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However, mixed models for repeated measures (MMRM) have been shown to be poorly specified in study protocols. The magnitude of a resulting T1E rate inflation is still unknown. This investigation aims to quantify the magnitude of the T1E rate inflation depending on the type and number of unspecified model items as well as different trial characteristics. We simulated a randomized, double\u2010blind, parallel group, phase III clinical trial under the assumption that there is no treatment effect at any time point. The simulated data was analysed using different clusters, each including several MMRMs that are compatible with the imprecise pre\u2010specification of the MMRM. T1E rates for each cluster were estimated. A significant T1E rate inflation could be shown for ambiguous model specifications with a maximum T1E rate of 7.6% [7.1%; 8.1%]. The results show that the magnitude of the T1E rate inflation depends on the type and number of unspecified model items as well as the sample size and allocation ratio. The imprecise specification of nuisance parameters may not lead to a significant T1E rate inflation. However, the results of this simulation study rather underestimate the true T1E rate inflation. In conclusion, imprecise MMRM specifications may lead to a substantial inflation of the T1E rate and can damage the ability to generate confirmatory evidence in pivotal clinical trials.<\/jats:p>","DOI":"10.1002\/pst.2328","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T05:23:31Z","timestamp":1690781011000},"page":"1046-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>Type\u2010I<\/scp>\u2010error rate inflation in mixed models for repeated measures caused by ambiguous or incomplete model specifications"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-0495","authenticated-orcid":false,"given":"Sebastian","family":"H\u00e4ckl","sequence":"first","affiliation":[{"name":"Hannover Medical School Institute of Biostatistics  Hannover Niedersachsen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-3219","authenticated-orcid":false,"given":"Armin","family":"Koch","sequence":"additional","affiliation":[{"name":"Hannover Medical School Institute of Biostatistics  Hannover Niedersachsen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lasch","sequence":"additional","affiliation":[{"name":"European Medicines Agency  Amsterdam Noord\u2010Holland The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"International Conference on Harmonisation (ICH).Statistical Principles for Clinical Trials (ICH E9). 1998; 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