Mixed-methods integration during data analysis in clinical trials of complex healthcare interventions: how is it done, and what can it do? Protocol for a systematic methodological review.

introductionThe importance of conducting qualitative research alongside clinical trials of complex healthcare interventions is well established. There are various ways in which these two methodologies can be combined in mixed-methods research, including integrating data and/or results from the qualitative and quantitative strands during analysis, using techniques such as joint displays. The potential benefits of integration during data analysis include understanding intervention mechanisms, reasons for variation in outcomes, ways of tailoring interventions to individuals and barriers and facilitators to implementation. However, integration during data analysis may rarely be undertaken in practice, and the extent to which integration can provide valuable insights appears to be underappreciated in the field.In this review, we aim to summarise current methods of integrating qualitative and quantitative raw data and/or results during analysis in clinical trials of complex healthcare interventions, and the yield of these different methods. Our specific research questions focus on (1) which integration techniques are used; (2) whether the results meet the study authors' aims and/or answer their research questions; (3) the insights obtained and/or meta-inferences generated from these techniques (classified as either global or specific, and as relational, predictive, causal, comparative or elaborative); (4) any relationship between these insights and/or meta-inferences and the integration technique used and (5) the quality of these studies. METHODS AND ANALYSIS: We will systematically search MEDLINE, Embase, PsycINFO, CENTRAL, CINAHL, Scopus and Web of Science, and manually search reference lists. We will include studies if they integrate, during data analysis, raw data and/or results from a clinical (randomised, non-randomised or single-arm) trial and an embedded or subsequent associated qualitative study of a complex, non-pharmaceutical healthcare intervention (where the effects on a health outcome were measured). Two independent reviewers will screen titles, abstracts and full texts and perform data extraction. We will develop a descriptive account of the data, including mapping the key characteristics of included studies and narratively reporting our findings in relation to each of our research questions. We will explore how integration was undertaken, what insights were obtained and/or meta-inferences generated, and whether and how these relate to the type of integration technique used. ETHICS AND DISSEMINATION: This study does not require ethical approval. We intend to publish our findings in a peer-reviewed open-access journal and to present our findings at national and/or international conferences. REGISTRATION: This protocol was registered with Open Science Framework on 22 October 2025 (ref osf.io/yxtb9).