{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:11:28Z","timestamp":1760573488464,"version":"build-2065373602"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Phase 2 trials have historically focused on characterizing the dose\u2010exposure\u2010response relationship in relatively homogeneous patient populations before proceeding to confirmatory trials. However, with the rise of multi\u2010regional Phase 2 trials, it is important to strike a balance between this goal and the requirement to make sure that the optimal doses are chosen for patients from various geographic areas. This study uses a dose\u2010ranging trial for an anti\u2010psoriatic drug, featuring a typical design with a total sample size of <jats:italic>N<\/jats:italic>\u2009=\u2009175, to highlight key considerations regarding sample size in multi\u2010regional exploratory studies. The allocation of sample size to a region of interest (Region X) was evaluated using both a conventional statistical approach and a pharmacometric model\u2010based (PMx) approach, predicated on the assumption of a minimum treatment improvement in Region X. Further evaluation was performed to assess the probability of reaching reliable conclusions regarding clinically relevant inter\u2010regional differences in treatment response. The statistical approach, relying solely on end\u2010of\u2010trial observations from a single dose group, exhibited a maximum power of less than 40% in detecting treatment differences across regions when Region X accounts for 50% of the total sample size. In contrast, the PMx approach, employing data from multiple dose groups across trial duration, demonstrated that 26% of the total sample size yielded over 80% power to identify the inter\u2010regional difference. The PMx approach has also been shown to offer a more efficient characterization of the clinical relevance of inter\u2010regional differences, and has potential to improve decision\u2010making in development progression by integrating prior knowledge.<\/jats:p>","DOI":"10.1002\/psp4.70090","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T06:39:06Z","timestamp":1754116746000},"page":"1673-1681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacometric Model\u2010Based Sample Size Allocation for a Region of Interest in a Multi\u2010Regional Phase 2 Trial: A Case Study of an Anti\u2010Psoriatic Drug"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2033-0895","authenticated-orcid":false,"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[{"name":"GSK  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-4899","authenticated-orcid":false,"given":"Yubo","family":"Xiao","sequence":"additional","affiliation":[{"name":"GSK  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9017-9400","authenticated-orcid":false,"given":"Junyi","family":"Wu","sequence":"additional","affiliation":[{"name":"GSK  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5657-8584","authenticated-orcid":false,"given":"Scott","family":"Marshall","sequence":"additional","affiliation":[{"name":"GSK  Stevenage Hertfordshire UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5750-1728","authenticated-orcid":false,"given":"Xuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"GSK  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774518813573"},{"key":"e_1_2_9_3_1","unstructured":"International council for harmonisation of technical requirements for pharmaceuticals for human use (ICH) E17 General Principles for Planning and Design of Multiregional Clinical Trials https:\/\/www.fda.gov\/media\/99974\/download."},{"key":"e_1_2_9_4_1","unstructured":"CDE International Multi\u2010Center Clinical Trial Guidelines (Trial) https:\/\/www.cde.org.cn\/zdyz\/domesticinfopage?zdyzIdCODE=1af85e6ee03eddc643c00c9a3b261e3d."},{"key":"e_1_2_9_5_1","unstructured":"CDE Technical Guideline for Acceptance of Overseas Clinical Trial Data for Drugs https:\/\/www.cde.org.cn\/zdyz\/domesticinfopage?zdyzIdCODE=fd093b6ea252c55ff5cc7da15071f0b6."},{"key":"e_1_2_9_6_1","unstructured":"Ministry of Health Labour and Welfare of Japan (MHLW) Basic Principles on Global Clinical Trials http:\/\/www.pmda.go.jp\/files\/000153265.pdf."},{"key":"e_1_2_9_7_1","unstructured":"CDE Guidelines for Benefit\u2010Risk Assessment Based on Multi\u2010Regional Clinical Trial Data in the Global Simultaneous Development of New Drugs (Draft for Comments) https:\/\/www.cde.org.cn\/main\/news\/viewInfoCommon\/196f2d48912515aa6ca3175f545ebee8."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543400902963185"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2012.24"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.103"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.163"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000745\u20105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/13596535231151626"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2003.09.014"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041\u2010210X.2010.00014.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010012\u20109327\u20108"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010016\u20100144\u20100"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1214\/09\u2010BA431"}],"container-title":["CPT: Pharmacometrics &amp; 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