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

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.

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Publication Details

Journal
EClinicalMedicine
Published
2026-02-25
DOI
https://doi.org/10.1016/j.eclinm.2026.103809
Primary Topic
Ethics in Clinical Research
Type
article
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article

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

Sujith A. Valiyaparambil, Sharon Nachman, Roberta Pereira Trefiglio, Josie Marshall et al.
EClinicalMedicine
Ethics in Clinical Research
article

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

Sujith A. Valiyaparambil, Sharon Nachman, Roberta Pereira Trefiglio, Josie Marshall, Najeh Daabek, Maria Figueroa, Matthew M. Hamill, Lu Zheng, Mayara Secco Torres Silva, Maria Pia Diniz, Kieron Seymour Leslie, Inge Christoffer Olsen, Grace M. Aldrovandi, Mario Delgado-Ortega, Jhoanna C. Roa, Matthias briel, Michèle Genin, Laetitia Guiraud, Lara A. Hosey, Isabelle Hoffmann, France Mentre, Kathie G Ferbas, Stefano Musumeci, Erica Telford, ROGER J. LEWIS, Faye Landsman, Franz König, Osilade Adewole, Alain Amstutz, Shahadah Bailey, Beatriz Grinsztejn, Jason Zucker, Caitlyn McCarthy, Skerdi Haviari, Axelle Dupont, Alexander L. Greninger, Jillian Laroche, Shawn Chiambah, Bridget Makhlouf, Edmund Capparelli, Luiz Carlos Pereira Junior, Laurence Toutous-Trellu, Xavier N. de Lamballerie, José Valdez Ramalho Madruga, Maxime Hentzien, Cheryl Day, Alpha Diallo, José Henrique Pilotto, Stanford Chimutimunzeve, Maria José Rolón, Gilles Peytavin, Nathalie Strub-Wourgaft, Carlee Moser, David Smith, Justin Ritz, Carolina Perez, Dimie Ogoina, Léa Vitu, William Fischer, Lauren Mabe, Keyla de Almeida Macedo, Christine Johnston, Pooja Saha, Jade Paris, Maelle Coupez, Sabine Yerly, Alexandra Calmy, Thiago Torres, Luciana Gambardella, Cedric Laueuenan, Caroline Reeb, Stephanie Caruso, Yazdan Yazdanpanah, John Brooks, Maria Paula Gomes Mourão, Constance Delaugerre, Jorge Andrade Pinto, Lisette Molins, Miguel Ekkelenkamp, Kristina Brooks, Esaú Custódio João, Jonathan Berardi, Valdiléa G. Veloso, Cecilie Moe, Pedro Enrique Cahn, Thomas R. Fleming, Emily Blum, Ines Aristegui
article en

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.

EClinicalMedicineVol. 93
Délégation Paris 5 (FR), Oslo University Hospital (NO), Harvard University (US), Inserm (FR), University of Basel (CH), University of Washington (US), Université Paris Cité (FR), University Hospital of Basel (CH), University of Bristol (GB), Sorbonne Paris Cité (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Bichat-Claude-Bernard (FR), Medical University of Vienna (AT)
Partnerships for the goals
Openalex Percentile: Top 46%
Ethics in Clinical Research
DOIOpen Access PDFOpenAlex
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