Inclusion of women susceptible to and becoming pregnant in preregistration clinical trials in low- and middle-income countries: A proposal for neglected tropical diseases.

The Drugs for Neglected Diseases initiative (DNDi) aims to conduct research and development of new, improved, and patient-focused treatments for neglected tropical diseases (NTDs). DNDi’s goal is to address unmet medical needs in low- and middle-income countries (LMIC) where they are needed using the best regulatory approval strategy for effective, safe, and affordable new treatments. When NTDs affect women susceptible to and becoming pregnant (WoSuP), a major concern, shared by DNDi, is to ensure that there are available data to support the safety and efficacy of the treatments for these women and potentially for their babies.

WoSuP are female patients, sometimes very young, who have reached menarche and could become pregnant during treatment or during a clinical study or trial.

For several decades, there has been reluctance to include WoSuP in clinical trials because of the potential risk of exposing the fetus to investigational drugs. This has led to neglecting physiological differences between WoSuP and other adult populations.

This trend is, however, changing with arguments in favor of the ethical need to have appropriate data on new treatments in any population including WoSuP before regulatory approval. One of the systematic mitigating precautions taken to allow recruitment of WoSuP in preapproval clinical trials is the use of contraception. However, contraception is not always widely available, culturally allowed, followed, or effective in preventing pregnancy. Women might become pregnant during a clinical trial of a new treatment. The purpose of this paper is not to discuss the inclusion of already identified pregnant women but to envisage how to include WoSuP and provide them with access to innovative drugs, while acknowledging and mitigating the risk that they might become pregnant during the trial.

Understanding the existing limitations for the participation of WoSuP in clinical trials, DNDi suggests the use of appropriate measures to ensure that WoSuP are represented as far as possible in trials, in accordance with scientific and ethical standards.

This paper describes DNDi’s proposal, which is based on a benefit and/or risk assessment of participation versus nonparticipation of this population in clinical trials. The primary objective is to provide adequate and robust evidence of efficacy and safety in this population, while also considering the risks related to the NTD and alternative treatment landscape, and balancing these with possible embryo-fetal harm. Whether to include WoSuP or pregnant women at the time of the recruitment and whether to continue inclusion of women who become pregnant during clinical studies represent different situations. A safe ethical framework for the recruitment of WoSuP in clinical trials of new drugs against NTDs is the focus of this paper.