Scholarship spotlight: Research addresses scientific knowledge gaps

University of Washington Professor of Law Anna Mastroianni has spent the better part of her legal career at the vanguard of cutting-edge research on… well, research.

More specifically, much of Mastroianni’s scholarly work targets legal and ethical barriers to inclusive clinical research practices. Her latest paper, “The Pathway Forward: Insights on Factors that Facilitate Research with Pregnant Women,” studies the thorny problems associated with exclusion of pregnant women in clinical trials. It is the continuation of a decadeslong research agenda with profound long-term public health implications.

Anna Mastroianni

“Somebody has to take on the legal issues, and there are not a lot of people doing that,” Mastroianni says. “You have to dismantle the black box a piece at a time.”

According to recent studies, while most women take at least one medication while pregnant, fewer than 3% of medications approved by the U.S. Food and Drug Administration have sufficient data to adequately inform doctors and women about their use during pregnancy.

“Pregnant women get sick and require medical intervention, but because they are usually excluded from research, we have little to offer them in terms of proven therapies,” Mastroianni says.

Information like this is not new, but widely accepted obstacles inhibit efforts to fill in knowledge gaps. Because of the nature of these roadblocks, Mastroianni says legal professionals must work with scientists, health care professionals and ethicists to find safe ways through them.

This subject is a longtime passion. Mastroianni, who co-authored her first scientific paper when she was 17 and whose parents were both obstetrician-gynecologists, set sights on making a different kind of impact beyond the lab.

She naturally gravitated toward law and public health, and she practiced corporate health law before joining the National Academies of Sciences, Engineering, and Medicine (NASEM) in 1992. There, she led a study funded by the National Institutes of Health that examined the exclusion of women in clinical trials, which at the time overwhelmingly comprised single white men. The study was just the tip of the iceberg, and she continued to dive deeper after joining the UW School of Law in 1996.

“The reason researchers recruited so-called ‘single white males’ is that they were seen as a readily accessible, scientifically homogeneous population,” Mastroianni says. “The assumption was that any findings would immediately translate to women and other groups. And we've discovered, of course, that is not the case.”

While today it may seem ludicrous to exclude an entire group of people from trials that could impact them directly, this largely remains the case with pregnant women despite an almost universal commitment among those studied to advancing women’s reproductive health.

The study — which is co-authored with Leslie Meltzer Henry, Sarah L. Wicks and UW Law alumnus Robert Franceschini ’17 — found obstacles at every step along the clinical pathway.

Among the challenges they heard, liability concerns coupled with ambiguous regulatory guidelines topped the list. The fact that calculating risk-benefit takes into consideration both the woman and fetus further complicates the analysis to the point that without explicit incentive or guidance on how to work through this complexity, decisions are made to move on.

But, Mastroianni argues, when you take a closer look at these points, it becomes clear that they are part of an established, accepted narrative that can — and should — be challenged.

If you're trying to have an action-informed agenda with long-term impact, you've got to show people the way.

“A lot of the same history that affected participation of women affects the participation of pregnant women in research,” she says. “We have to do better, especially because women may need medical interventions during pregnancy.

“Physicians are forced to rely on intuition instead of evidence, ultimately putting pregnant women and their fetuses at risk, and, from a legal perspective, subjecting physicians to liability for critical medical decisions.”

This issue has reached the highest levels of government. In 2016, Congress passed the 21st Century Cures Act, which established a “Task Force on Research Specific to Pregnant Women and Lactating Women to report on issues including development of safe and effective therapies for such women.”

Beyond what can be done at the federal level, there are actionable steps that can be taken now, such as: designing studies that account for the health needs of pregnant women specifically; providing for longer study windows; advancing institutional efforts to address the complexity of risk-benefit analysis; improving regulatory clarity; and several others outlined in the paper.

These are small but necessary steps toward closing the gaps, and Mastroianni hopes that in another 15 years, pregnant women and their physicians will have more comprehensive information they need to make informed decisions when it comes to reproductive health.

 “How can we remove the barriers for those researchers who are capable of working with this complex population and who are absolutely committed to doing this sort of work?” Mastroianni says. “You have to take the long view. And if you're trying to have an action-informed agenda with long-term impact, you've got to show people the way.”

Read “The Pathway Forward: Insights on Factors that Facilitate Research with Pregnant Women