A total of 347 clinical trials with indications including "er" of infant and child were retrieved in Chinese or "adolescent" were screened for inclusion. Of these, 77 trials were excluded due to duplications and repeated registrations, and 11 trials have been suspended, 2 non-drug trials, and one trial with indications not for children were excluded. Finally, there were 256 trials included for data extraction and analysis, accounting for 2.61% of the total registered number as of January 9, 2020.
General characteristics of the trials with indications for children in China
The general characteristics of trials with indications for children in China were shown in Table 1. Considering the 75 multiple-center trials, the number of centers was 8(3 ~ 377), and the trial with 377 centers was an international multiple-center phase Ⅳ clinical trial. In addition, 11 of the 16 trials for which a data safety monitoring committee have been established were multiple-center clinical trials. Of the 256 trials, the initial registration date of the trial was from July 2, 2013 to January 7, 2020, and the first ethical approval date of the trials was from September 19, 2007 to December 26, 2019. By considering the first ethical approval date, the number and the phase of trials distributed in different years was shown in Fig. 1.
Table 1
General characteristics of 256 trials with indications for children in China
Items | Frequency (%) |
Trial status | |
Ongoing | 119(46.48 %) |
Completed | 137(53.52 %) |
Trial phase | |
Phase I | 18(7.03 %) |
Phase II | 20(7.81 %) |
Phase III | 35(13.67 %) |
Phase IV | 14(5.47 %) |
Bioequivalence | 160(62.50 %) |
Others | 9(3.52 %) |
Trial range | |
China | 247(96.48 %) |
International | 9(3.52 %) |
No. of centers | |
Single-centre trial | 181(70.70 %) |
Multiple-centre trial | 75(29.30 %) |
DMC had been establish | 16 (6.25 %) |
Insurance had been purchased | 98(38.28 %) |
A total of 67 trials (including 4 phase Ⅰ, 20 phase Ⅱ, 26 phase Ⅲ, and 11 phase Ⅳ trials) were conducted among children age ranging from 0 to 18 years. Ten trials included both adults and children as subjects, and 179 trials (including all 160 bioequivalence trials) included only adults as subjects. A simple regression model revealed that the overall average annual growth rate of the number of trials was 43.30% (P = 0.0000). As shown in Fig. 1, the number of trials included had been significantly increased since 2017. In addition, a simple regression model based on the number of phases I to IV trials showed an average annual growth rate of 22.12% (P = 0.001).
Geographical location of the trials with indications for children in China
The geographical distribution of the sponsors of the 256 trials was shown in Fig. 2. More than 40% of the sponsors were located in the eastern China. The geographical distribution of the principal investigator involved in the 256 trials was shown in Fig. 3, and the trial institutions were mainly distributed in the east, the north and the central China, with Beijing, Jiangsu and Shanghai as the major ones.
Distribution Of The Studied Drugs And Its Dosage Form
The types of research drugs involved in the 256 trials and the distribution of the main dosage forms were shown in Fig. 4. The drug types mainly included were the chemical drugs, accounting for 76.17%. Based on the age of indications, there were 102 drugs used for children under 18 years age, i.e. children-specific drugs (39.84%), in which 3 drugs were used for premature infants and newborns, namely caffeine citrate, porcine lung surfactant and hepatitis B vaccine, and 11 drugs were used for only infants. The remaining 154 (60.16%) drugs were indicated for both adults and children. Considering the dosage forms of the 195 chemical drugs, tablets were the main ones, followed by capsules, injections and granules. The other dosage forms were shown in Fig. 4 included syrup, powder, oral solution membrane and needle-free percutaneous injection administration system, respectively. All traditional Chinese medicine/natural drugs were special drugs for children, and their dosage forms mainly included granules and patches. Of the 40 kinds (15.63%) of biological products, 33 were specific drugs for children, mainly in the form of injections.
Distribution Of The Indications Of The Research Drugs
According to ICD-10, the organ system of diseases related to the indications was shown in Fig. 5. Among them, 92 drugs (35.94%) were indicated for infections, followed by neurological, psychiatric and respiratory diseases. Of the 92 clinical trials with indications to infection, 26 were digestive system infections and 22 were respiratory system infections.