{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:27:10Z","timestamp":1753878430735,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A \u201cone\u2010step\u201d method which combined the heart rate correction and statistical analysis for conscious nonhuman primate (NHP) QTc assessment was recently published. The principles of this method are applicable to other species. In the current analysis, we demonstrate the utility of the technique in conscious dog QTc studies. Two studies in male dogs (<jats:italic>n<\/jats:italic>\u2009=\u20098 and <jats:italic>n<\/jats:italic>\u2009=\u20097) implanted with telemetry devices were used. In both studies, treatments were randomized and all animals received all treatments. In the primary study, the effect on QTc of moxifloxacin was compared with vehicle. Each treatment (vehicle and moxifloxacin) was given on two separate occasions. In the second study, dogs were given vehicle or dofetilide. Conventional QTc analysis was compared with the \u201cone\u2010step\u201d method. The effect on QTc relative to vehicle was determined along with the median minimal detectable difference. As expected, both moxifloxacin and dofetilide gave QTc increases with a maximum of ~\u200920\u2009ms. There was a significant increase in the sensitivity to detect a QTc effect when using the \u201cone\u2010step\u201d method. The minimal detectable difference was 1.6\u2009ms for the \u201cone\u2010step\u201d method compared with 6.2\u2009ms for the conventional method. These analyses are consistent with the increased sensitivity described for the \u201cone\u2010step\u201d method applied to studies in NHP. The increased sensitivity should enhance the ability to support an integrated assessment of the QTc prolongation liability for new drugs.<\/jats:p>","DOI":"10.1111\/cts.70046","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T13:33:32Z","timestamp":1728999212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A \u201cone\u2010step\u201d approach to heart rate correction and statistical analysis applied to conscious dog <scp>QTc<\/scp> studies"],"prefix":"10.1111","volume":"17","author":[{"given":"Derek D.","family":"Best","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Abernathy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek J.","family":"Leishman","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2137"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2029"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2023.107265"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2023.107270"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13625"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2006.02.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2005.07.002"},{"key":"e_1_2_10_10_1","unstructured":"Anonymous.ICH E14\/S7B Q&As training material examples supplemental file.2022."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2023.107253"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2021.107067"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/00031305.1980.10483031"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/43.suppl_2.69"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2014.12.008"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498259209053133"},{"key":"e_1_2_10_17_1","article-title":"Demonstrating the statistical and pharmacological sensitivity of nonclinical QTc analysis using a dofetilide dose\u2010response in nonhuman primates","author":"Leishman DJ","year":"2024","journal-title":"J Pharmacol Toxicol Methods"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3283"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2024.107528"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T13:34:05Z","timestamp":1729863245000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":18,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/cts.70046"],"URL":"https:\/\/doi.org\/10.1111\/cts.70046","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"type":"print","value":"1752-8054"},{"type":"electronic","value":"1752-8062"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70046"}}