As hormonal drugs to prevent pregnancy have evolved over the years, the US Food and Drug Administration (FDA) on Thursday drafted new guidance for drug developers on the recommendations for clinical trials designed to establish clinical effectiveness and safety for such products.
In terms of key considerations for clinical trial design features, the six-page draft begins by explaining the recommended enrollment criteria for nonpregnant, premenopausal woman in trials, which includes having regular menstrual cycles of between 21 and 35 days and engaging in vaginal intercourse at least once per month with a partner “who is not known to be subfertile or infertile,” among other criteria.
The draft also explains how although some contraceptives may not be as effective for women with increased body weight, “Sponsors should not place restrictions on body mass index (BMI) for trial enrollment. The trial population should include obese women (i.e., defined as BMI of at least 30 kg/m2), and the analysis plan should include a prespecified subgroup efficacy analysis in this population.”
As far as the type of trials to be run, FDA says randomization to placebo “is not feasible” (since women who enroll in such a trial may not desire a pregnancy) so, “Data from single-arm, open-label trials of at least 1 year’s duration are generally sufficient to establish efficacy and safety.”
Women over the age of 35 also should be enrolled in trials for safety determinations, FDA says.
“For a new molecular entity (NME), the division recommends that total drug product exposure include at least 20,000 menstrual cycles, with at least 400 subjects who complete the trial or trials,” the draft adds.
FDA also encourages sponsors to ensure trial subjects use an electronic daily diary to record whether intercourse occurred, the use of backup or emergency contraceptive methods, and any bleeding and/or spotting patterns. “Pregnancy outcomes should be collected and reported,” the agency adds.
In terms of safety considerations, the draft points to infrequent but well-known risks, such as venous thromboembolism. “The division may require postmarketing evaluation of risks such as venous thromboembolism if the benefits of a new drug product outweigh its risks, but additional characterization of the risk is required postapproval,” the draft says.
Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy: Draft Guidance for Industry