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

• Published in: PLoS medicine 2024-05, Vol.21 (5), p.e1004405
• Main Authors: Shankar, Mridula, Hazfiarini, Alya, Zahroh, Rana Islamiah, Vogel, Joshua P, McDougall, Annie R A, Condron, Patrick, Goudar, Shivaprasad S, Pujar, Yeshita V, Somannavar, Manjunath S, Charantimath, Umesh, Ammerdorffer, Anne, Rushwan, Sara, Gülmezoglu, A Metin, Bohren, Meghan A
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Breast feeding; Clinical trials; Clinical Trials as Topic; Data analysis; Decision Making; Ecosystems; Ethics; Female; Fetuses; Humans; Intervention; Lactation - psychology; Liability insurance; Maternal mortality; Medical innovations; Medical personnel; Medical research; Medicine and Health Sciences; Medicine, Experimental; Mixed methods research; Motivation; Obstetrics; Participation; Patient Participation - psychology; Patient Selection; Pharmaceutical industry; Pregnancy; Pregnant women; Pregnant Women - psychology; Qualitative research; R&D; Recruitment; Research & development; Research and Analysis Methods; Reviews; Social aspects; Social Sciences; Systematic review; Therapeutic applications; Vaccines; Womens health; Workers
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1004405

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. 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. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For