{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:40:32Z","timestamp":1792068032103,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite the fact that modeling and simulation are now recognized as promising innovative methodologies, their use in the context of development of drugs for sickle cell disease and Thalassemia has not yet been reviewed. Considering the challenges of conducting clinical trials for hemoglobinopathies, our work aims at exploring the current status of use of modeling and simulation by drug developers and their endorsement by regulators, based on European Medicines Agency scientific advices given to industry by the Committee for Medicinal Products for Human Use from January 2000 to December 2024. The present study describes different aspects of how modeling and simulation methods have been used and assessed. Our results highlight the need for an openly accessible structured framework that details the standards\/criteria that make a method acceptable for regulators. The use of the ICH M15 credibility assessment framework is suggested for this purpose. Bearing in mind the question\u2010centric approach, a repository of drug development questions and associated methods and data was built from 45 and 31 scientific advices for sickle cell disease and Thalassemia, respectively. The classification of the questions, methods and data based on the question\u2010centric approach enabled modeling and simulation methods to be easily identified, objectively assessed and benchmarked against alternative methods used to address the same questions to evaluate their performance for characterizing benefit\/risk of the different drugs.<\/jats:p>","DOI":"10.1002\/psp4.70192","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:12:30Z","timestamp":1772957550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessment and Benchmarking of Model Informed Approaches in Drug Development for Hemoglobinopathies: A Review of Scientific Advices From January 2000 to December 2024"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1375-6058","authenticated-orcid":false,"given":"Grace Shalom","family":"Govere","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmacologie et toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS) University of Namur  Namur Belgium"},{"name":"Federal Agency for Medicines and Health Products (FAMHP)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-1804","authenticated-orcid":false,"given":"Jean\u2010Michel","family":"Dogn\u00e9","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmacologie et toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS) University of Namur  Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-8870","authenticated-orcid":false,"given":"Flora","family":"Musuamba","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmacologie et toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS) University of Namur  Namur Belgium"},{"name":"Federal Agency for Medicines and Health Products (FAMHP)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010023\u201004900\u2010w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107299\u20109_3"},{"key":"e_1_2_8_4_1","unstructured":"European Medicines Agency \u201cEMA\u2014Medicines\u2014Human Regulatory\u2014Sicke Cell Disease \u201d2025 accessed July 11 2025 https:\/\/www.ema.europa.eu\/en\/search?f%5B0%5D=ema_search_topics%3A61&landing_from=73303&search_api_fulltext=sickle%20cell%20disease&page=0."},{"key":"e_1_2_8_5_1","unstructured":"European Medicines Agency \u201cEMA\u2014Medicines\u2014Human Regulatory\u2014Thalassaemia \u201d2025 accessed July 11 2025 https:\/\/www.ema.europa.eu\/en\/search?landing_from=73303&search_api_fulltext=Thalassaemia&f%5B0%5D=ema_search_topics%3A61."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40005\u2010017\u20100371\u20103"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2019.27.1.19"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coche.2025.101093"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2856"},{"key":"e_1_2_8_10_1","unstructured":"European Medicines Agency \u201cICH M15 Guideline on General Principles for Model\u2010Informed Drug Development Step 2b \u201d2024 accessed June 22 2025 https:\/\/www.ema.europa.eu\/en\/ich\u2010m15\u2010guideline\u2010general\u2010principles\u2010model\u2010informed\u2010drug\u2010development\u2010step\u20102b\u2010scientific\u2010guideline#:~:text=This%20guideline%20defines%20an%20harmonised%20framework%20for%20evaluating planning%20and%20regulatory%20interactions 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