Lancet neurology
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The current research paradigm for Huntington's disease is based on participants with overt clinical phenotypes and does not address its pathophysiology nor the biomarker changes that can precede by decades the functional decline. We have generated a new research framework to standardise clinical research and enable interventional studies earlier in the disease course. The Huntington's Disease Integrated Staging System (HD-ISS) comprises a biological research definition and evidence-based staging centred on biological, clinical, and functional assessments. ⋯ Individuals can be precisely classified into stages based on thresholds of stage-specific landmark assessments. We also demonstrated the internal validity of this system. The adoption of the HD-ISS could facilitate the design of clinical trials targeting populations before clinical motor diagnosis and enable data standardisation across ongoing and future studies.