{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:54:25Z","timestamp":1781690065112,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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; Syst Pharma"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Clinical trials in asthma and chronic obstructive pulmonary disease often use exacerbation risk as the primary endpoint. However, exacerbations occur with low frequency, leading to long and costly clinical trials. Home\u2010measured spirometry, which is becoming more common, provides an alternative and has previously been used to shorten the necessary trial duration. In this work, we develop a\n                    <jats:italic>mixed\u2010effects hidden Markov model<\/jats:italic>\n                    (MEHMM) for analyzing home\u2010measured\n                    <jats:italic>peak expiratory flow<\/jats:italic>\n                    (PEF), combining an observation model with a latent two\u2010state disease process representing sustained periods of high and low PEF, respectively. An inference framework is implemented to estimate fixed and random effects together with measures of uncertainty. Data from a phase 2b dose\u2010finding study of velsecorat in asthma are used to investigate dose\u2013response relationships, complemented by an extensive simulation study. The results demonstrate reliable estimation of parameters and identify statistically significant treatment effects on multiple model components. These findings support the use of latent disease\u2010state models for extracting meaningful information from home\u2010measured spirometry.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70281","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:51:01Z","timestamp":1780732261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling Peak Expiratory Flow in Patients With Asthma and Quantifying Treatment Effects Using a Mixed\u2010Effects Hidden Markov Model"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8851-4374","authenticated-orcid":false,"given":"Ludvig","family":"Jakobsson","sequence":"first","affiliation":[{"name":"Department of Mathematical Sciences Chalmers University of Technology and University of Gothenburg  Gothenburg Sweden"},{"name":"Fraunhofer\u2010Chalmers Research Centre for Industrial Mathematics  Gothenburg Sweden"},{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-017X","authenticated-orcid":false,"given":"Marcus","family":"Baaz","sequence":"additional","affiliation":[{"name":"Fraunhofer\u2010Chalmers Research Centre for Industrial Mathematics  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7411-2967","authenticated-orcid":false,"given":"Jacob","family":"Leander","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Gerlee","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences Chalmers University of Technology and University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-8037","authenticated-orcid":false,"given":"Mats","family":"Jirstrand","sequence":"additional","affiliation":[{"name":"Fraunhofer\u2010Chalmers Research Centre for Industrial Mathematics  Gothenburg Sweden"},{"name":"Department of Electrical Engineering Chalmers University of Technology  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04176"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00180811"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S3385"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.105919"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2021.100793"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.10.053"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.156489"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12748"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(17)30218\u20107"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.106175"},{"key":"e_1_2_10_12_1","unstructured":"AstraZeneca A Phase 2b Randomised Double\u2010Blind Placebo\u2010Controlled Dose Range\u2010Finding Study to Assess Efficacy and Safety of Multiple Dose Levels of Inhaled AZD8630 Given Once Daily for 12\u2009Weeks in Adults With Uncontrolled Asthma at Risk of Exacerbations (LEVANTE)accessed at March 23 2026 https:\/\/clinicaltrials.gov\/study\/NCT06529419."},{"key":"e_1_2_10_13_1","unstructured":"Amgen A Phase 2 Randomized Double\u2010Blind Placebo\u2010Controlled Dose Ranging Study to Assess the Efficacy and Safety of Rocatinlimab in Adult Subjects With Moderate\u2010to\u2010Severe Asthmaaccessed at March 23 2026 https:\/\/clinicaltrials.gov\/study\/NCT06376045."},{"key":"e_1_2_10_14_1","unstructured":"AstraZeneca A Phase IIa Randomised Double Blind Placebo Controlled Parallel Arm Multi\u2010Centre Study to Evaluate the Efficacy and Safety of Mitiperstat (AZD4831) for 12\u201324\u2009Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)accessed at April 10 2026 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