{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:02:33Z","timestamp":1789614153856,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Stability assessment of vaccine drug products typically requires years of data collection. Accelerated stability studies offer a practical alternative by leveraging high\u2010temperature data collected over shorter time periods. We model degradation using arbitrary\n                    <jats:italic>n<\/jats:italic>\n                    th order kinetics and derive a closed\u2010form solution that enables extrapolation across time and temperature. We compare interval estimation methods including the delta method, bootstrap resampling, and Bayesian inference and propose a frequentist\u2013Bayesian hybrid (FBH) posterior approximation framework based on a multivariate Student's\n                    <jats:italic>t<\/jats:italic>\n                    \u2010distribution. FBH is closely related to objective Bayesian inference under noninformative priors in simple Gaussian settings and fully propagates uncertainty in both model parameters and residual variance. Simulation results show that FBH outperforms standard approaches by consistently achieving nominal coverage, particularly in small\u2010sample settings where competing methods exhibit undercoverage. The approach provides well\u2010calibrated confidence and prediction intervals while maintaining computational efficiency comparable to analytical methods and avoiding the cost of full posterior sampling. The methodology is illustrated using two vaccine development case studies and implemented in the AccelStab R package.\n                  <\/jats:p>","DOI":"10.1002\/pst.70116","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:36:54Z","timestamp":1788572214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accelerated Stability Studies: A Frequentist\u2013Bayesian Hybrid Simulation Approach Implemented in the\n                    <scp>AccelStab<\/scp>\n                    R Package"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6183-387X","authenticated-orcid":false,"given":"Bernard G.","family":"Francq","sequence":"first","affiliation":[{"name":"GSK  Rixensart Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-4744","authenticated-orcid":false,"given":"Nikolaos","family":"Giannelos","sequence":"additional","affiliation":[{"name":"GSK  Rixensart Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6869-8802","authenticated-orcid":false,"given":"Raymundo","family":"Sanchez","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Paludi","sequence":"additional","affiliation":[{"name":"GSK  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14020430"},{"key":"e_1_2_12_3_1","unstructured":"European Medicines Agency \u201cPRIME: Priority Medicines \u201dhttps:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\/research\u2010development\/prime\u2010priority\u2010medicines."},{"key":"e_1_2_12_4_1","unstructured":"U.S. Food and Drug Administration \u201cEmergency Use Authorization for Vaccines Explained \u201dhttps:\/\/www.fda.gov\/vaccines\u2010blood\u2010biologics\/vaccines\/emergency\u2010use\u2010authorization\u2010vaccines\u2010explained."},{"key":"e_1_2_12_5_1","unstructured":"ICH \u201cEvaluation of Stability Data \u201dhttps:\/\/database.ich.org\/sites\/default\/files\/Q1E."},{"key":"e_1_2_12_6_1","unstructured":"ICH \u201cQuality of Biotechnological Products: Stability Testing of Biotechnological\/Biological Products \u201dhttps:\/\/database.ich.org\/sites\/default\/files\/Q5C."},{"key":"e_1_2_12_7_1","unstructured":"WHO Guidelines on the Stability Evaluation of Vaccines for Use under Extended Controlled Temperature Conditions Annex 5 TRS No 999 (WHO 2016) https:\/\/www.who.int\/publications\/m\/item\/ectc\u2010annex\u20105\u2010trs\u2010no\u2010999."},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9101114"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11071153"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121143"},{"key":"e_1_2_12_11_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) \u201cICH Harmonised Tripartite Guidance Q1A(R2) \u201dStability Testing of New Drug Substances and Products (ICH 2003) 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