Women and babies are dying from inertia: a collaborative framework for obstetrical drug development is urgently needed

• Published in: American journal of obstetrics and gynecology Vol. 225; no. 1; pp. 43 - 50
• Main Authors: Roset Bahmanyar, Edith, Out, Henk J., van Duin, Marcel
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.07.2021
• Subjects: clinical trials with pregnant women; drug development; drug therapy; fetal growth restriction; legislative framework; obstetrical syndromes; obstetrics; pharmaceutical treatment; placental transfer; preeclampsia; pregnancy; pregnancy complications; preterm delivery; preterm labor; preterm premature rupture of membranes; research and development; small for gestational age; treatment during pregnancy; placental transfer; drug therapy; obstetrical syndromes; small for gestational age; pregnancy; drug development; preterm labor; pharmaceutical treatment; preeclampsia; treatment during pregnancy; preterm premature rupture of membranes; fetal growth restriction; clinical trials with pregnant women; research and development; legislative framework; pregnancy complications; obstetrics; preterm delivery
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2021.03.024

Obstetrical complications, often referred to as the “great obstetrical syndromes,” are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and clinicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes.