DISCUSSION
The Drug Trial Registration and Information Publication Platform was started to operate in November 2012 but was not officially applied until 2013, and the clinical trials included in this study did not completely incorporate the clinical trials that obtained approval documents before 2012. Besides, the purpose of this study was to analyze the clinical trials of drugs with indications for children, and reflect the research and development situation of drugs for children in China, so we included studies with indications for children but apparently some of the studies were carried out in adults, although the drugs were indicated for children.
According to the retrieval results, there were still very few drugs (2.61%) for pediatric indications in the clinical trials of registered drugs that are currently carried out in China, and only 67 trials (26.17%) with children as subjects, only 102 trials (39.84%) with research drugs only for children. As a special and vulnerable group, recruitment and ethical issues make the conduction of clinical trials in children more challenging. How to further improve or innovate the technical methods of clinical trials, improve the use of efficient databases such as electronic medical record system, and strengthen the cooperation among industries, administrative departments, medical institutions, research doctors and subjects, to further promote the development of clinical trials of pediatric drugs and the application of data, has long been a problem of discussion [10]. On January 3, 2020, the State Drug Administration has issued the Notice of State Drug Administration on Guiding Principles for Issuing Real World Evidence to Support Drug R&D and Evaluation (Trial) (No.1, 2020)[11]. This pointed out that in areas of drug use for children, the use of real-world evidence is warranted to support the expansion of indications as this is also one of the situations where drug regulatory decisions may be applicable. This provides a new direction for research and development of drug use in children based on real-world evidence.
For a long time, the research and development of drugs and their preparations have mainly focused on adults and their associated diseases, and further development of drugs suitable for children of different ages has faced a great challenge [12]. In this study, the dosage forms of chemical drugs were still mainly tablets and capsules, which are commonly used by adults. Studies have shown that even small infants can take small doses of solid dosage forms, such as micro tablets [13]. In addition, other oral mucosal absorption dosage forms, such as orally disintegrating films, are also expected to become new dosage forms suitable for children [12]. Among the clinical trials included in this study, only montelukast sodium has the dosage form of orally soluble film. In terms of age for indications, of the 256 trials included in this study, 3 drugs were used for premature infants and newborns, and 11 drugs were used for infants only. Studies have shown that the incidence rate of off-label use of drugs in newborns was about 90%[14], and clinical trials in young children are facing greater ethical challenges, especially the sick newborns and premature infants, and might require new incentives or relevant policies to select the drugs that are mostly needed for research in trial design and development [15].
A great progress has been made in the study of drug use for children worldwide in recent years. Studies have shown that in the past 15 years, a total of 1,200 pediatric studies have been submitted to the U.S. Food and Drug Administration. More than 700 drug specifications have been revised and information on pediatric use has been provided. In addition, the failure rate of pediatric clinical trials has been decreased from more than 40% to about 20% [16]. In terms of quantity, the clinical trials of drugs with indications for children in China are increasing year by year, but excluded the bioequivalence trials, and the phases Ⅰ to osclinical trials were still less than 20 every year. In addition, there are still large regional differences between the sponsors and research institutions, with obvious advantages in the east and the north. How to further promote children’s clinical research based on the existing policies, narrow the differences between the east and the west, and develop specific drugs that are suitable for children, especially for young children, still requires the introduction of new policies, relevant incentives and technical guidelines. In general, the prospects in pediatric drug development are positive. The drug demand for a more flexible and individualized drug administration for children with significant improvement and development is warranted in the near future.