The case for including pregnant women in COVID-19 clinical trials
Written by Dr Megan Rees, Chief Investigator, AustralaSian COVID-19 Clinical Trial, Respiratory and Sleep Physician, Royal Melbourne Hospital on behalf of the ASCOT pregnancy working group.
The effects of infection with COVID-19 during pregnancy are not fully described, however some evidence suggests that pregnant women are more likely to suffer from severe illness than women of the same age who are not pregnant. At this most critical stage of life, surely these patients (both mother and fetus) require the most precise, comprehensive, and up-to-date information about the disease effects and the best treatments.
At this time, the best treatment for COVID-19 during pregnancy is not known, to a large extent because pregnant women have been specifically excluded from most clinical trials. Despite the pleading of many leading obstetric and paediatric groups for pregnant women to be offered treatments within the close observation of a clinical trial setting (1) few trials have included pregnant women. During 2020 the number of clinical trials started for COVID-19 increased rapidly, however most excluded pregnant women and the proportion that did so has not changed over the pandemic.(2)
Clinical trials often exclude pregnant women from being participants. There can be several reasons for this, such as concern for the effects on the unborn child, but also additional costs that might occur because the offspring may need to be followed up after birth or the insurance premium for running the trial may increase. When pregnant women infected with COVID-19 are excluded from clinical trials the result is that they may miss out on potentially lifesaving therapies or be exposed to risks of unproven therapies without the balanced testing and close observation that is required for a clinical trial. If not tested in trials there will be less structured reporting of information about whether treatments work or are safe, which can in turn impact on treatment decisions for other pregnant women.
Given the scarce data that are available, the inclusion of pregnant women in therapeutic trials would increase knowledge of the efficacy and potential side-effects of candidate treatments and contribute to the development of a research framework for improved understanding of pregnancy and perinatal-associated transmission of the SARS-CoV-2 virus. The ASCOT investigators recognised that this important patient population should not be left out, so a group of expert physicians was brought together, which included specialists in paediatrics, obstetrics, infectious and respiratory diseases, most of whom are mothers themselves. This pregnancy working group has liaised closely with the Trial Steering Committee and the sponsor of the trial, the University of Melbourne, to be able to open the ASCOT trial to pregnant women.
Many of the treatments being tested for COVID-19 are already known to be safe in pregnancy such as convalescent plasma, aspirin, and enoxaparin. ASCOT is now able to offer participation to pregnant women for all medications and therapies that are already known to be safe in pregnancy. The modular study design of ASCOT allows pregnant women to be automatically excluded from treatments that are not known to be safe in pregnancy, while offering pregnant women the opportunity to participate in trialling a range of safe treatment options.
ASCOT provides pregnant women with clear messages in lay language on the potential benefits and risks of exposure to candidate drugs for the treatment of COVID-19 and pregnant women are given the right to make their own informed decision regarding participation. Mothers are most likely to have the greatest concern for the health of their newborn and are best placed to make the decision about trial participation. This offers pregnant women access to the most promising treatments, as well as providing valuable information for future pregnant women and their treating teams.
- Whitehead CL, Walker SP. Consider pregnancy in COVID-19 therapeutic drug and vaccine trials. The Lancet. 2020;395(10237):e92.
- Taylor MM, Kobeissi L, Kim C, Amin A, Thorson AE, Bellare NB, et al. Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action. The Lancet Global Health.