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Health , US

New federal report calls out clinical trials for excluding pregnant women

by Erica Hensley April 10, 2024

When pregnant women get sick in the United States, they take medications that have been tested almost entirely on people who are not pregnant. Now, a federal report is pushing back on the long-held notion that pregnant people are “too vulnerable” to participate in clinical trials.

The report, released Wednesday by the National Academies of Sciences, Engineering and Medicine, says that pharmaceutical companies are wrong to exclude pregnant women and, most notably, women of color, from their research. Black women are nearly three times more likely than white women to die during or shortly after pregnancy.

While trying to avoid harming pregnant women, scientists are creating greater risks by allowing drug manufacturers to distribute medications without testing them during pregnancy, the report concludes.

“Because of the culture of exclusion, we are not dealing with the world as it exists today — we’re still stuck in 1960,” Margaret Riley, lead author of the report, told The Fuller Project in an interview. “Here it’s a real problem because we have this illusion that doing nothing is better than doing careful research…Like many issues impacting women, it’s done with the notion of protection that actually harms.”

The Food and Drug Administration, which approves medications before they go on the market, has no binding rules on including pregnant people in trials. The Centers for Disease and Control and Prevention, while advising pregnant patients to talk to their doctors about the safety of medications, says nobody really knows the answer regarding pregnancy. 

“We do not know very much about the effects of taking most medicines during pregnancy, because pregnant people are often not included in studies that determine the safety of new medicines,” according to the CDC’s website. “As a result, pregnant people and healthcare professionals have limited information about the safety of most medicines — especially newer medicines — in pregnancy.”

The report recommends that the FDA expand existing, ambiguous guidance by issuing regulations specifying that pregnant women be included in medical research. It also said Congress should provide incentives for pharmaceutical companies to do so. 

This is not the first time researchers have been criticized for failing to test drugs on women. In 1993, Congress directed the National Institutes of Health to ensure that an equitable number of women were included in clinical trials. But more than three decades later, the numbers are still askew. Last month, President Biden signed an executive order to advance research on women’s health.

The National Academies’ report is the first to deeply examine why pregnant women aren’t included in most clinical trials. It challenges legal, financial and cultural explanations.

“The reason we do clinical trials is because we don’t know. It’s not like you go from zero to 60 — you do it iteratively and carefully so you can understand (risk),” said Riley, an attorney who teaches bioethics and clinical research regulation at University of Virginia’s Law School. “Don’t let liability be the reason you don’t do it — it’s used as a placeholder for reticence overall.”

Other studies have found that people who finance and approve research are most worried about legal risk and costly delays to drug completion.  

But the new report counters that excluding pregnant women from clinical trials actually increases the risk of liability for drug producers that sell medications that have not been tested on that demographic. 

Researchers at the National Academies aggregated all known litigation against pharmaceutical companies by pregnant or postpartum women since 1963, when modern research regulations were first enforced. They found that not even one woman had filed a lawsuit contending she or her fetus was harmed by a clinical trial. But they found more than 1,000 cases of women suing drugmakers for harm from medications that were on the market.

This report is novel because it addresses a sort of unspoken rule in research circles — the unknown liability concern, says Irene Aninye, who is the chief science officer at the Society for Women’s Health Research and was not involved with the new research. “Every trial has its unknowns — it has its benefits and risks. But you plan and strategize for it to be as safe as possible for everyone involved and this should be applied to diverse populations as well.”

To be sure, there are considerable risks to testing medications on pregnant people, but the new report points out that those risks do not pose an overriding legal threat, and the known ethical and medical considerations can be figured out. 

“We are reaching a point where there is real interest in moving this ball forward by just getting rid of this sort of boogeyman of liability,” Riley said. “And finding a way to actually start giving women the information and research that they deserve.”

It is almost impossible for doctors and other healthcare providers to know which medications are — and are not — safe for pregnant women. Even medications that are otherwise safe can pose a real risk because bodies change during pregnancy. 

For example, the report quoted a woman who said she was advised to stop taking her rheumatoid arthritis medications during her second pregnancy. Her condition worsened. “By the time I hit my third trimester, I was struggling so significantly that my doctors advised me that the uncontrolled inflammation in my body was more of a risk to my baby than restarting my RA medications would be,” the report quoted her saying. She resumed taking the medications that she previously had been told to avoid, but said, “This was a very uncomfortable and difficult decision to make.”

Never was the problem in sharper relief than during the COVID-19 pandemic when, in the race to develop vaccines, pharmaceutical companies failed to include some of the people who were shown to be at the highest risk: pregnant women. 

When Moderna and Pfizer released their vaccines in December 2020, they did so without testing them on a single pregnant person. And though women comprised about half of the participants in those trials, the efficacy and safety data wasn’t broken down by sex. So while researchers confidently could say that vaccines were safe and effective in general — something years of real-world data now confirm — they could not say whether pregnant women would have different or more severe side effects than other adults. It wasn’t until nearly a year later that data were released on pregnant women. 

Ruth Faden, founding director of the Johns Hopkins Berman Institute of Bioethics, called the COVID-19 exclusion “unjustifiable.” The dearth of data “continues to impede the generalizability of clinical trial data and undermines the ability of pregnant and lactating persons to receive evidence-based health care,” she said at a meeting on pregnant women and drug trials. 

It’s not entirely possible to quantify the harm of neglecting to test medications on pregnant women. But limited data show that most trials exclude pregnant people. Even clinical trials that include pregnant women generally fail to collect and analyze separate data on them.

“It’s the default. It’s even worse than a default — it’s a default that isn’t even thought through,” Riley said. “There is such an assumption that you don’t want to include pregnant or lactating women … just saying nope, we’re not going to include them.”

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