Contraception Requirements in Clinical Trials: Considerations From Studies on Sexually Transmitted Infections

Rigorous clinical trials are designed to ensure that study participants reflect individuals who may ultimately benefit from the treatment or intervention. Underrepresentation in trials leads to "data-free zones" in the safety and efficacy evidence base for commonly used and novel medications. This evidence gap leads to decisional uncertainty for patients, physicians and other clinicians, and regulatory bodies. Guidance from the National Institute of Allergy and Infectious Diseases from 2017 appropriately called for evidence from preclinical animal studies of reproductive toxicity to inform study eligibility requirements such as contraception. Since the first clinical trials of penicillin in 1941, individuals with pregnancy potential have been and continue to be underrepresented in clinical trials research, including studies designed to manage and prevent infectious diseases, such as sexually transmitted infections (STIs). A modifiable barrier to this underrepresentation is widespread eligibility criteria that include unnecessarily stringent contraception requirements. These requirements are based on 2 problematic assumptions: that all persons with pregnancy potential have a high and sustained risk of conception during the decades between menarche and menopause and that individuals are unable to avoid pregnancy for even a brief period (ie, exposure to a single-dose medication with a short half-life).