Department of Pharmacy Children' s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Clinical pharmacy Key Specialty Construction Project, Chongqing, China.
Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, China.
BMC Med Res Methodol. 2021 Nov 13;21(1):246. doi: 10.1186/s12874-021-01443-2.
Although discontinuation is common in clinical trials, no study has been conducted to analyse the current situation and reasons for the suspension or discontinuation of drug clinical trials in China. This study aims to analyse the general characteristics and reasons for the discontinuation of registered clinical trials in mainland China and to identify the associated factors.
We conducted a cross-sectional observational study of discontinued trials registered in the Drug Trial Registration and Information Publication Platform before March 31, 2020. All trials with a status of terminated or stopped recorded in the platform were classified as discontinued trials and included in the analysis. The basic characteristics of the discontinued trials were recorded, reasons for trial discontinuation were recorded and divided into 4 categories as drug development strategy, trial planning, trial conduct and studied drug. Pearson's chi-square test and fisher's exact test were used to compare the differences in reasons for discontinuation between neoplasm trials and non-neoplasm trials, and to examine the associations of trial characteristics with different reasons related to trials discontinuation.
Three hundred twelve discontinued trials were included in this study. The studied drugs were mainly chemical drugs [229 (73.4%)], and indications of the studied drugs were mainly neoplasms [77 (24.7%)]. Geographical location of the discontinued trials were mostly in northern [114 (36.5%)] and eastern [96 (30.8%)] China. Study type of the included trials was mainly bioequivalence studies [97 (31.1%)]. The most common reason for trial discontinuation was commercial or strategic decision [84 (26.9%)], followed by futility/lack of efficacy [70 (22.4%)]. The number of trial centers, sample size and whether participants had been enrolled were significantly associated with trial discontinuation (P < 0.05). Multiple center trials showed a higher rate of trial discontinuation due to trial conduct related reasons than single center trials (P < 0.05), trials with sample size > 500 showed a higher rate of trial discontinuation due to studied drug related reasons (P < 0.05), and trials enrolled participants showed a lower rate of trial discontinuation due to commercial or strategic decision and a higher rate of trial discontinuation due to studied drug related reasons than trials without enrolled participants (P < 0.05). Besides, neoplasm trials showed a higher rate of trial discontinuation due to poor recruitment and safety comparing with non-neoplasm trials (P < 0.05).
Trial discontinuation in China mainly occurred because of commercial or strategic decision and futility/lack of efficacy of the studied drug. Clinical trials with multiple centers and a large sample size may more likely be discontinued due to trial conduct related reasons such as good clinical practice. Discontinuation due to drug safety and lack of efficacy in multiple center trials with a large sample size deserves more attention to avoid resources wastes. Full communication with regulatory authorities such as Center for Drug Evaluation and research institutes to develop a feasible protocol is important for sponsors to avoid trial discontinuation due to protocol issues.
尽管在临床试验中停药很常见，但目前还没有研究分析中国药物临床试验暂停或停药的现状和原因。本研究旨在分析中国大陆已注册临床试验停药的一般特征和原因，并确定相关因素。
我们对 2020 年 3 月 31 日前在药品试验登记与信息公示平台上登记的已停药试验进行了一项横断面观察性研究。平台上记录的状态为终止或停止的所有试验均被归类为已停药试验，并纳入分析。记录已停药试验的基本特征，记录停药原因，并分为药物开发策略、试验计划、试验实施和研究药物 4 类。采用 Pearson 卡方检验和 fisher 确切检验比较肿瘤试验和非肿瘤试验停药原因的差异，并检验试验特征与不同停药相关原因之间的关联。
本研究共纳入 312 项已停药试验。研究药物主要为化学药物[229（73.4%）]，研究药物的适应证主要为肿瘤[77（24.7%）]。已停药试验的地理位置主要在中国北部[114（36.5%）]和东部[96（30.8%）]。纳入试验的研究类型主要为生物等效性研究[97（31.1%）]。最常见的停药原因为商业或战略决策[84（26.9%）]，其次为无效/疗效不佳[70（22.4%）]。试验中心数量、样本量和是否入组参与者与试验停药显著相关（P<0.05）。多中心试验因试验实施相关原因导致停药的比例高于单中心试验（P<0.05），样本量>500 的试验因研究药物相关原因导致停药的比例较高（P<0.05），入组参与者的试验因商业或战略决策导致停药的比例较低，因研究药物相关原因导致停药的比例较高（P<0.05），而未入组参与者的试验则因商业或战略决策导致停药的比例较高，因研究药物相关原因导致停药的比例较低（P<0.05）。此外，与非肿瘤试验相比，肿瘤试验因招募不佳和安全性较差而导致停药的比例较高（P<0.05）。
中国的试验停药主要是由于商业或战略决策以及研究药物的无效/疗效不佳。多中心、大样本量的临床试验可能更容易因临床试验实施相关原因（如良好的临床实践）而停药。多中心、大样本量临床试验因药物安全性和疗效不佳而停药应引起更多关注，以避免资源浪费。与药品审评中心等监管机构充分沟通，制定可行的方案，对于申办方避免因方案问题导致试验停药非常重要。
