3）国内外82.35%侵袭性念珠菌病试验排除了侵袭性深部念珠菌感染。结论 实施备案制后，释放新的临床试验机构促进了我国真菌药物临床试验的实施，但仍存在新型真菌药物研发不足、健康受试者招募难题，侵袭性真菌感染试验方案中的诊断标准、侵袭性念珠菌、念珠菌血症试验入组前经验用药时限、侵袭性深部念珠菌感染也存在完善和深入研究的空间。

Abstract:

OBJECTIVE This study aims to investigate the current status and design characteristics of antifungal drug clinical trials both domestically and internationally, providing valuable insights for the clinical development of antifungal drugs in China. METHODS Data were collected from the China Drug Clinical Trial Registration and Information Disclosure Platform (www.chinadrugtrials.org.cn) and the ClinicalTrials.gov website for antifungal drug clinical trials registered between November 1, 2012, and March 28, 2024. The data were organized using WPS Office software, followed by a descriptive analysis of eligible clinical trials. RESULTS A total of 194 clinical trials from the China Drug Clinical Trial Registration and Information Disclosure Platform and 196 trials from ClinicalTrials.gov were included in the analysis. The current status of registered antifungal drug clinical trials in China exhibits the following characteristics: (1) The number of trial projects has increased annually since 2018, with a notable rise in bioequivalence and bioavailability studies; (2) There are fewer investigational drug varieties (29 vs. 59), and the emergence of new antifungal drug varieties is limited (7 vs. 16); (3) A significant proportion of ongoing trials requiring recruitment involve healthy participants (74.19% vs. 0.00%). The trial design characteristics of domestic and international studies reveal the following trends: (1) In China, 56.25% of trials for invasive fungal infections employ overly stringent diagnostic criteria, specifically the EORTC/MSGERC guidelines; (2) In both domestic and international studies, 60% of trials for invasive candidiasis and candidemia have a shorter duration of empirical treatment prior to enrollment compared to the time required for fungal culture and identification; (3) A substantial 82.35% of trials for invasive candidiasis exclude cases of invasive deep-seated candidiasis. CONCLUSION With the implementation of the registration system, the introduction of new clinical trial institutions has facilitated the conduct of antifungal drug registration trials in China. However, challenges persist, including insufficient research and development of new antifungal drugs and difficulties in recruiting healthy participants. Moreover, there is potential for improvement and further research concerning diagnostic criteria in protocols for invasive fungal infection trial, the duration of empirical treatment prior to enrollment for invasive candidiasis and candidemia trials, and the management of invasive deep-seated candidiasis.