Safer pregnancies: including mums-to-be in clinical trials will ensure evidence-based care, not guesswork
For decades, pregnant women have been routinely excluded from clinical trials because of concerns about trial drugs causing harm to the unborn baby. Often the only safety data on most drugs taken by pregnant women comes from decades of data obtained from women who took medications while largely unsure of whether or not they were safe.
According to Associate Professor Kirsten Palmer from the Department of Obstetrics and Gynecology at the School of Clinical Sciences at Monash Health and a member of the Monash Women’s Health Alliance, this striking lack of data means that pregnant women and their clinicians have to make decisions on starting or continuing medicines during pregnancy with only observational evidence on safety or efficacy to guide these decisions.
Besides the lack of safety data, little is known about how the changes women experience in pregnancy—including physiological, immunological, and hormonal changes—affect the metabolism and availability of different medications.
Associate Professor Palmer said that pregnant women are limited to using medications, such as blood pressure medication, that have been in use since the 1950s and 1960s.
“But many of these drugs have been superseded by much better ones, yet pregnant women either can’t take them because we don’t know whether they are safe, or they do take them because having an uncontrolled underlying medical disease can also pose a risk to the baby and or the mother,” she said. “It’s often a very difficult choice for the woman and her doctor.”
An example Professor Palmer cites is medications used to treat epilepsy. Pregnant women have not been included in any clinical trials.
“Does a woman, when she becomes pregnant, stop taking medications that can prevent her having an epileptic seizure, or does she take the medications not knowing the effect they might have on her or her baby?” she said.
While decades of observational data exist for many medications to guide clinicians’ advice on medication use, including pregnant women in clinical trials on new therapies would enable doctors to make safety recommendations based on evidence.
Following the Thalidomide tragedy, the US Food and Drug Administration (FDA) issued its most gender-restrictive guidance on clinical trials in 1977, recommending the exclusion of all women of childbearing age from early-stage clinical trials, regardless of their use of contraception methods.
This guidance was revised in 1993 to recommend better representation and therefore inclusion of non-pregnant women in early-stage clinical research. However, the FDA website still states, “In general, pregnant women are excluded from clinical research”.
A 2011 review of 172 drugs approved by the US Food and Drug Administration from 2000 to 2010 found that 98 per cent had an ‘undetermined’, or unknown, risk to the fetus, with 73 per cent labelled as having no safety data in pregnancy.
Under growing pressure to include pregnant women in clinical trials, in 2018, the US Food and Drug Administration (FDA) issued recommendations on scientific and ethical considerations to factor in when conducting clinical trials on this group, especially for industry sponsors. In 2020, the United States National Institute of Health Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) issued an implementation plan for working through the obstacles to include pregnant and lactating women in clinical research.
A 2024 review of drug policy in Australia and its alignment with the needs of expectant mothers, led by researchers from the University of Technology Sydney and published in The Lancet, argued that current “industry practices and regulatory approaches in Australia (e.g., a conservative approach to testing medicines in pregnant women) influence the availability of safety and efficacy data necessary for the licencing and funding of prescription medications used during pregnancy,” the authors said.
“Consequently, pregnant women may be prescribed medications outside of regulatory or funder-approved indications, posing risks for both prescribers and pregnant women and potentially compromising equitable access to medications.”
“As part of the Monash Women’s Health Alliance, we are working to advance progress on this front,” said Associate Professor Palmer. “We’re leading and contributing to a growing number of clinical trials to give pregnant women the opportunity to participate in trials to progress the development of new treatments for pregnancy-specific conditions, such as preeclampsia, postpartum haemorrhage, hyperemesis and fetal growth restriction.”
About Monash University
Monash University is Australia’s largest university with more than 80,000 students. In the 60 years since its foundation, it has developed a reputation for world-leading high-impact research, quality teaching, and inspiring innovation.
With four campuses in Australia and a presence in Malaysia, China, India, Indonesia and Italy, it is one of the most internationalised Australian universities.
As a leading international medical research university with the largest medical faculty in Australia and integration with leading Australian teaching hospitals, we consistently rank in the top 50 universities worldwide for clinical, pre-clinical and health sciences.
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