Development of Context-Appropriate Recruitment and Retention Approaches for Pregnant Women in the SAFIRE Clinical Trial Assessing Safety and Efficacy of Artemisinin-Combination Therapies: A Formative Research Protocol

Pregnant women, particularly those in the first trimester, have been historically excluded from clinical trials, resulting in substantial evidence gaps for the prevention and treatment of malaria in early pregnancy. Despite increasing calls from global health and regulatory bodies to include pregnant women in research, ethical, socio-cultural, and contextual challenges continue to impede their meaningful participation. Formative research is essential to understanding these challenges and informing trial procedures that are ethically robust and contextually appropriate. This study aims to explore stakeholder perceptions, beliefs, and decision-making processes related to early pregnancy and participation in clinical trials, to inform the development of culturally sensitive recruitment, retention, and community engagement strategies for the multi-country SAFIRE clinical trial on the safety and efficacy of artemisinin-combination therapies. Qualitative methods include in-depth interviews and focus group discussions with purposively sampled women of childbearing age, pregnant women, health providers and managers, community leaders, and other key health decision-makers. Data will be collected across five malaria-endemic countries in sub-Saharan Africa. A reflexive thematic analysis approach will be used, combining inductive and deductive coding within a collaboratively developed coding framework. Analysis will be informed by a Theory of Change to examine how identified barriers and facilitators may influence pathways to successful recruitment and retention. This protocol demonstrates how formative research can be systematically integrated into clinical trials to support the ethical inclusion of pregnant women.