Background Master protocols leverage a common trial infrastructure for launching multiple sub-studies. Translational research aims to progress scientific discoveries toward public health impact, which depends on establishing an intervention’s efficacy, effectiveness in real-world conditions, and successful strategies for implementation. While master protocols have been designed to improve the efficiency of clinical trials as sub-studies addressing a particular disease, their application with effectiveness-implementation hybrid studies is yet to be explored. The aim of this study was to develop recommendations for adapting mater protocol methods for effectiveness-implementation research.

Methods A method of consultation with translational research networks was undertaken between January and December 2024. Consideration was given to the requirements for service providers to engage in translational research, and how master protocols could support effectiveness-implementation hybrid sub-studies. The underlying rationale for potential adaptations is provided with reference to implementation frameworks, discussion of advantages and disadvantages, and summary recommendations.

Results Recommendations are proposed on establishing common trial infrastructure, aims and hypotheses, data collection, control groups, adaptive elements, and eligibility criteria. By leveraging cross-sectoral partnerships, co-producing research and dissemination, and incorporating adaptive elements, master protocols may offer a promising approach for accelerating progress along the translational research pipeline.

Conclusions The adaptation of master protocols for hybrid sub-studies could enable evidence-based interventions to be more effectively implemented in routine care settings. The feasibility of master protocols for effectiveness-implementation research is yet to be tested, and further development in this area is needed to trial the proposed methodology.