© Laura Breiling

After the 2009 swine flu pandemic broke out, the US National Institutes of Health (NIH) launched a clinical trial of the new H1N1 vaccine specifically for pregnant women, who would be randomly assigned to receive one of two different dosages of the vaccine. The researchers filled their study quota quickly, and when Lyerly and Faden interviewed the volunteers, they learned that the women’s motivations for participating were astute and varied. Some wanted early access to a potentially lifesaving vaccine, others wanted to help advance scientific knowledge, and others thought that it would be safest to get the vaccine within the context of a clinical trial, in which they’d be carefully monitored. “Women were beating down the doors to get into the flu vaccine study,” Lyerly says. “The idea that pregnant women wouldn’t participate in a study is not true.”

But this willingness hardly matters if scientists don’t launch such studies in the first place. Lyerly, Little and Faden hope that their latest endeavour will help remedy this problem by encouraging more scientists to perform research with pregnant women and making it easier for them to do so. Their new, NIH-funded project focuses on HIV. Although preventing women from transmitting HIV to their children has long been a scientific priority, pregnant women are still largely excluded from trials of HIV-related drugs that could benefit their own health. In 2013, the troika set out to help close this research gap, joining with Anna Mastroianni, a legal scholar at the University of Washington, to launch a project they called PHASES (Pregnancy and HIV/AIDS: Seeking Equitable Study).

The four women are working to understand the reasons pregnant women are routinely excluded from these trials and to devise potential solutions. By the time the project wraps up in 2019, they plan to have produced a set of “practical, user-friendly” guidelines for studying pregnant women. Though their focus will be on HIV, the lessons they learn, and the guidelines they ultimately develop, should be relevant for scientists who want to study other illnesses. “Our goal is nothing less than coming up with an empirically grounded and consensus-based ethical and legal framework for how and when you can do research with pregnant women,” Little says.

They will also highlight specific strategies for gathering data on pregnant women in an ethically defensible but scientifically rigorous manner. Although scientists can and should study expectant mothers who have already made the choice to take certain medications, tracking their pregnancy outcomes and drawing their blood to study how the drugs are being metabolised, these opportunistic studies have limitations. (Among them that it can take decades to find and enrol enough women to draw significant conclusions.)

Conducting a traditional clinical trial ­– the gold standard in medicine – is trickier, but not impossible, especially if scientists think creatively. The PHASES team has highlighted a series of trials of tenofovir gel, which can protect women from HIV when applied inside the vagina, as one particularly innovative model.

To learn about the drug’s safety and dosing during pregnancy, a team of scientists based at the University of Pittsburgh gave a single dose of the gel to 16 pregnant women who had been previously scheduled to have Caesarean sections. The women received the drug just two hours before their deliveries, when the medication was unlikely to seriously harm a fetus. Once the researchers determined that pregnant women appeared to absorb the drug normally, and that very little of the compound reached the fetus, they pushed the exposure slightly earlier, giving the gel to women who were 37 to 39 weeks pregnant, and then to women who were 34 to 36 weeks along. Such studies will never be completely risk-free – nothing in clinical research or medicine is – but by being slow, deliberate and patient, researchers can minimise the chance of harm.

New laws could also help nudge drug companies in the right direction. The USA has spurred paediatric research by offering pharmaceutical companies extensions of their drug patents if they conduct studies with children; a similar strategy might also stimulate research with pregnant women. (As it currently stands, pharmaceutical companies have powerful disincentives to conduct such studies. If a medication that’s currently on the market turns out to cause birth defects, its manufacturer can argue that the compound was never approved for use in pregnant women. But if a company does conduct a small trial, labels a medication safe for use during pregnancy, and then the drug is later discovered to be dangerous? In that scenario, the pharmaceutical company has opened itself up to a barrage of lawsuits.)

There are small signs of progress. This autumn, the Council for International Organizations of Medical Sciences released a set of proposed revisions to its influential International Ethical Guidelines for Biomedical Research Involving Human Subjects. Among other changes, the new draft guidelines now emphasise the need for more research into the health needs of pregnant women and more clearly detail the level of risk that is acceptable in such studies. “The hope is that with more guidance, people will be less reluctant to conduct research,” says Annette Rid, a bioethicist at King’s College London and a member of the working group that revised the guidelines.

Meanwhile, pregnancy registries are continuing to track women who take certain medications, and several organisations and institutions have launched programmes to accelerate research. A handful of scientists are conducting full-fledged clinical trials with pregnant women, but the scale of the problem is huge, and experts say they need more funding for this work and more colleagues to join them in their efforts. In the meantime, pregnant women can seek advice on the risks and benefits of particular drugs from free teratology information services, and those who want to help advance scientific knowledge can volunteer for pregnancy registries. But until scientists do more controlled, rigorous studies, millions of women will be forced to muddle through, making medical decisions without the scientific evidence that many other patients take for granted.