Core outcome measurement set for clinical trials in dengue: an international Delphi consensus study (DEN-CORE).
| Title: | Core outcome measurement set for clinical trials in dengue: an international Delphi consensus study (DEN-CORE). |
|---|---|
| Authors: | Yacoub S; 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.; Demidova A; Independent researcher, Limassol, Cyprus.; Chan XHS; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Ajam A; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.; Baimukhambetova D; 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.; Horn A; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.; Kakotkina E; Independent researcher, Hsinchu, Taiwan.; Kosenko M; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.; Mursalova A; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia.; Van Nuil JI; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Phuong CL; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Xiao L; 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.; Adhikari S; Oxford University Clinical Research Unit Nepal, Lalitpur, Nepal.; Alzate Alvarez JD; The Chang Laboratory, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.; Anderson KB; Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY, USA.; Avirutnan P; 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.; Buchholz S; European Medicines Agency, Amsterdam, Netherlands; Federal Institute for Drugs and Medical Devices, Bonn, Germany.; Chandra R; Novartis Pharmaceuticals, East Hanover, NJ, USA.; Chang AY; Department of Medicine, George Washington University, Washington, DC, USA.; Quang Chanh H; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Consuegra Rodríguez MP; Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.; Daniel V; Drugs for Neglected Diseases Initiative South-East Asia, Kuala Lumpur, Malaysia.; Diaz JV; World Health Organization, Geneva, Switzerland.; Figueiredo-Mello C; Department of Medicine, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.; Gelvez-Ramírez RM; Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.; Huyen TB; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Kestelyn E; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Lam PK; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.; Leopold SJ; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.; Li R; China Novartis Institute of Biomedical Research, Shanghai, China.; Luu T; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Lye DCB; 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.; McBride A; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Meyer-Andrieux I; Novartis Global Health, Basel, Switzerland.; Moorman NJ; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Nguyen NM; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Omar SFS; Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; CERIA, Centre of Excellence for Research in Infectious Diseases & AIDS, Universiti Malaya, Kuala Lumpur, Malaysia.; Ong HC; Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; CERIA, Centre of Excellence for Research in Infectious Diseases & AIDS, Universiti Malaya, Kuala Lumpur, Malaysia.; Ooi EE; Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore.; Pazukhina E; Wolfson Institute of Population Health, Queen Mary University of London, London, UK.; Pett SL; MRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.; Porto DB; Faculty of Medicine, Department of Clinical Medicine, Federal University of Ceará, Ceará, Brazil.; Rajahram GS; Department of Medicine, Queen Elizabeth Hospital II, Ministry of Health Malaysia, Kota Kinabalu, Malaysia.; Rogers M; Novartis Global Health, Basel, Switzerland.; Rojas E; Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.; Rosen J; Rapidly Emerging Antiviral Drug Discovery Initiative, Research Triangle Park, NC, USA.; Rylance J; Health Emergencies Program, World Health Organization, Geneva, Switzerland.; Schilling WHK; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Siqueira AM; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil; Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.; Sjö P; Drugs for Neglected Diseases initiative, Geneva, Switzerland.; Sucerquia-Hernandez A; Department of Medicine, George Washington University, Washington, DC, USA.; Tam DTH; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.; Teixeira MM; Department of Biochemistry and Immunology and Center for Advanced and Innovative Therapies, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Tietz A; Novartis Global Health, Basel, Switzerland.; Trieu HT; Paediatric Intensive Care Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.; Unsworth A; Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology-Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.; Villar L; Centro de Atención y Diagnóstico de Enfermedades Infecciosas SAS, Grupo INFOVIDA, Bucaramanga, Colombia.; Waickman AT; Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY, USA; Institute for Global Health and Translational Sciences, State University of New York Upstate Medical University, Syracuse, NY, USA.; Watson JA; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK; Infectious Diseases Data Observatory, Oxford, UK.; Wills BA; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Chia PY; National Centre for Infectious Diseases, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.; Brasil P; Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.; Jaenisch T; Heidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany; Center for Global Health, Colorado School of Public Health, Aurora, CO, USA.; Lum L; Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.; Malavige GN; Department of Immunology and Molecular Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Gangodawila, Sri Lanka.; McGloughlin S; Department of Intensive Care Alfred Health, Monash University School of Public Health, Melbourne, VIC, Australia.; Tirupakuzhi Vijayaraghavan BK; Department of Critical Care Medicine, Apollo Hospitals, Chennai, India; The George Institute for Global Health, New Delhi, India; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.; Merson L; International Severe Acute Respiratory and Emerging Infection Consortium, Pandemic Sciences Institute, University of Oxford, Oxford, UK; Institut Pasteur de Dakar, Dakar, Senegal.; Munblit D; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia; Care for Long Term Conditions Division, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK. Electronic address: daniel.munblit@kcl.ac.uk. |
| Corporate Authors: | DEN-CORE Study Group |
| Source: | The Lancet. Infectious diseases [Lancet Infect Dis] 2026 Apr; Vol. 26 (4), pp. e231-e244. Date of Electronic Publication: 2025 Oct 07. |
| Publication Type: | Journal Article; Systematic Review; Review |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-4457 (Electronic) Linking ISSN: 14733099 NLM ISO Abbreviation: Lancet Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001- |
| MeSH Terms: | Dengue*/therapy ; Clinical Trials as Topic* ; Outcome Assessment, Health Care*; Humans ; Delphi Technique ; Consensus |
| 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.; (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| Competing Interests: | Declaration of interests SY serves on the scientific committee for the Takeda dengue vaccine programme; has participated in an advisory board for Novartis; and is chair of the data and safety monitoring board for a phase 2 antiviral trial. JIVN reports receiving grants from the Wellcome Trust, University of Oxford, and Agence Nationale de Recherche sur le Sida et les Hépatites Virales. KBA reports funding from the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases [NIAID], Fogarty) and the Wellcome Trust; travel support from the PanDengue Summit organisers for a 2025 plenary address in Colombia; and is a member of the HealtheConnections advisory board. PA reports receiving the Chair Professor Research Grant (P16–50392) and cofunding research grants ([IO]R016536001 and P-20–52570) from the National Science and Technology Development Agency and the Faculty of Medicine Siriraj Hospital, Mahidol University; has received a joint MRC-NSTDA-TRF research grant ((IO)R015936005) and support from the RED programme at the Faculty of Medicine Siriraj Hospital; and has served on advisory boards for the PLATCOV and AD ASTRA trials. EEO reports receiving National Medical Research Council (MRC) grants for studies on vaccines (MOH-000505–04), flaviviral host response (MOH-000601–00; NRF-CRP25–2020–0003), and dengue (MOH-000271–00); has served on advisory boards for Takeda, Sanofi Pasteur, Johnson & Johnson, Novartis, and Arcturus Therapeutics; and has served as DSMB Chair for Johnson & Johnson. SLP holds research grants from the University of Minnesota, EDCTP-2, EDCTP-3, National Institute for Health and Care Research (NIHR), Gilead Sciences, ViiV Healthcare, MRC, and Janssen-Cilag; serves as a DSMB member for the TIPAL trial (NIHR funded) and the IMPEDE-PKD trial (NIHR funded). GSR reports grants from the National Institutes of Health and the Malaysian Ministry of Health; has served as a speaker at ICTMM 2024, ESCMID Global 2025, and the 7th Asia Dengue Summit, where he was also a committee member; and is a member of the Malaysian Medical Council Specialty Education Committee. AT is a shareholder of Novartis. CPY reports an honorarium from Takeda (to institution); has received grant funding to institution from Ministry of Health, Singapore, and sponsored trial funding to institution from AstraZeneca and Novartis. NM served in advisory roles on dengue for Johnson & Johnson, Novartis, and Abbott. BKTV reports receiving funding for a pilot trial of corticosteroids in patients hospitalied with dengue from the University of Toronto India Foundation. DM reports receiving grants from the Bill & Melinda Gates Foundation [INV-063472] and the Academy of Medical Sciences Networking Grant Scheme (NGR1\1953); support for attending meetings organised by the International Severe Acute Respiratory and emerging Infection Consortium and WHO. All other authors declare no competing interests. |
| Grant Information: | 001 International WHO_ World Health Organization |
| Contributed Indexing: | Investigator: S Ab Wahab; NK Adhikari; MJ Ahmed; E Arguni; D Aryal; A Bakri; L Sl Bastos; S Bhusal; L Blanco; J Caoili; JC Celis-Salinas; S Chaiwang; A Chesnokov; R Claure-Del Granado; YV Cruz; A Dahal; R Dewi; K Fareed; L Felipe Reyes; M Hashmi; TT Jayadas; M Joshi; MV Karunananda; LC Katzelnick; M Kevin; SW Lee; YS Leo; N M; J Marshall; MZ Mazlan; A Mustafa; DM Needham; TVT Nguyen; H Nguyen; DTP Nguyen; P Olliaro; AP Pasaribu; BJC Perera; AV Potey; A Poudel; K Puspatriani; M Rahardjani; G Rasheed; AJ Rodriguez-Morales; L Rose; N Salahuddin; NE Santiago; WH Self; M Shakya; HT Siddiqui; TL Thein; LC Thwaites; S Tripathy; HR van Doorn; D Vijayan; T Vo; S Yatiwelle; Elisa |
| Entry Date(s): | Date Created: 20251010 Date Completed: 20260327 Latest Revision: 20260328 |
| Update Code: | 20260329 |
| DOI: | 10.1016/S1473-3099(25)00500-6 |
| PMID: | 41072450 |
| Database: | MEDLINE |
Journal Article; Systematic Review; Review