Core outcome measurement set for clinical trials in dengue: an international Delphi consensus study (DEN-CORE)

Sophie Yacoub, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK. Electronic address: syacoub@oucru.org.
Anastasia Demidova, Independent researcher, Limassol, Cyprus.
Xin Hui Chan, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Ali Ajam, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.
Dina Baimukhambetova, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia; Medical University of Vienna, Vienna, Austria.
Andreij Horn, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.
Evgeniia Kakotkina, Independent researcher, Hsinchu, Taiwan.
Mark Kosenko, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.
Aigun Mursalova, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.
Jennifer Ilo Van Nuil, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Chi Le Phuong, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
Lin Xiao, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia; Obstetrics and Gynecology Department, Princess Marina Hospital, Gaborone, Botswana.
Sudeep Adhikari, Oxford University Clinical Research Unit Nepal, Lalitpur, Nepal.
Juan David Alzate Alvarez, The Chang Laboratory, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Kathryn B. Anderson, Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY, USA.
Panisadee Avirutnan, Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Stephanie Buchholz, European Medicines Agency, Amsterdam, Netherlands; Federal Institute for Drugs and Medical Devices, Bonn, Germany.
Richa Chandra, Novartis Pharmaceuticals, East Hanover, NJ, USA.
Aileen Y. Chang, Department of Medicine, George Washington University, Washington, DC, USA.
Ho Quang Chanh, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
Mónika Patricia Consuegra Rodríguez, Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.
Vanessa Daniel, Drugs for Neglected Diseases Initiative South-East Asia, Kuala Lumpur, Malaysia.
Janet V. Diaz, World Health Organization, Geneva, Switzerland.
Claudia Figueiredo-Mello, Department of Medicine, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.
Rosa Margarita Gelvez-Ramírez, Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.
Tran Bang Huyen, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
Evelyne Kestelyn, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Phung Khanh Lam, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
Stije J. Leopold, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
Ruobing Li, China Novartis Institute of Biomedical Research, Shanghai, China.
Tran Luu, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
David Chien Lye, National Centre for Infectious Diseases, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

Document Type

Journal Article

Publication Date

10-7-2025

Journal

The Lancet. Infectious diseases

DOI

10.1016/S1473-3099(25)00500-6

Abstract

Dengue, caused by any one of four distinct virus serotypes, is the most rapidly spreading mosquito-borne viral disease worldwide. It is a primary arboviral infection with increasing global incidence, driven by climate change, urbanisation, and the expanding range of Aedes mosquito vectors. Despite growing research interest, outcome and measurement instrument heterogeneity in dengue clinical trials remains high, limiting comparability and evidence synthesis. This project aimed to develop a globally relevant Core Outcome Measurement Set (COMS) for use in dengue clinical trials through international consensus. This consensus study followed core outcome measures in effectiveness trials and Core Outcome Set-Standards for Development (COS-STAD) guidelines and was conducted in two phases. Phase 1 focused on developing a Core Outcome Set (COS) through four steps: (1) a systematic literature review; (2) qualitative interviews with people with lived experience of dengue; (3) review by the management group and steering committee; (4) a two-round modified Delphi survey and structured online consensus meetings to finalise the COS for hospitalised and early stages of dengue disease. Input from critical care experts informed recommendations for the intensive care unit (ICU) and high dependency unit COS. Phase 2 consisted of a further two steps: (1) targeted review of outcome measurement instruments; and (2) a hybrid international consensus workshop to finalise the COMS. The agreed COMS for hospitalised dengue included seven outcomes; the early stage dengue COS included these outcomes plus four more. For critical care trials, use of existing ICU-specific COS was recommended. Unified definitions were developed for nine clinician-reported outcomes. The DEN-CORE COMS provides a consensus-based framework for harmonising outcome selection and measurement in dengue trials, improving comparability and supporting policy and clinical decision making.

Department

Microbiology, Immunology, and Tropical Medicine

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