{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T11:39:08Z","timestamp":1763811548545,"version":"3.45.0"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Duchenne muscular dystrophy (DMD), a rare pediatric disease, presents numerous challenges when designing clinical trials, mainly due to the scarcity of available trial participants and the heterogeneity of disease progression. A quantitative clinical trial simulator (CTS) has been developed based on previously published five disease progression models describing each of the longitudinal changes in the velocity at which individuals can complete specified timed functional tests, frequently used as clinical trial efficacy endpoints (supine\u2010stand, 4\u2010stair climb, and 10\u2009m walk\/run test or 30\u2010foot walk\/run test), as well as each of the longitudinal changes in forced vital capacity and North Star Ambulatory Assessment total score. The model\u2010based CTS allows researchers to optimize the selection of numerous trial parameters for designing trials for the five functional measures commonly used as endpoints in DMD clinical trials. This case report serves as a demonstration of the tool's functionality while providing an easy\u2010to\u2010follow guide for users to reference when preparing simulations of their own design. Two case studies, using input selection based on previous DMD clinical trials, provide realistic examples of how the tool can help optimize clinical trial design without the risk of decreasing statistical significance. This optimization allows researchers to mitigate the risk of designing trials that may be longer, larger, or more inclusive\/exclusive than necessary.<\/jats:p>","DOI":"10.1002\/psp4.13281","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T03:45:08Z","timestamp":1732679108000},"page":"1787-1796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A computational tool to optimize clinical trial parameter selection in Duchenne muscular dystrophy: A practical guide and case studies"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4452-5841","authenticated-orcid":false,"given":"Jordan","family":"Wilk","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"},{"name":"Department of Mathematics, College of Sciences University of Central Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-0961","authenticated-orcid":false,"given":"Varun","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Pauley","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Corey","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela J.","family":"Conrado","sequence":"additional","affiliation":[{"name":"e\u2010Quantify LLC  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Lingineni","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceutical Corporation  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1588-9167","authenticated-orcid":false,"given":"Juan Francisco","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"},{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-8811","authenticated-orcid":false,"given":"Deok Yong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Cui","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-2041","authenticated-orcid":false,"given":"Jackson","family":"Burton","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-9679","authenticated-orcid":false,"given":"Jane","family":"Larkindale","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Collin","family":"Hovinga","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3272-8148","authenticated-orcid":false,"given":"Terina","family":"Martinez","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Romero","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-4972","authenticated-orcid":false,"given":"Ramona","family":"Belfiore\u2010Oshan","sequence":"additional","affiliation":[{"name":"Critical Path Institute (C\u2010Path)  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-0735","authenticated-orcid":false,"given":"Sarah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Duchenne Regulatory Science Consortium (D\u2010RSC) and the CINRG DNHS investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0631-3"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2013.746939"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(09)70271-6"},{"key":"e_1_2_13_5_1","unstructured":"https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010nonsteroidal\u2010treatment\u2010duchenne\u2010muscular\u2010dystrophy."},{"key":"e_1_2_13_6_1","unstructured":"DMD Clinical Trial Simulation (CTS) Tool. Critical Path Institute.https:\/\/c\u2010path.org\/program\/duchenne\u2010regulatory\u2010science\u2010consortium\/#dmd\u2010clinical\u2010tril\u2010simulation\u2010cts\u2010tool."},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12753"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-019-09642-7"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13246"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13021"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-024-09910-1"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13193"},{"key":"e_1_2_13_13_1","unstructured":"A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD) ClinicalTrials.govIdentifier: NCT03439670"},{"key":"e_1_2_13_14_1","unstructured":"A Study to Assess Safety\/Tolerability pk Effects on Histology Clinical Parameters of Givinostat in Children With DMD ClinicalTrials.govID NCT01761292."},{"key":"e_1_2_13_15_1","unstructured":"A 2\u2010part Phase 2 Study of Safety Pharmacokinetics and Biomarkers in Children With Duchenne Muscular Dystrophy Including a Randomized Double\u2010Blind Placebo\u2010Controlled Part A Followed by an Open\u2010Label Part B NCT05540860."},{"key":"e_1_2_13_16_1","unstructured":"Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non\u2010ambulatory Duchenne Muscular Dystrophy (DMD) (LELANTOS\u20101) ClinicalTrials.govID NCT04371666."},{"key":"e_1_2_13_17_1","unstructured":"Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy (PolarisDMD) ClinicalTrials.govID NCT03703882."},{"key":"e_1_2_13_18_1","unstructured":"Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy ClinicalTrials.govIdentifier: NCT02851797."},{"key":"e_1_2_13_19_1","unstructured":"Clinical Trial to Evaluate the Efficacy Safety and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy ClinicalTrials.govIdentifier: NCT03039686."}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T03:41:25Z","timestamp":1763782885000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/psp4.13281"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13281","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"type":"print","value":"2163-8306"},{"type":"electronic","value":"2163-8306"}],"subject":[],"published":{"date-parts":[[2024,11,27]]},"assertion":[{"value":"2024-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}