title: Sex-related differences in QTc effects potential of drugs.
abstract: The objective of this study was to examine the drug-induced sex differences in corrected QT (QTc) interval by re-analyzing the data collected in thorough QT studies submitted to the US Food and Drug Administration (FDA). We examined 64 studies available in the FDA database by performing a time-matched, baseline adjusted ANCOVA on the QTc response stratified by sex. We used several summaries to capture the differences between males and females in drug response QTc effects. They included sample means, upper confidence intervals, and areas under the curves. At baseline, females tend to have a higher QTc response than males. After treatment, various summaries suggest that females tend to have a higher QTc effect than males. However, the magnitude of the difference is small and is often not statistically significant. Several limitations can be raised about these available data: 1) available QT studies were not designed to examine the sex differences in QTc effects, 2) the findings were undermined by large variations seen in QT data, and 3) our summary statistics are descriptive in nature and are not for inferential purposes. Nonetheless, the results suggest that females tend to have a higher QTc effect than males, although the difference tends to be small. Further research is needed to formally address the question.
authors.affiliation: Division of Biometrics 1, Office of Biostatistics/Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA. Phillip.Dinh@fda.hhs.gov
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Steve
authors.initials: S
authors.lastname: Bai
authors.forename: George
authors.initials: G
authors.lastname: Kordzakhia
mesh_terms: D000704:Analysis of Variance; D019540:Area Under Curve; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D004364:Pharmaceutical Preparations; D012737:Sex Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004364:Pharmaceutical Preparations