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This study suggests sample enrichment approaches to facilitate preventive trials to delay disease onset in individuals with the dominant gene for Huntington disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using published onset prediction indexes, we conducted the receiver operating curve analysis for diagnosis within a 3\u2010year clinical trial time frame. We determined optimal cut points on the indexes for participant recruitment and then conducted sample size and power calculations to detect varying effect sizes for treatment efficacy in reducing 3\u2010year rates of disease onset (or diagnosis).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Area under the curve for 3 onset prediction indexes all demonstrated excellent value in sample enrichment methodology, with the best\u2010performing index being the multivariate risk score (MRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study showed that conducting an intervention trial in premanifest and prodromal individuals with the gene expansion for Huntington disease is highly feasible using sample enrichment recruitment methods. Ongoing natural history studies are highly likely to indicate additional markers of disease prior to diagnosis. Statistical modeling of identified markers can facilitate participant enrichment to increase the likelihood of detecting a difference between treatment arms in a cost\u2010effective and efficient manner. Such variations may expedite translation of emerging therapies to persons in an earlier phase of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>PREDICT\u2010HD is registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>, number NCT00051324. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27595","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T22:12:42Z","timestamp":1547503962000},"page":"274-280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sample enrichment for clinical trials to show delay of onset in huntington disease"],"prefix":"10.1002","volume":"34","author":[{"given":"Jane S.","family":"Paulsen","sequence":"first","affiliation":[{"name":"Departments 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