{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:23:42Z","timestamp":1782386622226,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Whether a compound prolongs cardiac repolarization independent of changes in beat rate is a critical question in drug research and development. Current practice is to resolve this in two steps. First, the QT interval is corrected for the influence of rate and then statistical significance is tested. There is renewed interest in improving the sensitivity of nonclinical corrected QT interval (QTc) assessment with modern studies having greater data density than previously utilized. The current analyses examine the effects of moxifloxacin or vehicle on the QT interval in nonhuman primates (NHPs) using a previously described one\u2010step method. The primary end point is the statistical sensitivity of the assessment. Publications suggest that for a four animal\u00a0crossover (4 \u00d7 4) in NHPs the minimal detectable difference (MDD) is greater than or equal to 10\u2009ms, whereas in an eight animal crossover the MDD is ~6.5\u2009ms. Using the one\u2010step method, the MDD for the four animal NHP assessments was 3\u2009ms. In addition, the one\u2010step model accounted for day\u2010to\u2010day differences in the heart rate and QT\u2010rate slope as well as drug\u2010induced changes in these parameters. This method provides an increase in the sensitivity and reduces the number of animals necessary for detecting potential QT change and represents \u201cbest practice\u201d in nonclinical QTc assessment in safety pharmacology studies.<\/jats:p>","DOI":"10.1111\/cts.13625","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T05:41:06Z","timestamp":1695188466000},"page":"2253-2264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The \u201cOne\u2010Step\u201d approach for QT analysis increases the sensitivity of nonclinical <scp>QTc<\/scp> analysis"],"prefix":"10.1111","volume":"16","author":[{"given":"Derek J.","family":"Leishman","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Charles River Laboratories  Mattawan Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-1124","authenticated-orcid":false,"given":"D. Adam","family":"Lauver","sequence":"additional","affiliation":[{"name":"Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Bailie","sequence":"additional","affiliation":[{"name":"Certara  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Roche","sequence":"additional","affiliation":[{"name":"Charles River Laboratories  Mattawan Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Anonymous.ICH E14: the clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010 antiarrhythmic drugs.2005a."},{"key":"e_1_2_10_3_1","unstructured":"Anonymous.ICH S7B: the non\u2010clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals.2005b."},{"key":"e_1_2_10_4_1","unstructured":"Anonymous.ICH E14 Guideline: The Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs\u2010Questions & Answers (R3).2015."},{"key":"e_1_2_10_5_1","unstructured":"Anonymous.ICH E14\/S7B Implementation Working Group \u2013 Clinical and Nonclinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential.2022. 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