No abstract

Background Research and development of pediatric drug faces many difficulties and pediatric clinical trials remain a challenge. Since 2011, a series of measures have been taken to encourage research, development of drugs for pediatric patients in China. In this study, we analyzed pediatric clinical trials conducted in China to provide reference for research and development of pediatric drugs and formulation of relevant policies. Methods We conducted a cross-sectional observational study of pediatric trials registered in the Drug Trial Registration and Information Publication Platform before Oct. 31, 2021. All trials that recruited children (under 18 years old as defined in China) were retrieved and general characteristics of the trials and the research drugs were extracted and analyzed. The data were extracted and statistically analyzed by excel 2010 and SPSS 22.0, respectively. Results There were 588 registered pediatric clinical trials, which accounted for 3.94% of the total registered trials. The overall average annual growth rate of the number of trials from 2013 to 2020 was 14.47% (P < 0.01). Of the 588 trials included, there were 312 trials (53.06%) with only children as subjects, 127 trials (21.60%) with research drugs only for children use, and the median of target subject number was 320 with the range of 8 to 600,000. The sponsors and the principal investigators were mainly located in the eastern and northern China. 325 trials were vaccine trials, and the dosage form was mainly injection. There were 98 non-vaccine biological product trials (mainly injections), 135 chemical compound drug trials (mainly tablets), 30 traditional Chinese medicine/natural drugs (mainly granules). Indications of the non-vaccine drugs were mainly diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism. Conclusion The number of pediatric clinical trials in China has increased these years. To further promote pediatric clinical trials and motivate pediatric appropriate drug marketing application and administrative approval, conducting large pediatric clinical trials, further development of dosage forms suitable for children with special attention to neonates and prematurity, and improving uneven geographical distribution of sponsors and researchers are the current challenges.

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.