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.