# Could master protocols be adapted for effectiveness-implementation hybrid studies?

## TL;DR

This paper explores adapting master protocols for studies that combine testing real-world effectiveness with implementation strategies.

## Contribution

The paper proposes recommendations for adapting master protocols to support effectiveness-implementation hybrid studies.

## Key findings

- Recommendations include common trial infrastructure, adaptive elements, and cross-sector partnerships.
- Master protocols may help accelerate translational research by combining effectiveness and implementation.
- Feasibility of the proposed methodology requires further testing.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12874-025-02684-1.