{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:07:51Z","timestamp":1778728071660,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is the third most common inherited monogenic kidney disorder. Mutations in\n                    <jats:italic>UMOD<\/jats:italic>\n                    and\n                    <jats:italic>MUC1<\/jats:italic>\n                    account for most cases, with the disease characterized by progressive eGFR decline leading to kidney failure. No disease\u2010modifying therapies exist, and transplantation is the only current option. Designing trials for ADTKD is hampered by small patient numbers, variable progression rates, and uncertainty around optimal endpoints. Building on natural history data from Wake Forest School of Medicine, nonlinear mixed\u2010effects models were developed to describe eGFR decline in\n                    <jats:italic>UMOD<\/jats:italic>\n                    and\n                    <jats:italic>MUC1<\/jats:italic>\n                    variants. These models formed the foundation for a web\u2010based clinical trial simulation (CTS) tool (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/app.cop.ufl.edu\/adtkd\/\">https:\/\/app.cop.ufl.edu\/adtkd\/<\/jats:ext-link>\n                    ) built in R Shiny. The tool allows users to define trial populations, configure design parameters, and estimate statistical power by simulating placebo vs. assumed treatment arms. Drug effects were modeled as percentage changes in key parameters of the developed disease progression models describing individual\u2010level eGFR trajectory over age: DPT\n                    <jats:sub>50<\/jats:sub>\n                    (age at which eGFR is half of its maximum decline),  and  (steepness before and after DPT\n                    <jats:sub>50<\/jats:sub>\n                    ). Both slope\u2010based eGFR change and end\u2010of\u2010trial eGFR measures functioned as effective surrogate endpoints. Herein, we present the model\u2010based CTS tool developed for ADTKD and demonstrate its use in designing and evaluating clinical trial scenarios, illustrated by two representative case studies. The CTS tool provides a pragmatic framework for optimizing ADTKD trial design. By enabling scenario testing and highlighting genotype\u2010specific considerations, it supports efficient, cost\u2010effective planning and represents an example of model\u2010informed drug development in rare kidney diseases.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70258","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:00:17Z","timestamp":1777608017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autosomal Dominant Tubulointerstitial Kidney Disease Clinical Trial Simulator: Case Reports of Model\u2010Informed Drug Development"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0623-5896","authenticated-orcid":false,"given":"Shyam S.","family":"Ramesh","sequence":"first","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-5851","authenticated-orcid":false,"given":"Mark","family":"Rogge","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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0459-8574","authenticated-orcid":false,"given":"Jongjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"},{"name":"Department of Statistics and Data Science University of Central Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-7479","authenticated-orcid":false,"given":"Sanghoon","family":"Kang","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-0949","authenticated-orcid":false,"given":"Kendrah","family":"Kidd","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne","family":"Williams","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Roignot","sequence":"additional","affiliation":[{"name":"Sail Bio, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Blakeslee","sequence":"additional","affiliation":[{"name":"Sail Bio, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Bleyer","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine  Winston\u2010Salem North Carolina 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"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882\u2010018\u20101107\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1806891"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.04.038"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.06380613"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2018.03.019"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000092147.83480.B5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab268"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018030245"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018020180"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3228"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010025\u201009989\u20100"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010150\u20109\u2010200905050\u201000006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102953"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v074.i11"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2976"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13246"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210639"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70258","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70258","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T02:17:43Z","timestamp":1778725063000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/psp4.70258"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70258","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"2025-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70258"}}