Diabetes Researchers Excluding Younger Women?

In many drug studies, the risk of fetal harm is used to exclude women who are pregnant or might become pregnant.

Although the National Institutes of Health mandated that researchers stop routinely excluding women of childbearing age from studies, many studies show that women are still excluded from many trials, even when risk to the participant and fetus are relatively low. This practice can limit young women’s access to clinical trials and hinder understanding of how new drugs will affect women.

A recent study published online before print on April 18 in Diabetes Care looked at barriers to enrollment in clinical trials among women with type 2 diabetes who are pregnant, breastfeeding, or who may become pregnant. The researchers selected diabetes because it is widespread among women who may become pregnant.

A team from Penn State College of Medicine analyzed exclusion criteria from 700 type 2 diabetes drug trials dating back to 1995 and registered on ClinicalTrials.gov. All trials included at least some women between ages 18 and 40.

Exclusion criteria for women who could potentially criteria were fairly widespread, although they varied widely in how restrictive they were. Overall, they found that 59 percent of the trials had at least on exclusion criterion for women based on fertility. Most often, women were excluded if they were currently pregnant or breastfeeding. However more than 50 studies excluded all women who could potentially bear children and 29 trials required female participants to take repeated pregnancies throughout the trial. Some studies had particularly restrictive criteria, such as excluding women planning to donate eggs, requiring them to use two forms of contraceptives during and after the trial.

Until 2015, the Food and Drug Administration ranked medication’s risk of causing birth defects. Drugs trials in the highest risk category had the most restrictive criteria. However, the increase in exclusion criteria did not map to the level of risk indicated by ranking.

"There really wasn't a strong association in any direction with drug risk and trial limitations," said Alannah L. Phelan, a third-year medical student at Penn State College of Medicine and lead author of the study.

The team found that trials initiated by investigators in academic centers tended to be more restrictive, required more contraceptive use, and included fewer women than pharmaceutical company-initiated trials.

"There are still widespread restrictions placed on participation of women in clinical drug trials, often without justification," Richard S. Legro, MD, professor of obstetrics and gynecology and public health sciences at Penn State and co-author of the study. "Results from these trials may not be generalizable to the larger population. Up to half of pregnancies are unplanned, and we don't know what the effects of these drugs will be on women if they take them and conceive while on them or if they are pregnant."

Concerns about liability may prompt investigators to set higher-than-needed restriction criteria. While this is a legitimate concern, it does not supersede principles of equity and access in clinical research, the researchers wrote.