Her view is echoed in numerous studies, including a recent review of tuberculosis outcomes among pregnant women. The authors found that there is an “urgent need for research in pregnant and postpartum women” in the area of pharmacokinetic safety and the ideal timing for treating latent tuberculosis.
Lyerly points out that the FDA doesn’t always approve drugs for every segment of the population, but the counterpoint is that pregnant women’s bodies function differently than do the bodies of women who aren’t expecting.
In 2001, when bioterrorism was regarded as a major threat, the American College of Obstetrics and Gynecology recommended amoxicillin for the management of pregnant women exposed to anthrax. In 2007 a small trial, which drew blood from pregnant women who were already taking amoxicillin, found that it was impossible to achieve therapeutic doses. “Your kidneys just metabolize it so quickly,” Lyerly says. “So that recommendation would have been completely wrong because of the lack of data.”
That trial is the type of research that Lyerly and Faden would like see more of. They refer to it as low-hanging fruit, where pregnant women who are already taking medication are monitored through blood or urine tests, for example, and then followed up with after the birth of their child.
“If we could simply make observational research a really high priority, we could get all kinds of useful, maybe not gold-standard findings, but useful findings about the outcomes that are associated with the different decisions physicians have to make,” says Faden.
Currently there is what Lyerly describes as a “weird myopia” that causes researchers to miss out on the opportunity to study pregnant women. The National Children’s Study, for instance, is studying the effects of the environment on children from before birth to when they turn 21.
“You have this cohort of 100,000 women who are taking medications and being exposed to things. There are health implications for women as well, and these aren’t being studied at all through the National Children’s Study,” Lyerly told me.
Second Wave has spoken to the researchers in charge of the project, and there may be some opportunities to study pregnant women post-hoc. Steven Hirschfeld, the director of the National Children’s Study, said that the current proposal, which is under external scientific review, is to collect prospective medication exposure information from approximately 50,000 women. “We also expect to collect retrospective historic exposure in about another 50,000 women,” he said.
Lyerly sees some cause for optimism that the situation is improving. She points to research into the use of drugs in children. Previously, children were, like pregnant women, therapeutic orphans of clinical trials and were treated like “small adults” for dosing recommendations. But two pieces of groundbreaking legislation, the Pediatric Research Equity Act (2003) and the Best Pharmaceuticals for Children Act (2002), have resulted in many labeling changes for the pediatric use of drugs.
Perhaps pregnant women could be headed in the same direction. The FDA is cautious about the inclusion of pregnant women in clinical trials and has said that it needs to be done on a case-by-case basis. “Pregnant women are often excluded from clinical trials and, when women become pregnant during a clinical trial, they are often discontinued from the trial. Thus, at the time a drug is approved, the decision to prescribe it to pregnant women usually is based on animal data with little or no human safety data,” an FDA representative said in an email. But the agency has made strides in the right direction, by launching in 2009 the Medication Exposure in Pregnancy Risk Evaluation Program to study the effects of prescription medication on pregnant women. The first full MEPREP study is evaluating the risk of birth defects in children whose mothers were prescribed sulfonamide antibiotics during their first trimester compared with mothers who were not taking antibiotics and mothers who were prescribed other antibiotics during their first trimester.
Trials seem to also be on the rise, with one 2012 study finding that 264 drug trials have been conducted specifically on pregnant women in the United States within two years of the study. The five most common drugs studied were vitamins, metformin, misoprostol, progesterone, and insulin.
Internationally, the European Medicines Agency published guidelines in 2005 that provide criteria for the “active surveillance for collecting post-authorization data” of pregnant women who have been exposed to new or established medical products. The World Health Organization and the Joint United Nations Program on HIV and AIDS released a guidance document for ethical considerations in HIV prevention trials. It specifically calls for the recruitment of pregnant women in such trials.
Lyerly was particularly excited when the National Institute of Allergy and Infectious Diseases began a trial testing the H1N1 vaccine on pregnant women, who are more vulnerable to the potentially pandemic virus.
Some studies have claimed that women would be reluctant to enroll in clinical trials because of fetal safety concerns. However, Lyerly, who was working at Duke, where the vaccine was being tested, said that women were “beating down the doors” to be registered.
One woman told Lyerly that she would rather be given the vaccine and examined closely than just have her doctor prescribe it to her and hope for the best.
“I felt like I was closely monitored and watched,” the woman told Lyerly. “I felt safer.”