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.