{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:00:39Z","timestamp":1781632839999,"version":"3.54.5"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Cancer Institute"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We compare our experience with three pharmacometric modeling workflows for simulating alternative dosing regimens of\u00a0atezolizumab: (1) the gold-standard, NONMEM software used in combination with R, (2) the R-based package RxODE, and (3) the\u00a0recently developed Julia-based software Pumas, discussing the advantages and limitations of each.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Our prior work demonstrated that an extended-interval dosing regimen (840 mg q6w) following two standard loading doses\u00a0maintained efficacy while having a nonsignificant exposure-response relationship with adverse events. In the original analysis, the\u00a0virtual population was generated in R, simulations performed using NONMEM, and data analysis and visualization then conducted in\u00a0R. In the present study, we perform the full workflow within R using RxODE for simulation and also recreate this workflow using\u00a0Pumas in Julia. Pharmacokinetic parameters and graphical output, as well as the processing speed for each method were\u00a0compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three approaches generated comparable virtual populations, key exposure metrics of CMAX, CMIN, and Weekly AUC,\u00a0and data visualizations of the simulated serum concentrations. However, there were differences in how quickly each software\u00a0simulated the entire seven cycle dataset, with Pumas simulating 33,273 obs\/second, NONMEM 4,782 obs\/sec, and RxODE 251\u00a0obs\/sec. Due to this large difference, the dataset was broken into individual cycles, where NONMEM and RxODE performed\u00a0comparably at 2041-3337 obs\/sec, while Pumas simulated 48,122-69,168 obs\/sec.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>All three software produced comparable results. Ultimately, the choice should be based on the modeler\u2019s specific needs\u00a0and limitations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-025-03974-9","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:05:18Z","timestamp":1768802718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A comparison of pharmacometric software programs for atezolizumab population pharmacokinetic simulation"],"prefix":"10.1007","volume":"82","author":[{"given":"Yi","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatobi","family":"Arisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Corvalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Peer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Figg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"issue":"14","key":"3974_CR1","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1056\/NEJMoa1917346","volume":"383","author":"RS Herbst","year":"2020","unstructured":"Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH et al (2020) Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. 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All remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The analysis is comparing pharmacokinetic software programs using simulated data. Thus, there are no consents, IRB approval, or other patient protection concerns. Clinical trial number: not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human ethics and consent to participate"}},{"value":"The views, information, or content, and conclusions presented do not necessarily represent the official position or policy of, nor should any official endorsement be inferred on the part of the Clinical Center or the National Cancer Institute, the National Institutes of Health, or the Department of Health and Human Services.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}],"article-number":"42"}}