FDA Tackling Tricky Topic: Drug Research on Pregnant Women

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By Greg Langlois

The FDA is seeking to strike a balance between protecting pregnant women and fetuses from unproven drugs while not shutting them out from treatments and helpful knowledge.

The FDA announced April 6 it is issuing draft guidance for industry on scientific and ethical considerations to address when determining whether to include pregnant women in drug development trials. About 4 million women give birth each year, the FDA says, citing the Centers for Disease Control and Prevention’s National Vital Statistics Reports.

How and when to include pregnant women in research trials has been a thorny issue regulators and the medical community have grappled with for years. Traditionally, the tendency has been to err on the side of caution, excluding pregnant women from drug research to protect them and fetuses from possible harm. But doing that prevents researchers from learning about how medications affect pregnancies, which itself can put women and fetuses at risk.

For example, more than 60 percent of pregnant women take a prescription drug during their pregnancies, but 90 percent of drugs the Food and Drug Administration approved from 1980 to 2000 didn’t undergo testing in pregnant women, a National Institutes of Health bioethics chief has said.


"[P]regnant women often use medically necessary drugs without a clear scientific understanding of the risks and benefits to themselves or their developing fetuses,” the draft guidance says.

At the same time, because drug labeling information for pregnant women is limited, if it exists at all, pregnant women and their physicians are often reluctant to continue treating chronic or acute conditions, the FDA says. This “in some cases may result in more harm to the woman and fetus than if she had been treated,” the draft guidance says.

It’s a longstanding issue, Society for Women’s Health Research (SWHR) Chief Executive Officer Amy Miller told Bloomberg Law in an April 6 interview.

“When a woman is pregnant and needs a therapeutic because of chronic disease, diagnosis of a new disease, or an accident, physicians and women are largely blind as to the impact those therapeutics could have on the fetus or the pregnancy,” Miller said. “So there is a reluctance of doctors and women to take drugs or treat disease, which is unfortunate because there are cases where untreated disease can cause harm as well.”

Cardiology is one well-researched area, she said. If a cardiovascular condition isn’t treated, “it can have drastic implications when it comes to the later stages of pregnancy and delivery,” she said.

“There’s this large gap in knowledge for women and physicians,” she said.

The FDA seeks comments on the draft guidance within 60 days after it appears in the Federal Register, which is scheduled for April 9.

Advocacy Groups Weigh In

SWHR, launched 28 years ago with the goal of making sure all women and people of color are included in NIH-funded clinical trial research, plans to comment on the FDA’s draft, Miller said.

Miller said she’s pleased the FDA and other regulators are addressing the issue, but that’s “step one.”

“There’s still another step, and that is encouraging the pharmaceutical industry itself to include pregnant women in research because as good as the science can be, and as thoughtful as the regulation I hope will be, we still have to have those companies willing to take this risk.”

The American College of Obstetricians and Gynecologists (ACOG) told Bloomberg Law the organization also is reviewing the FDA’s draft guidance and would be submitting comments on it.

ACOG has long advocated for removing pregnant women from the “vulnerable population” category under human subject regulations for groups considered to have a compromised ability to protect their interests and provide informed consent.

The group reiterated that stance in an April 2 submission to the Department of Health and Human Services’ Task Force on Research Specific to Pregnant Women and Lactating Women, created under the 21st Century Cures Act ( Pub. L. 114-255), a sweeping law passed in 2016 that boosted federal funding for medical research.

“Pregnant women have the same capacity for autonomous decision making as their nonpregnant counterparts, including decisions regarding whether to participate in appropriate research studies,” the group said in response to a task force request for information.

One provision in the draft guidance ACOG did take issue with is a requirement for a father’s consent if “the research holds out the prospect of direct benefit solely to the fetus.”

“ACOG feels that requiring this consent is not justified,” the group told Bloomberg Law in an email.

“In the absence of a few specific scenarios, requiring participation consent from a woman’s intimate partner is neither warranted nor ethically justified,” the group said in its recent NIH submission.

“Intimate partner consent could impose a barrier to participation for a woman, interfere with a woman’s choice of reproductive options, or interfere with a woman’s right to make independent decisions about her health care.”

FDA Advice

Drug sponsors should consider including ethicists when planning drug development programs and meeting with the agency early to discuss the prospect of including pregnant women during a study, the FDA’s draft guidance said.

Reasons to consider including pregnant women in trials include developing treatment options specifically for pregnant women, who undergo extensive physiological changes that can affect drug safety and efficacy, the FDA says.

“Filling the knowledge gaps regarding safe and effective use of drugs in pregnant women is a critical public health need, but one that raises complex issues,” the agency said.

To contact the reporter on this story: Greg Langlois in Washington at glanglois@bloomberglaw.com

To contact the editor responsible for this story: Randy Kubetin at rkubetin@bloomberglaw.com

For More Information

The draft guidance is available at http://src.bna.com/xGX.

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