{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:30:07Z","timestamp":1778567407011,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T00:00:00Z","timestamp":1589587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Development of effective therapeutics that slow Huntington's disease progression is a research priority that requires an understanding of natural disease progression. We applied a population\u2010modeling approach to describe the progression of 2 routinely used rating scales \u2014 the total motor score and the total functional capacity score. Models were fitted to data from research participants aged \u2265 18 years with Huntington's disease stage I or II at study entry (total functional capacity score \u2265 7), from a controlled clinical trial (CARE\u2010HD) and 2 observational studies (COHORT and Registry). A logistic model without shape factors was selected as the base model based on placebo data from CARE\u2010HD and validated using data from the CARE\u2010HD active\u2010treatment arms. Albeit with a smaller progression rate constant than was found in CARE\u2010HD, the proposed models provided reasonable predictions for both rating scales in the pooled data from COHORT and Registry and were considered suitable for use in clinical trial simulations. Results also showed that disease burden score (a product of age and expanded CAG length) is a significant covariate on both the progression rate constant and the baseline score in the total motor score model. These findings suggest that total motor score and total functional capacity progress fastest near their half\u2010maximal score, implying that the efficiency of clinical trials evaluating disease\u2010modifying therapeutics for Huntington's disease could be enhanced by enrolling patients with faster disease progression or evaluating treatment effect near their half\u2010maximal score, provided that the evaluated therapy is expected to be efficacious at this disease stage.<\/jats:p>","DOI":"10.1002\/jcph.1598","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T19:40:00Z","timestamp":1589658000000},"page":"1051-1060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Huntington's Disease Progression: A Population Modeling Approach to Characterization Using Clinical Rating Scales"],"prefix":"10.1002","volume":"60","author":[{"given":"Wan","family":"Sun","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology Takeda Pharmaceuticals Cambridge Massachusetts USA"},{"name":"Division of Pharmacometrics Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Pharmacometrics Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Warner","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas R.","family":"Langbehn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guenther","family":"Hochhaus","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Florida Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaning","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pharmacometrics Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,16]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"US Department of Health and Human Services & Food and Drug Administration.2008.Innovation or stagnation? Challenge and opportunity on the critical path to new medical products. March 2004.https:\/\/wayback.archive-it.org\/7993\/20180125032208\/https:\/\/www.fda.gov\/ScienceResearch\/SpecialTopics\/CriticalPathInitiative\/CriticalPathOpportunitiesReports\/ucm077262.htm. 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