Backgroud
The use of drugs during pregnancy is very common. Many pregnant women
are being treated for existing or newly occurring medical conditions,
including hypertension, diabetes, asthma, and
psychiatry1; It is estimated that in the last three
decades, 84 ~ 99% of women has taken medicines during
pregnancy2-4.The pregnancy and delivery rate continue
to rise after the implementation of the ”two-child policy” in China.
Statistical data from Shanghai showed that the proportion of severe
pregnancies increased year-over-year from 2015 to 2018, and the
incidence of pregnancy complications was up to
44.42%5. This may aggravate the problem of
administration of drugs in pregnancy to some extent.
Over the past few decades, investments in the development of drugs for
obstetric diseases have been very scarce. This severely limits the
ability of obstetricians to make evidence-based
prescriptions6. Therefore,bioethicist,
pharmacologists, regulators, and researchers have advocated to inclusion
of pregnant women in clinical trials to improve knowledge about the
safety, dose, and long term effects of the drug in pregnant
women7-10. In 1993, the National Institutes of Health
(NIH) recommended that pregnant women be included in the clinical
trial11. The U.S. Food and Drug Administration (FDA)
passed the Pregnancy and Lactation Labeling Rule (PLLR, Final Rule) in
2014 to replace traditional pregnancy drugs used by pregnant women. This
law is expected to support further development and implementation of
such drugs12. However, the insufficient number of
pregnant women participating in clinical studies and being excluded from
clinical trials are still common phenomena10,13.The
study by Stockmann, et. al., reviewed the characteristics of obstetric
studies registered at http://clinicaltrials. From 2007 to 2012, these
studies accounted for less than 10% of the total number of
registries14. A systematic evaluation in 2016 reported
that in all valid registered drug clinical trials, only 0.32% were for
pregnancy drugs, and even fewer (4.4%) clinical trials included
pre-planned pharmacokinetic studies15.
Although China has been working to develop regulations that comply with
international standards, drug supply in mainland China is still affected
by a backlog application or delay in the approval process until
201316. In recent years, the National Medical Products
Administration (NMPA) has implemented various measures to encourage the
approval of special drugs (new chemical entities or drugs for the unmet
medical need), and to accelerate the approval process of clinical trial
of new drugs17. In order to further promote drug
innovation and improve the efficiency of drug clinical trials, after 5
years revision, the Good Clinical Practice (GCP 2020) is
enacted18, and the special protection requirements for
pregnant women and fetuses were proposed in the Measures for Ethical
Review of National Biomedicine Research (2016)19.
However, there were no detailed methods or plans in those
documents20. So far, there is no publicly available
systemic study regarding pregnancy drugs in mainland China. Therefore,
we conducted a systematic survey of the clinical trial registration data
to determine the quantity, geographical distribution, sources of funding
and interested pharmacological areas of the clinical trials in pregnancy
drugs between 2013 and 2020, so as to provide an up-to-date data as the
reference for decision makers and other stakeholders to improve the
current situation.