Global Consensus Sets New Standards for Measuring Outcomes in Dengue Clinical Trials

As dengue continues its alarming rise across the globe, researchers are uniting around a critical step toward more reliable and comparable clinical trials: standardizing what outcomes should be measured and how. An international consortium of researchers, clinicians, and patients has developed the first Core Outcome Measurement Set (COMS) for dengue clinical trials—a landmark achievement designed to harmonize study endpoints and elevate the quality of dengue research worldwide.

The initiative, known as DEN-CORE, addressed one of the major challenges facing dengue research today: the lack of uniformity in trial outcomes. Despite an expanding body of research and increasing urgency driven by climate change, urbanization, and the widening range of Aedes mosquito vectors, the field has been hindered by fragmented reporting and outcome definitions that make comparing and synthesizing findings difficult.

To resolve this, the DEN-CORE team undertook a rigorous, two-phase consensus process, guided by international standards including the Core Outcome Measures in Effectiveness Trials (COMET) initiative and Core Outcome Set–Standards for Development (COS-STAD) guidelines.

Phase One focused on developing a Core Outcome Set (COS)—the “what” to measure. The process began with a systematic review of existing clinical trials to catalogue current outcome reporting practices. To ensure that the COS was both clinically meaningful and patient-centered, the team incorporated qualitative interviews with people who had lived through dengue infection. These insights were integrated with expert input from a global steering committee and management group.

The findings fed into a structured Delphi process, a method widely used for building expert consensus. Through two survey rounds and online consensus meetings, stakeholders refined and finalized core outcomes for both hospitalized and early-stage dengue patients. Informed by critical care specialists, the team also provided guidance for studies involving patients in ICUs or high-dependency settings, aligning these with existing ICU-specific core outcome sets.

Phase Two moved from the “what” to the “how”: defining the most appropriate measurement instruments for each core outcome. This step involved a targeted review of existing tools, followed by a hybrid international workshop that brought together a diverse group of participants to reach final agreement on the COMS.

The resulting Core Outcome Measurement Set for Hospitalised Dengue includes seven priority outcomes. The Early-Stage Dengue COMS builds on this with four additional outcomes, reflecting the distinct needs of ambulatory or less severe cases. For trials in critical care settings, the use of established ICU-specific outcome sets was recommended. In addition, the team developed unified definitions for nine clinician-reported outcomes—an important step in reducing interpretative variation between trials.

By anchoring future research in a standardized framework, the DEN-CORE COMS is poised to transform how evidence is generated, compared, and applied in dengue research. Researchers designing clinical trials now have a validated roadmap to follow, ensuring that their results will be both relevant and interoperable with those from other studies. This is particularly crucial in the context of global health, where interventions may span diverse geographic, clinical, and healthcare settings.

The adoption of the DEN-CORE COMS will also support systematic reviews, meta-analyses, and evidence-based policymaking, helping public health authorities and clinicians make better-informed decisions about the management and prevention of dengue. In an era of growing vector-borne disease burden, such harmonization is not just desirable—it is essential.

With dengue cases surging and climate-related factors accelerating its spread, the DEN-CORE initiative offers a timely and practical tool for improving the rigor and impact of dengue clinical research. Its collaborative and inclusive methodology also provides a blueprint for future core outcome set development in other areas of infectious disease and global health.

As the world races to develop better diagnostics, treatments, and vaccines for dengue, the clarity brought by a globally endorsed outcome framework may prove just as vital as the interventions themselves.