The pregnant women as a drug orphan: a global survey of registered clinical trials of pharmacological interventions in pregnancy

Abstract

OBJECTIVE: To undertake a survey of the world's clinical trial registries to provide current data on the number, nature, funding source and geographical distribution of pregnancy drug trials (PDT). DESIGN AND SETTING: Comprehensive analysis of WHO-certified clinical trial registries. METHODS: Sixteen registries containing 301 538 trials (168 826 active in 2013-2014) were analysed to identify the numbers, location, funding sources, and areas of interest/development of PDTs. RESULTS: The percentage of PDTs varied from 0 to 7.4% across registries. Overall, just 0.32% (534) of all active registered studies were PDTs. The US registry (Clinicaltrials.gov) was the largest database, but contributed just 14% of all active PDTs. The majority of PDTs focused on anaesthesia/analgesia, preterm birth/tocolysis, labour induction, endocrine and hypertensive disorders. Less than 6% of active PDTs focused on maternal or fetal health as a specific primary outcome, and only 4.4% included a preplanned pharmacokinetic analysis of the trial medications. A third of all active PDTs involved repurposing of existing medicines for applications in pregnancy, whereas only three new investigational drugs had been developed for a pregnancy indication. Seven percent of all active PDTs identified were pharmaceutical industry-funded. Inter-disease comparisons identified a ~50-fold disparity in trial activity between pregnancy and other comparable areas. CONCLUSIONS: This study demonstrates unequivocally the marked under-representation of medication development, evaluation and safety trials in pregnancy. The likelihood that the current pharmaceutical landscape in pregnancy will improve in the foreseeable future is slim. Advocacy and increased awareness of the issue is necessary to achieve positive change. TWEETABLE ABSTRACT: Pregnant women are significantly under-represented in global clinical drug trials.