Pregnant women aren’t typically included in clinical trials, but that’s changing with COVID
The anatomy of a clinical trial depends, in many ways, on the anatomy of its participants. Drug development is a strange process which encompasses regulatory bureaucracy, and in the United States, a spectrum of players in the private and public spaces. The Food and Drug Administration’s mission statement is fairly clear: Establish the safety and efficacy of a pharmaceutical product. Those are the two formative pillars that can catapult an experimental substance to regulatory authorization.
But that leads to an inevitable question: safe and effective for which parts of the population? In the case of the coronavirus pandemic, it’s an issue that looms large for groups that are regularly underrepresented in clinical trials—especially pregnant women. And the nature of a global outbreak has forced drug developers to find ways to incorporate a wider swath of the population into their studies.
Medical experts tell Fortune that while the pandemic has led to ad hoc processes for having pregnant women involved in clinical trials, it may not have lasting impacts on the overall landscape for drug studies because this is such a vulnerable population.
“The tricky situation that they put us into is that pregnant women were not included in the trials that evaluate the efficacy of these COVID vaccines,” says Ashley Roman, director of maternal fetal medicine at NYU Langone Health.
But having as many women as possible, while pregnant or after giving birth, receive vaccines—which have overwhelmingly been proved to be safe and effective—will be critical to the goal of achieving herd immunity that protects everyone.
Why pregnant women aren’t common in clinical trials
The FDA is straightforward on its website: “In general, pregnant women are excluded from drug development clinical trials; however, in certain situations, it may be scientifically and ethically appropriate to include pregnant women in a clinical trial.”
It’s not a revolutionary concept. A pregnant woman’s biology isn’t the same as that of someone who isn’t pregnant, and making sure no harm is done to an expectant mother or the fetus is a crux of responsible drug development. But with caution comes tradeoffs: Sometimes, women just can’t get treatments which might help them or participate in the clinical studies that lead to those therapies’ approval. It’s a delicate balance and nothing new, but an issue which the COVID pandemic has highlighted in earnest.
While some are calling for more hard data on why exactly pregnant women are excluded, others find the threats of legal liability for clinical trial investigators and drug developers, the ethical dilemma of potential medical harms, and hesitancy on the part of pregnant women strong enough to continue to exclude them.
“There always is some degree of unknown when administering a new drug or a new vaccine to pregnant women,” says Roman, who specializes in high-risk pregnancies and is on the front lines of the COVID vaccination effort for that specific demographic. “We have a good sense of how the placenta works, and how things cross the placenta and can affect the fetus. Our understanding isn’t perfect. So there always is a small potential of harm.”
That potential harm is why clinicians, and regulatory bodies, are so cautious about recruiting pregnant women. There are extra steps to that process compared with those who aren’t pregnant.
How COVID could shift the dynamic
“There is currently no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta,” according to the Centers for Disease Control. “However, data are limited about the safety of COVID-19 vaccines for people who are pregnant.”
Making that data a bit less limited will rely on the efforts of the vaccine makers themselves—and that presents a shift in how these clinical trials are conducted in the face of a pandemic.
“During pregnancy, we had to make informed decisions or relatively uninformed decisions based on limited data about whether or not we could give certain medications to pregnant women that otherwise were being given to treat COVID and people who are not pregnant,” says Roman, referring to drugs such as Gilead’s remdesivir that can treat serious COVID illness.
“We had to do a deep dive and see whether these medications that have never been used on pregnant women could work for other indications and closely evaluate how they work, and then maybe make an educated decision about whether they could be used,” she adds.
In January, the World Health Organization still had not issued broad guidance for vaccinating pregnant women other than a recommendation for those who might be at particularly high risk for COVID. Initial trials from major manufacturers such as Pfizer, Moderna, and Johnson & Johnson didn’t enlist pregnant women.
Fast-forward to Feb. 18. Pfizer and partner BioNTech announced their first international study of their vaccine in healthy pregnant women over the age of 18. And for good reason.
“Pregnant women have an increased risk of complications and developing severe COVID-19, which is why it is critical that we develop a vaccine that is safe and effective for this population,” said Pfizer vaccine R&D senior VP William Gruber in a statement. “We are deeply thankful to the volunteers who are enrolling in the trial, and site investigators who are leading this work.”
Even launching such studies requires regulatory clearance under what’s called a developmental and reproductive toxicity (DART) analysis. This is the first step in the process to make sure a biopharmaceutical product isn’t toxic to a pregnant person or the fetus.
But follow-up is critical as well, which can make such studies more difficult to design. In the Pfizer study, a participant may be monitored for anywhere between seven and 10 months depending on whether she received the actual vaccine or a placebo.
Clinical trials often necessitate follow-ups such as these, but for pregnant women, there’s a bit of a twist since, as Roman says, pregnancy isn’t a permanent condition. Women who may not want to get a vaccine while pregnant could get one after giving birth, and in her experience, more than half of women she treats have opted to get a COVID vaccine regardless.
In the case of Johnson & Johnson’s one-shot vaccine, some experts say pregnant women who aren’t high-risk may want to refrain until we’ve gathered more information owing to its underlying technology, which is more conventional than Pfizer’s or Moderna’s.
But given that nearly 4 million children are born in the United States each year, ascertaining COVID vaccines’ safety for pregnant women will be a critical part of achieving herd immunity. Clinical trial designs are catching up to that reality in the midst of the pandemic.
That doesn’t mean that the change will be permanent given the vulnerability that pregnant women and their fetuses have. In the case of COVID, the disease can affect these women more severely, and there has been enough data to show that the current vaccines are safe in pregnant women. That may not be the case with other types of medicines, says Roman, which necessitates caution in recruiting pregnant women in clinical trials.
“When we look back at the history of medications, during pregnancy or even medications given outside of pregnancy, we’ve learned that certain medications have had inadvertent harm,” she says, pointing to therapies such as DES, which had been given to women to mitigate the possibility of miscarriage but had the side effect of increasing the chance of vaginal cancer in female fetuses.
“Based on history, and the fact that certain medications used during pregnancy with only the best of intent have inadvertently led to harm, it’s unclear to me about whether this is going to be one-off work we’re doing with COVID vaccines or whether it reflects more of a cultural change to include women earlier on in clinical trials,” says Roman.
More health care and Big Pharma coverage from Fortune:
- China promises to ease restrictions for visitors—but only if they get Chinese vaccines
- “A bitter failure”: Europe in turmoil over abrupt decision to halt the AstraZeneca COVID vaccine
- How the Biden administration plans to combat vaccine skeptics
- Commentary: One year later, we owe our COVID medical heroes a more efficient health care system
- Moderna has started testing its COVID vaccine on kids