Facilitating participation in clinical trials during pregnancy

For decades, pregnant women have been routinely excluded from pharmaceutical trials because of widespread concern about drugs harming the fetus. Indeed, although medication use while pregnant or breastfeeding continues to be widespread,1 medication safety and efficacy data during pregnancy are still scarce. A 2011 review of 172 drugs approved by the US Food and Drug Administration from 2000 to 2010 found that 98% had an “undetermined” teratogenic risk in pregnancy, with 73% labelled as having no safety data in pregnancy.2 This striking lack of data means most pregnant women and their clinicians have to take decisions on starting or continuing medicines during pregnancy with very little or no evidence on safety or efficacy to guide their decision. UK confidential inquiries into maternal deaths repeatedly identify women who have died because medications have been stopped, or never started, in pregnancy as a result of unfounded safety concerns.3

In many ways, the covid-19 pandemic did not buck this trend, as nearly all vaccine and therapeutic trials excluded pregnant women. As a notable exception, the Recovery trial was one of few treatment trials for covid-19 that included pregnant women where appropriate, quickly addressing each barrier to inclusion to ensure participation was safe, following appropriate ethical and regulatory review. The trial was rapidly established in March 2020 using a pragmatic unmasked factorial design, and since then it has examined 20 treatments for covid-19 in patients admitted to hospital to assess their effect on all-cause mortality at 28 days after randomisation.4

After decades long efforts to promote inclusion of pregnant women in research, but particularly clinical trials,5 our successful experience in the Recovery …