# The federated trials approach; an opportunity for global collaboration in health emergencies

## TL;DR

Federated trials offer a way to quickly combine data from multiple clinical trials during health emergencies to support regulatory decisions.

## Contribution

The paper introduces federated trials as a novel approach for global collaboration during health crises, ensuring timely and robust evidence.

## Key findings

- Federated trials can support regulatory decisions through a rigorous conjoined analysis of combined data.
- Harmonizing protocols and data standards is essential for successful federated trials.
- Federated trials are a viable alternative in emergencies when traditional single trials are impractical.

## Abstract

The gold standard for providing confirmatory evidence to regulatory agencies is a single sponsor conducting a randomised, controlled clinical trial (RCT). But emerging situations like the mpox outbreak can complicate launching large, single, global trials that meet the needs of multiple stakeholders, including multinational funders and regulators.

Drawing on lessons from the mpox outbreak, we propose an alternative approach: the federated trial design. This approach ensures that individual trials launch quickly and that a rigorous, prespecified, conjoined analysis using combined data supports joint regulatory decisions. Early engagement with regulatory agencies is crucial to arranging such a conjoined analysis.

Federating trials can support regulatory decision-making when they include a prespecified conjoined analysis that is sufficiently rigorous. Essential steps include harmonising individual trial protocols, aligning data standards, and arranging for a single Data Monitoring Committee to review a combined, multi-trial analysis.

The classical single-trial approach remains the gold standard, but investigators should consider federated trials in emergencies that complicate conducting single trials. In such crises, investigators need to explain clearly why standalone evidence from participating RCTs is not obtainable. The federated trials design cannot replace the classical design, but can provide timely, robust evidence in crises such as public health emergencies.