Criteria Often Exclude Women of Childbearing Potential From Type 2 Diabetes Drug Trials

Exclusion criteria for clinical trials of type 2 diabetes medications that affect women of childbearing potential are frequently disproportionate to risk to the participant and fetus, according to data from a study published in Diabetes Care.

Clinical trials often exclude women of childbearing potential due to concerns about adverse fetal effects of treatment. Because of the high prevalence of diabetes among pregnant women, researchers examined the prevalence of fertility-related exclusion criteria in clinical trials for type 2 diabetes medications. They sought to determine whether these criteria are an accurate representation of type 2 diabetes drug risk.

Researchers searched ClinicalTrials.gov for clinical trials of type 2 diabetes medications that were phase 2 or 3 in the United States and enrolled participants aged 18 to 40 years.. They also compiled information about each trial, including enrollment rate, trial length, exclusion and inclusion criteria, trial sponsor, and pregnancy category of the drugs that were administered.

“The exclusion of women of childbearing potential from clinical trials, either outright or through multiple restrictive criteria, may be detrimental to clinical practice,” the authors wrote. “Diabetes is one of the most common chronic conditions complicating pregnancy, and novel medications will be used in pregnancy whether or not sufficient data are available.”

A total of 688 studies were included in the analysis. A majority of the studies (59%) included at least 1 fertility-related exclusion criteria, while 55% of trials excluded pregnant participants, and 44% excluded participants who were breastfeeding.

The researchers also found that clinical trials of medications with increased fetal risk did not have more restrictive criteria. Clinical trials of category C drugs, which have evidence of fetal risks in animals, were less likely to exclude pregnant participants compared with trials of category B drugs, which have no evidence of fetal risks (45.6% vs 69.8%; odds ratio [OR]=0.37; 95% CI,  0.20-0.65; P=.0005). Category C drug trials were also less likely to require contraceptive use than category B trials (29.9% vs 57.1%; OR=-0.32; 95% CI, 0.18-0.56; P=.001).

The authors speculated that the reason behind these disproportionate restrictions could be because of drug labeling, which may limit a trial’s ability to define fair protocols because of the significant variability in the teratogenicity of drugs within 1 category. Another reason could be concern about liability for the woman and her potential pregnancies.

“Future studies should investigate the effects of restrictions on women of childbearing potential on enrollment in studies of other medical conditions that commonly affect younger women such as rheumatologic disease, mood disorders, and epilepsy,” the authors noted. “Eliminating unnecessary barriers to recruitment will likely speed enrollment and increase generalizability of clinical trial data to women of all ages.”

Reference

1. Phelan AL, Kunselman AR, Chuang CH, et al. Exclusion of women of childbearing potential in clinical trials of type 2 diabetes medications: A review of protocol-based barriers to enrollment. Diabetes Care. 2016. doi:10.2337/dc15-2723.