General characteristics and reasons for the discontinuation of drug clinical trials in mainland China

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Quality assessment of paediatric randomized controlled trials published in China from 1999 to 2022: a cross-sectional study

“…Most of the RCTs were initiated by tertiary hospitals, which is consistent with the distribution of economic prosperity, but there is still a large uneven geographical distribution of the sponsors and the research institutions. Additionally, most of the studies analysed paediatric clinical trials conducted in China, and the results were consistent with our previous study [ 26 , 27 ]. Another previous study also revealed disparities in the global distribution of orthopaedic RCTs, with the majority of the trials originating from the United States, the United Kingdom and Canada, and this global disparity has not improved over the last decade [ 35 ].…”

“…In 2021, we analysed the general characteristics and identified the reasons for and factors associated with clinical trial discontinuation in mainland China. In that study, the common reasons for trial discontinuation were commercial or strategic decisions [84 (26.9%)] and futility/lack of efficacy [70 (22.4%)] [ 26 ]. In 2022, we analysed paediatric clinical trials conducted in China and reported that the current challenge was the further development of dosage forms suitable for children with special attention to neonates and premature infants and the improvement of the uneven geographical distribution of sponsors and researchers [ 27 ].…”