A core outcome set for pharmacological treatments in hospitalised patients with acute viral respiratory infections (COSAVRI)

Background
Acute viral respiratory infections (AVRIs) rank among the most common causes of hospitalisation worldwide, imposing significant healthcare burdens and driving the development of various pharmacological treatments. However, inconsistent outcome reporting across clinical trials limits evidence synthesis and its translation into clinical practice. A core outcome set (COS) for pharmacological treatments in hospitalised adults with AVRIs is essential to standardise trial outcomes and improve research comparability.

Objective
To develop a consensus on an internationally agreed COS for pharmacological treatments in hospitalised adults >18 years with acute viral respiratory infections (COSAVRI) through stakeholder agreement.

Methods
This protocol follows a four-stage development process in accordance with the Core Outcome Set Handbook guidelines. Stage 1 comprises a rapid scoping review of randomised controlled trials (2015-2025) to systematically catalogue patient-relevant outcomes reported in pharmacological AVRI treatment studies. Semi-automated screening and data extraction will employ machine learning and large language models, with human verification. Stage 2 involves an online Real-Time Delphi survey with international stakeholders, including healthcare professionals, researchers, patients/caregivers, and policymakers, to prioritise identified outcomes using a 9-point scale. Stage 3 consists of structured online consensus meetings utilising anonymous electronic voting to finalise the COS. Stage 4 focuses on dissemination and implementation through academic publications, conferences, and stakeholder engagement.

Expected outcomes
COSAVRI will provide a standardised minimum set of outcomes for measuring and reporting in future pharmacological trials involving hospitalised adults with AVRIs. This initiative will enhance evidence synthesis, reduce research waste, support regulatory decision-making, and improve pandemic preparedness by facilitating the rapid deployment of harmonised outcomes in trial protocols.

Potentially relevant COS
Our COMET search identified respiratory core outcome sets that were COVID-19 specific (treatment, prevention, post-COVID), plus sets for COPD exacerbations, bronchiolitis, and acute respiratory failure. While COVID-19 treatment sets offer relevant endpoints (mortality, ventilation), all existing sets are limited by being pathogen-specific (eg COVID only), age-specific (eg paediatric bronchiolitis), condition-specific (eg COPD, Asthma), or focused on prevention/rehabilitation rather than acute treatment. None address multiple respiratory viruses or include cross-pathogen virological and antiviral safety outcomes. COSAVRI will provide the first pan-viral, treatment-focused outcome set for adult inpatient trials, enabling evidence synthesis across pathogens and supporting rapid trial deployment in future pandemics.

Contributors

Declan Devane (PI)
Center for Health Research Methods, School of Nursing and Midwifery, University of Galway, Galway, Ireland
Health Research Board–Trials Methodology Research Network (HRB-TMRN), University of Galway, Galway, Ireland
Evidence Synthesis Ireland and Cochrane Ireland, University of Galway, Galway, Ireland

Matthias Briel
CLEAR Methods Center, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland

Sanjay Bhagani
Department of Infectious Diseases and HIV Medicine, Royal Free London NHS Trust and Division of Infection and Immunity
University College London, United Kingdom

Nadine Boesten
European Patients Forum, Brussels, Belgium

Stephanie Buchholz
Public Health Threats Department, European Medicines Agency, Amsterdam, Netherlands; and, Division 32, "Infectiology/Dermatology/Allergology," Federal Institute for Drugs and Medical Devices, Germany.

Estefania Callejas De Luca
European Patients Forum, Brussels, Belgium

Jeremie Guedj
Université Paris Cité, INSERM, IAME, F-75018 Paris, France

Anastasia Koryakina
EPPI Centre, Social Research Institute
University College London, United Kingdom

Kavita Kothari
Consultant to Evidence Synthesis Ireland and Cochrane Ireland, University of Galway, Galway, Ireland

Karine Lacombe
Sorbonne Université, INSERM IPLESP, Infectious Diseases Department, St Antoine Hospital, APHP, Paris, France

Patrick W Mallon
Centre for Experimental Pathogen Host Research, School of Medicine, University College Dublin, Ireland

Clément R. Massonnaud
Université Paris Cité, Inserm, IAME, Département d’Épidémiologie, Biostatistique et Recherche Clinique, Hôpital Bichat, APHP, Paris France

Joanne O'Dwyer
Discipline of Pharmacy, School of Pharmacy and Medical Sciences, University of Galway, Galway, Ireland

Inge Christoffer Olsen
Dept. of Research Support for Clinical Trials, Oslo University Hospital, Norway.

KM Saif-Ur-Rahman
Evidence Synthesis Ireland and Cochrane Ireland, University of Galway, Galway, Ireland
Center for Health Research Methods, School of Nursing and Midwifery
University of Galway, Galway, Ireland

Johannes M. Schwenke
CLEAR Methods Center, Division of Clinical Epidemiology, Department of Clinical Research
University Hospital Basel, University of Basel, Basel, Switzerland

James Thomas
EPPI Centre, Social Research Institute
University College London, United Kingdom

Yazdan Yazdanpanah
ANRS Emerging infectious disease, Inserm, Paris, France

Lina Zgaga
Department of Public Health and Primary Care, Institute of Population Health
Trinity College Dublin, University of Dublin, Ireland.

Julia Louw
Center for Health Research Methods, School of Nursing and Midwifery, University of Galway, Galway, Ireland
Health Research Board–Trials Methodology Research Network (HRB-TMRN), University of Galway, Galway, Ireland

Further Study Information

Current Stage: Ongoing
Date: January 2025 - January 2027
Funding source(s): This study is funded by the PROACT EU-RESPONSE project, which is supported by the EU Horizon Europe programme under grant agreement No 101156304. The findings and conclusions in this document are those of the authors and do not necessarily represent the views of the PROACT EU-RESPONSE project consortium. The funder did not participate in the design, analysis, or decision to publish this study.


Health Area

Disease Category: Infectious disease, Lungs & airways

Disease Name: Acute viral respiratory infections

Target Population

Age Range: 18 - 120

Sex: Either

Nature of Intervention: Drug

Stakeholders Involved

- Clinical experts
- Consumers (caregivers)
- Consumers (patients)
- Epidemiologists
- Methodologists
- Patient/ support group representatives
- Policy makers
- Regulatory agency representatives
- Researchers
- Service providers
- Service users
- Statisticians

Study Type

- COS for clinical trials or clinical research
- COS for practice

Method(s)

- Consensus meeting
- Delphi process
- Survey
- Systematic review

This protocol follows a four-stage development process in accordance with the Core Outcome Set Handbook guidelines. Stage 1 comprises a rapid scoping review of randomised controlled trials (2015-2025) to systematically catalogue patient-relevant outcomes reported in pharmacological AVRI treatment studies. Semi-automated screening and data extraction will employ machine learning and large language models, with human verification. Stage 2 involves an online Real-Time Delphi survey with international stakeholders, including healthcare professionals, researchers, patients/caregivers, and policymakers, to prioritise identified outcomes using a 9-point scale. Stage 3 consists of structured online consensus meetings utilising anonymous electronic voting to finalise the COS. Stage 4 focuses on dissemination and implementation through academic publications, conferences, and stakeholder engagement.

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