Lack of reproductive aged women in COVID-19 trials has long-ranging effects

Women of reproductive age are often excluded from COVID-19 vaccine and treatment clinical trials, which could hinder their access to beneficial treatments, according to a study presented at the recent ACOG 2021 meeting.

“Pregnant and lactating females have been historically excluded from clinical trials, even when evidence of risk to the mother or foetus is lacking,” presented Kelly Kons, a third-year medical student at the Penn State College of Medicine, Hershey, Pennsylvania, US, on behalf of the investigators.

“Additionally, women of reproductive age are often required to prove adequate contraception which further diminishes the percentage of women able to participate [in these trials],” she said.

“This exclusion contributes to a significant absence of critical knowledge in the field of women’s health and prevents women from receiving potentially beneficial medical treatment, especially in the setting of a global pandemic,” she noted.

Using the US National Library of Medicine database, the investigators examined data from all COVID-19 vaccine and treatment clinical trials (90 and 495 trials, respectively) that were conducted between May and October 2020.

Pregnancy was an exclusion criterion in almost all vaccine trials (n=88; 97.8 percent), while lactation was an exclusion criterion in 73 trials (81.1 percent). Fifty-six trials (62.2 percent) required use of contraception. [ACOG 2021, poster presentation]

Type of vaccine (modality) was not associated with pregnancy exclusion but was associated with lactation exclusion and contraception requirement (p=0.01 and p<0.001, respectively). There was a higher likelihood of contraception requirement in trials that were initiated by pharmaceutical companies (p=0.03), though no significant association was noted for pregnancy or lactation exclusion. Location or trial phase was not associated with pregnancy or lactation exclusion, or contraception requirement.

Among treatment trials, pregnancy was an exclusion criterion in 70.7 percent (n=350) of trials and lactation an exclusion criterion in 54.3 percent (n=269), while 91 trials (18.4 percent) required contraception use.

Type of treatment was associated with pregnancy or lactation exclusion and contraception requirement (p<0.001). Pharmaceutical-sponsored trials had a higher likelihood of requiring contraception use (p<0.001), while trial phase was associated with pregnancy and lactation exclusion (p<0.001 for both) and contraception requirement (p=0.02).

“Despite evidence suggesting that pregnant women are at an increased risk of adverse outcomes from COVID-19, they were excluded from nearly all vaccine trials and a majority of treatment trials,” said Kons.

She pointed out that live-attenuated vaccines which are contraindicated during pregnancy had similar exclusion rates to inactivated and toxoid-based vaccines. This occurred even though influenza and Tdap vaccines are recommended during pregnancy, she continued.

“[Additionally,] many of the COVID-19 treatments being studied are approved for use in pregnant and breastfeeding individuals,” she said, noting that many of the trials using these treatments excluded pregnant or lactating women. “This highlights the gap between study inclusion and scientifically proven benefits of technologically-specific vaccination and treatment during pregnancy which is a disservice to women globally.”

She suggested that moving forward, inclusion criteria in clinical trials should be based on the specific experimental agent and not “theoretical risk.”

“[In the present setting,] females should be given the opportunity to consider the risks and benefits of a COVID-19 vaccine or treatment, and the autonomy to choose whether they should participate,” she concluded.