{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:49:33Z","timestamp":1791848973787,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The International Conference on Harmonization (ICH) E14 document was revised in 2015 to allow concentration\u2013corrected QT interval (C\u2013QTc) analysis to be applied to data from early clinical pharmacology studies to exclude a small drug\u2010induced effect on QTc. Provided sufficiently high concentrations of the drug are obtained in the first\u2010in\u2010human (FIH) study, this approach can be used to obviate the need for a designated thorough QT (TQT) study. The E14 revision has resulted in a steady reduction in the number of TQT studies and an increased use of FIH studies to evaluate electrocardiogram (ECG) effects of drugs in development. In this review, five examples from different sponsors are shared in which C\u2013QTc analysis was performed on data from FIH studies. Case\u00a01 illustrates a clearly negative C\u2013QTc evaluation, despite observations of QTc prolongation at high concentrations in nonclinical studies. In case\u00a02 C\u2013QTc analysis of FIH data was performed prior to full pharmacokinetic characterization in patients, and the role of nonclinical assays in an integrated risk assessment is discussed. Case\u00a03 illustrates a positive clinical C\u2013QTc relationship, despite negative nonclinical assays. Case\u00a04 demonstrates a strategy for characterizing the C\u2013QTc relationship for a nonracemic therapy and formulation optimization, and case\u00a05 highlights an approach to perform a preliminary C\u2013QTc analysis early in development and postpone the definitive analysis until proof of efficacy is demonstrated. The strategy of collecting and storing ECG data from FIH studies to enable an informed decision on whether and when to apply C\u2013QTc analysis to obviate the need for a TQT study is described.<\/jats:p>","DOI":"10.1002\/jcph.2095","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T03:29:45Z","timestamp":1654486185000},"page":"1480-1500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["ECG Evaluation as Part of the Clinical Pharmacology Strategy in the Development of New Drugs: A Review of Current Practices and Opportunities Based on Five Case Studies"],"prefix":"10.1002","volume":"62","author":[{"given":"Borje","family":"Darpo","sequence":"first","affiliation":[{"name":"Clario  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Borin","sequence":"additional","affiliation":[{"name":"Clinical and Translational Pharmacology Theravance Biopharma US, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Ferber","sequence":"additional","affiliation":[{"name":"Statistik Georg Ferber GmbH  Riehen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald R.","family":"Galluppi","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals, Inc.  Marlborough Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth C.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals, Inc.  Marlborough Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishani","family":"Landry","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Translational Medicine Eisai  Nutley New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lo","sequence":"additional","affiliation":[{"name":"Clinical and Translational Pharmacology Theravance Biopharma US, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Rege","sequence":"additional","affiliation":[{"name":"Alkermes, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Reyderman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Translational Medicine Eisai  Nutley New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Alkermes, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals, Inc.  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