{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:57:07Z","timestamp":1791863827021,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013739","name":"Pfizer Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The Web\u2010Accessible Population Pharmacokinetic Service (WAPPS) project generates individually predicted pharmacokinetic (PK) profiles and tailored prophylactic treatment regimens for haemophilic patients, which rely on a set of population PK (PopPK) models providing concentrate\u2010specific priors for the Bayesian forecasting methodology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To describe the predictive performance of the WAPPS PopPK models in use on the WAPPS\u2010Hemo platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data for modelling include dense PK data obtained from industry sponsored and independent PK studies, and dense and sparse data accumulated through WAPPS\u2010Hemo. WAPPS PopPK models were developed via non\u2010linear mixed\u2010effect modelling taking into account the effects of covariates and between\u2010individual\u2014and sometimes between\u2010occasion\u2014variability. Model evaluation consisted of (a) prediction\u2010corrected Visual Predictive Check (pcVPC), (b) Limited Sampling Analysis (LSA) and (c) repeated hold\u2010out cross\u2010validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010three WAPPS PopPK models built on data from 3188 patients (ages 1\u201078\u00a0years) under treatment by factor VIII or IX products (FVIII, FIX) were evaluated. Overall, models exhibit excellent performance characteristics. The pcVPC shows that the observed PK data fall within acceptable 90% interpercentile predictive bands. A slight overprediction beyond the expected half\u2010life, an anticipated result of using sparse data, occurs for some models. The LSA results in lower than 3% of relative error for FVIII and FIX products and 16% for engineered FIX products. Cross\u2010Validation analysis yields relative errors lower than 1.5% and 1.4% in estimates of half\u2010life and time to 0.02\u00a0IU\/mL, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The WAPPS\u2010Hemo models consistently showed excellent performance characteristics for the intended use for Bayesian forecasting of individual PK profiles.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13977","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T09:15:59Z","timestamp":1586769359000},"page":"384-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Development and evaluation of the population pharmacokinetic models for FVIII and FIX concentrates of the WAPPS\u2010Hemo project"],"prefix":"10.1111","volume":"26","author":[{"given":"Dagmar M.","family":"Hajducek","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chelle","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Hermans","sequence":"additional","affiliation":[{"name":"Haemostasis and Thrombosis Unit Division of Haematology Cliniques universitaires Saint\u2010Luc Universit\u00e9 catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-8766","authenticated-orcid":false,"given":"Alfonso","family":"Iorio","sequence":"additional","affiliation":[{"name":"McMaster\u2010Bayer Endowed Research Chair for Clinical Epidemiology of Congenital Bleeding Disorders Department of Medicine Department of Health Research Methods, Evidence and Impact McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-2603","authenticated-orcid":false,"given":"Alanna","family":"McEneny\u2010King","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-1653","authenticated-orcid":false,"given":"Andrea","family":"Edginton","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2196\/resprot.6558"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01664.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-470898"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1677700"},{"issue":"01","key":"e_1_2_9_6_1","first-page":"180","article-title":"Project on factor VIII\/Factor IX Pharmacokinetics of the Factor VIII\/Factor IX Scientific Standardization Committee of the 1sth. Measurement of Factor VIII pharmacokinetics in routine clinical practice","volume":"11","author":"Bjorkman S","year":"2013","journal-title":"J Thromb Haemost"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2196\/resprot.6559"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00809-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-019-09637-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0277-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544100-00004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13242"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006745"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14469"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13271"},{"key":"e_1_2_9_17_1","volume-title":"Annual Meeting of the Population Approach Group in Europe","author":"Wicha S","year":"2018"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13444"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14292"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2018.07.010"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13215"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14394"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13977","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13977","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.13977","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:02:48Z","timestamp":1693918968000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.13977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,13]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/hae.13977"],"URL":"https:\/\/doi.org\/10.1111\/hae.13977","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,13]]},"assertion":[{"value":"2019-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}