Inclusion of pregnant and breastfeeding women in research – efforts and initiatives

Abstract

Pregnant and breastfeeding women have been rendered therapeutic orphans as they have been historically excluded from clinical trials. Labelling for most approved drugs does not provide information about safety and efficacy during pregnancy. This lack of data is mainly due to ethico-legal challenges that have remained entrenched in the post-diethylstilbestrol and thalidomide era, and that have led to pregnancy being viewed in the clinical trial setting primarily through a pharmacovigilance lens. Policy considerations that encourage and/or require the inclusion of pregnant or lactating women in clinical trials may address the current lack of available information. However, there are additional pragmatic strategies, such the employment of pharmacometric tools and the introduction of innovative clinical trial designs, which could improve knowledge about the safety and efficacy of medication use during pregnancy and lactation. This paper provides a broad overview of the pharmacoepidemiology of drugs used during pregnancy and lactation, and offers recommendations for regulators and researchers in academia and industry to increase the available pharmacokinetic and -dynamic understanding of medication use in pregnancy.

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

“…Prior to the Revitalization Act, women were largely excluded from participating in trials using pharmaceutical agents and there was growing concern that the process of drug development did not appropriately evaluate effects in female patients. 3 The systematic exclusion of women from research paralleled a similar exclusion of pediatric patients from clinical trials prior to the Best Pharmaceuticals for Children and Pediatrics Research Equity Acts of 1994. These efforts led to a dramatic shift in the culture of pediatric research.…”

“…With approximately 25% of pregnant women entering pregnancy with a medical condition or developing pregnancy-related morbidity, the rate of medication use in pregnancy has increased greatly. 3 In 2015, pregnant women were using on average four medications during pregnancy with almost half of them using four or more medications during pregnancy. [3][4][5] These factors place pregnant women at a disadvantage given that the vast majority of medications to treat nonobstetrical conditions were never tested in pregnancy.…”

“…3 In 2015, pregnant women were using on average four medications during pregnancy with almost half of them using four or more medications during pregnancy. [3][4][5] These factors place pregnant women at a disadvantage given that the vast majority of medications to treat nonobstetrical conditions were never tested in pregnancy. 6 The current state of research in pregnancy and the pattern of excluding pregnant women from drug trials is dismal at best and has not significantly improved even with recent improvements in the regulatory area.…”

Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects

“…Pregnant women are excluded from most drug trials . Pharmacokinetic studies involving pregnant women represent only 1.3% of all phase I trials registered through 2013 . The general exclusion of pregnant women from clinical trials has been predicated on concerns related to the potential foetal harms of medication used during pregnancy; this fails to consider the risk of withholding optimal therapies from pregnant women because of lack of data.…”

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

“…For ethical reasons, pregnant women have historically often been excluded from clinical trials in the drug development process, resulting in a gap of knowledge regarding both maternal and foetal drug exposure throughout gestation. However, recent reports on the importance of conducting pharmacological research in pregnancy and possible research strategies highlight that times are changing . To our knowledge, information on DAA exposure during pregnancy is currently limited to three conference abstracts.…”