Home » Women and Girls » Urgent call to develop strategies to include pregnant women in clinical trials

Anne Claire Marrast

Senior Medical Director, Medicines for Malaria Venture

Karim Traore

Senior Researcher at Malaria Research and Training Center,
International Centers for Excellence in Research Mali

Research into drugs for use during pregnancy has been largely neglected since the negative effects of thalidomide on foetal development became agonisingly clear. Aside from oral contraceptives, very few drugs have been tested, trialled and developed for pregnant women. As a result, pregnant women are left without treatment options, or are exposed to the unknown effects of medicines.

Illness during pregnancy can be devastating for mothers and newborns. For example, in the case of malaria, it can lead to miscarriage, pre-term birth, stillbirth, low birth weight, anaemia in the mother, and in severe cases it can be fatal. In response to this, global regulators have issued a call to action to include pregnant and breastfeeding women in clinical research. 

Pregnant women not included in clinical trials

A critical factor is that this population is not commonly included in clinical trials and while campaigners are eager to change this, they face ethical, cultural and biological challenges. 

Anne Claire Marrast is Senior Medical Director at Medicines for Malaria Venture (MMV), a product development partnership working with pharmaceutical and research institutions to conduct research and clinical development to provide antimalarial drugs for the populations most in need — young children and pregnant women. 

“With malaria in pregnant women, there are two issues,” explains Marrast. “Pregnant women are more prone to get malaria and develop acute illness so we need the right drugs to protect and treat them. And when women get malaria while pregnant, there can also be consequences for the foetus.” 

Ethics in clinical trials

Senior Researcher Karim Traore from the Malaria Research and Training Center of ICER (International Centre of Excellence of Research) Mali, says: “pregnant women should be included in clinical trials because they have a specific physiology.” 

“This can have an important impact on drug outcomes in the human body, so it is important to include pregnant women to generate reliable data and develop well-tolerated and efficacious drugs,” he says. 

With community-based, cultural and biological reasons cited for their exclusion from trials, he says efforts must be made to “overcome these barriers.” We need a shift in mindset about how to keep pregnant women safe, and the necessary capacity to ensure this within clinical trials. 

Traore continues: “I think the main reason pregnant women are excluded from clinical trials is that we do not have available data on the potential effects of drugs we are using in trials, so this is an issue and clinical researchers do not like to take any risk for the baby and mother.” 

Failure to advance relevant initiatives will continue to leave pregnant women and their unborn children vulnerable to the threat of malaria and other diseases.

“Current regulatory guidelines say clinical trials for new drugs should only be performed in pregnant women when there is no alternative available but in the case of malaria, for example, you may want to be prepared for the situation where this treatment fails because of resistance.” 

MMV and ICER Mali are already taking steps to ensure the inclusion of pregnant women in clinical trials. 

In addition, MMV and partners have set up a pregnancy exposure registry, MiMBa (Malaria in Mothers and Babies), to capture data on safety of antimalarials in all trimesters of pregnancy.* 

Marrast and Traore believe that academia, governments, industry, regulators, medical personnel and civil society organisations must do more to ensure that pregnant women are safely included in clinical trials for such drugs. For researchers, this means employing cutting-edge technologies to help de-risk compounds before they enter trials, providing greater confidence that the investigational medicine can be administered in pregnancy. 

Tackling health inequities

Competent and functional ethics committees must provide specific protections for pregnant women in clinical trials. 

Failure to advance relevant initiatives will continue to leave pregnant women and their unborn children vulnerable to the threat of malaria and other diseases. Malaria remains a major threat: According to WHO, in 2021, 13.3 million pregnant women were infected in sub-Saharan Africa — with more than 60% of cases occurring during the first trimester. 

“We know this has consequences on the foetus and the newborn while at the same time, we have limited malaria drugs for pregnant women,” says Traore. “Inequities remain in treating pregnant women for malaria.” 

Engaging global and local communities

He believes an important step in overcoming such issues is via community engagement, as well as gathering more data to overcome the fact that many drugs are not recommended for use during pregnancy. 

“It is ethical to include pregnant women in drug development trials to gather much-needed data for this patient group,” he adds. Marrast says, “We should know how to dose pregnant women and the drug’s safety for the mother and the baby. There is an urgent need for healthcare professionals to have clear guidance and recommendations on how to best treat this patient population.” 

Strategies such as the G7 Therapeutics and Vaccines Clinical Trials Charter (June 2021), the World Health Assembly’s Resolution on Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination (approved at the WHA in May 2022) and bodies like the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and Accelerating Innovation for Mothers (AIM) are in place to strengthen approaches to clinical trials for medicines. 

The emphasis is shifting towards protecting pregnant women through, and not from, research while abiding by internationally agreed legal, medical safety and ethical standards. 

Marrast concedes that researchers have not been good at enrolling pregnant women over fears of harming the foetus. “I think we should reverse that and ask: ‘what is the risk of not including pregnant women and not providing the right treatment for them and the foetus?’” 

*Key aspects of MiMBa, which means ‘pregnancy’ in Swahili, include: ensuring quality drug supplies for children and pregnant women; generating data on existing compounds to inform their use in pregnant women and neonates; developing new antimalarial medicines for pregnant women and neonates; and advocating for changes in drug development that promote the safe and earlier inclusion of pregnant women into clinical studies. 

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