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Predictive models of ambulatory progression could enhance understanding of gait\/balance disturbances and aid in trial design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To predict trajectories of ambulatory abilities from baseline clinical data in early PD, relate trajectories to clinical milestones, compare biomarkers, and evaluate trajectories for enrichment of clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from two multicenter, longitudinal, observational studies were used for model training (Tracking Parkinson's, n\u2009=\u20091598) and external testing (Parkinson's Progression Markers Initiative, n\u2009=\u2009407). Models were trained and validated to predict individuals as having a \u201cProgressive\u201d or \u201cStable\u201d trajectory based on changes of ambulatory capacity scores from the Movement Disorders Society Unified Parkinson's Disease Rating Scale parts II and III. Survival analyses compared time\u2010to\u2010clinical milestones and trial outcomes between predicted trajectories.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>On external evaluation, a support vector machine model predicted Progressive trajectories using baseline clinical data with an accuracy, weighted\u2010F1 (proportionally weighted harmonic mean of precision and sensitivity), and sensitivity\/specificity of 0.735, 0.799, and 0.688\/0.739, respectively. Over 4\u2009years, the predicted Progressive trajectory was more likely to experience impaired balance, loss of independence, impaired function and cognition. Baseline dopamine transporter imaging and select biomarkers of neurodegeneration were significantly different between predicted trajectory groups. For an 18\u2010month, randomized (1:1) clinical trial, sample size savings up to 30% were possible when enrollment was enriched for the Progressive trajectory versus no enrichment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It is possible to predict ambulatory abilities from clinical data that are associated with meaningful outcomes in people with early PD. \u00a9 2023 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29519","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T12:18:47Z","timestamp":1687781927000},"page":"1774-1785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-9513","authenticated-orcid":false,"given":"Charles S.","family":"Venuto","sequence":"first","affiliation":[{"name":"Center for Health + Technology University of Rochester  Rochester New York USA"},{"name":"Department of Neurology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Health + Technology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konnor","family":"Herbst","sequence":"additional","affiliation":[{"name":"Center for Health + Technology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zielinski","sequence":"additional","affiliation":[{"name":"Center for Health + Technology University of Rochester  Rochester New York USA"},{"name":"Department of Biostatistics Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman C.W.","family":"Yung","sequence":"additional","affiliation":[{"name":"Center for Health + Technology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G.","family":"Grosset","sequence":"additional","affiliation":[{"name":"School of Neuroscience and Psychology University of Glasgow  Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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