Factors influencing the participation of pregnant and lactating women in clinical trials: A mixed-methods systematic review

Background: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal–fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. Methods and findings: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. Conclusions: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women’s engagement, participation, and trust in such trials. Using a mixed-methods approach, Mridula Shankar and colleagues investigate the reasons why those who are pregnant and breastfeeding are under-represented in clinical trials.Why was this study done?: What did the researchers do and find?: What do these findings mean?: