Including pregnant women in clinical trials safely: a necessity

May 28 is the International Day of Action for Women’s Health. We are highlighting PregTrial, a national initiative tackling the long-standing exclusion of pregnant and lactating women from clinical trials.

Pregnant and breastfeeding women have long been excluded from most clinical trials, allegedly to protect their health and that of their children. However, the unintended negative consequences of this exclusion are significant, and a growing number of physicians say it’s time for a change. Because without evidence-based data, pregnant women are left to choose between under-treatment and treatment without data —neither of which is safe.

Every day, Dr. Natalie Dayan, obstetric internist at the McGill University Health Centre (MUHC) and Scientist at the Research Institute of the MUHC, sees pregnant and lactating patients with cardiovascular conditions, mental health problems, or immune mediated diseases, like lupus and arthritis. Well aware of the challenges they face, she leads a national project called PregTrial, which aims to facilitate their safe inclusion in Canadian clinical trials.

“Some conditions affect a large population of women in their reproductive age. We need robust clinical trials to gather evidence on how to treat patients who are pregnant or lactating, otherwise they will remain undertreated for the entire reproductive period,” says Dr. Dayan.

Because of the lack of data to make informed decisions, expectant mothers and their healthcare providers often have to weigh the risks of taking a drug without clear safety or efficacy data during pregnancy versus the option of not treating or under-treating their condition.

“Neither option is optimal for the health of mother and baby. We know that untreated chronic diseases may sometimes cause more harm during pregnancy or lactation than a given medicine used to treat a given disease. This concept of incorporating the risk of untreated disease in our risk-benefit analysis of prescription during pregnancy and lactation is underappreciated,” adds Dr. Dayan.

Pregnant women, who face greater risks from infections like Zika, RSV, influenza and COVID-19, should also be included in trials for emerging infectious diseases.

However, Dr. Dayan insists that not all drugs should be tested in clinical trials in pregnancy. Inclusion should be considered for drugs that predominantly affect reproductive-aged women and that have not shown potential for teratogenicity—the ability to cause harm to the baby—in preclinical studies.

The story of thalidomide and how this contributed to the current status quo

Anti-nausea and immune-modulating drug thalidomide was widely used in the 1950’s and 1960’s to treat nausea of pregnancy, and was later linked to severe limb birth defects in children. This dramatic event created a lot of fear about drug use in pregnancy in the medical community and the population at large—a fear that still exists sixty years later. 

“Thalidomide was not tested to the standards that apply to drug trials today, and the paradox is that if it had been tested properly, this unfortunate event may not have happened. The good news is that the medical and scientific community learned from this event. Preclinical studies now test for serious harm or teratogenicity, and drug trials and the regulatory framework for new molecules are subjected to strict ethical and research frameworks,” explains Dr. Dayan.

The U.S. Food and Drug Administration recently endorsed a series of thoughtful recommendations for conducting trials that include pregnant women. To drive progress in Canada, Dr. Dayan is now working closely with Health Canada and various teams to support the development of safe, harmonized regulatory frameworks and guidelines.

While some fear and hesitation on the part of an expecting or lactating mother to participate in a clinical trial is understandable, Dr. Dayan emphasizes that the safest way to try a drug is in the controlled environment of a clinical trial, with close follow-up and monitoring of side effects. 

“Women tend to think of their baby’s health before their own and will sometimes be reluctant to take important medication for themselves. I tell them that a healthy mother is what their baby needs in the first place.”