In contemporary pharmaceutical practice, the mantra is “a drug should be used only if the benefits outweigh the risks, even though the risks may not be completely known.” To which you can really only say, “yikes!”
For pregnant women, receiving thoroughly tested and approved medication is harder than it is for most people because of the risks some medications pose to the fetus. But whether the benefits of including pregnant women in clinical drug trials outweigh the risks is up for debate.
At this point in time, the risks of excluding pregnant women from drug trials are simply too high, according to an editorial published in the Drug and Therapeutics Bulletin (DTB). Being denied medication, or worse, being given untested medication, is dangerous for the health of both mother and child.
For many patients, medication is not just a last resort, but one of the only options to treat or alleviate an ailment. In the U.S., the FDA’s Center for Drug Evaluation and Research (CDER), has strict guidelines for the development, testing, production, and distribution of pharmaceuticals.
Many drug researchers are reticent to take the risk of enrolling pregnant women in their trials, but an increasingly afflicted population of women of childbearing age who may require medication during pregnancy is driving demand and, perhaps, further testing.
“The impact of the increasing age and body mass index of the population has contributed to the proportion of women who require medication during pregnancy,” write the authors of the editorial.
A study from the Office for National Statistics in the UK found that four percent of women who had babies in England and Wales in 2011 were over the age of 40, up from just one percent of the women who gave birth in the 1990s.
“Some women develop health problems during pregnancy, and at least 40 percent take a prescription drug at some point,” reported researchers from the Coombe Women and Infants University Hospital in Dublin, Ireland, in 2010.
The Risks of Drug Testing During Pregnancy
While more information is almost always better, there's a difference between the blanket inclusion of pregnant women in clinical trials and well-supported, randomized trials conducted after it has been established that a medication is necessary and that it poses little to no risk for the mother and child.
“The bar is just higher with pregnant women because of the developing fetus being particularly vulnerable,” said Barbara Mintzes, Ph.D., an assistant professor in the School of Population and Public Health at the University of British Columbia. “As a blanket idea, it’s a bad idea.”
“Certainly there are treatments where it would make sense—where there is clear evidence that the condition needs drug treatment and the drug treatment can make a difference to the health of the mother and child,” Mintzes added. In those situations, a randomized controlled trial could be the answer.
However, because the health of both the mother and the fetus is at stake, the benefit of inclusion in the trial must outweigh the risks, ideally by a wide margin. The uterine environment is highly susceptible to change, and any disruption could have unknown effects.
Mintzes says antidepressants are a good example of a faulty model for the use of drugs during pregnancy. Because the bar for prescription is low, women who have mild depression may be receiving medication even when the difference in results between a placebo and medication may not be significant.
In a meta-analysis of antidepressant clinical trials, researchers from the McGill Journal of Medicine reported, “for most patients, the difference between drug and placebo was not clinically significant.” However, women are sometimes encouraged to stay on anti-depressants during pregnancy, or feel the need to keep taking them, Mintzes says. In this case, the benefits of the medication may not be worth the risk of side effects.
“Pregnancy is a natural state that has been ignored by the pharmaceutical industry for too long,” write the authors of the DTB editorial. The question is whether, as the editorial authors seem to suggest, it is time to treat pregnant women as a routine subgroup in clinical trials. Mintzes says this recommendation does not take into account the unique risks involved in pregnancy.
“There is the side where medications are clearly needed. If there is sufficient evidence of a real benefit, there is a rationale for trial,” Mintzes says. “There should be good evidence for interventions in pregnancy. There is that need for caution when there isn’t evidence of clear benefit either for the mother or the baby.”