{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T01:19:41Z","timestamp":1752283181993,"version":"3.40.5"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vertex Pharmaceuticals Incorporated"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objectives<\/jats:title><jats:p>Cystic fibrosis (CF) is a rare genetic disease characterized by life-shortening lung function decline. Ivacaftor, a CF transmembrane conductance regulator modulator (CFTRm), was approved in 2012 for people with CF with specific gene mutations. We used real-world evidence of 5-year mortality impacts of ivacaftor in a US registry population to validate a CF disease-progression model that estimates the impact of ivacaftor on survival.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>The model projects the impact of ivacaftor vs. standard care in people with CF aged \u22656 years with<jats:italic>CFTR<\/jats:italic>gating mutations by combining parametric equations fitted to historical registry survival data, with mortality hazards adjusted for fixed and time-varying person-level characteristics. Disease progression with standard care was derived from published registry studies and the expected impact of ivacaftor on clinical characteristics was derived from clinical trials. Individual-level baseline characteristics of the registry ivacaftor-treated population were entered into the model; 5-year model-projected mortality with credible intervals (CrIs) was compared with registry mortality to evaluate the model\u2019s validity.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Post-calibration 5-year mortality projections closely approximated registry mortality in populations treated with standard care (6.4% modeled [95% CrI: 5.3% to 7.6%] vs. 6.0% observed) and ivacaftor (3.4% modeled [95% CrI: 2.7% to 4.4%] vs. 3.1% observed). The model accurately predicted 5-year relative risk of mortality (0.53 modeled [0.47 to 0.60] vs. 0.51 observed) in people treated with ivacaftor vs. standard care.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Modeled 5-year survival projections for people with CF initiating ivacaftor vs. standard care align closely with real-world registry data. Findings support the validity of modeling CF to predict long-term survival and estimate clinical and economic outcomes of CFTRm.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0283479","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T17:38:07Z","timestamp":1681321087000},"page":"e0283479","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Calibration and validation of modeled 5-year survival predictions among people with cystic fibrosis treated with the cystic fibrosis transmembrane conductance regulator modulator ivacaftor using United States registry data"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3454-9184","authenticated-orcid":true,"given":"Lisa J.","family":"McGarry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Bhaiwala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conor","family":"Chandler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5255-2777","authenticated-orcid":true,"given":"Christopher G.","family":"Pelligra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime L.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-4847","authenticated-orcid":true,"given":"Theodore G.","family":"Liou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"issue":"1","key":"pone.0283479.ref001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: a global perspective.","volume":"8","author":"SC Bell","year":"2020","journal-title":"Lancet Respir Med."},{"issue":"8","key":"pone.0283479.ref002","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/S2213-2600(16)00023-0","article-title":"Progress in therapies for cystic fibrosis","volume":"4","author":"K De Boeck","year":"2016","journal-title":"Lancet Respir Med"},{"issue":"10059","key":"pone.0283479.ref003","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis.","volume":"388","author":"JS Elborn","year":"2016","journal-title":"Lancet"},{"issue":"9678","key":"pone.0283479.ref004","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/S0140-6736(09)60327-5","article-title":"Cystic fibrosis.","volume":"373","author":"BP O\u2019Sullivan","year":"2009","journal-title":"Lancet"},{"journal-title":"2019 Patient Registry: Annual Data Report","year":"2020","author":"Cystic Fibrosis Foundation","key":"pone.0283479.ref005"},{"journal-title":"2015 Patient Registry: Annual Data Report","year":"2016","author":"Cystic Fibrosis Foundation","key":"pone.0283479.ref006"},{"issue":"3","key":"pone.0283479.ref007","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/00005176-200209000-00004","article-title":"Consensus report on nutrition for pediatric patients with cystic fibrosis","volume":"35","author":"D Borowitz","year":"2002","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"7","key":"pone.0283479.ref008","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1164\/rccm.201207-1160OE","article-title":"Cystic fibrosis pulmonary guidelines. 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