Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics

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Background : It is well-known that the QT interval and the RR change in the same direction on electrocardiograms (ECGs). This change appears to be modified by various factors such as sex, age, and race. Accordingly, it is necessary to investigate the joint distribution of QT and RR in resting ECGs of healthy young Japanese men, before undertaking trials to test the effect of drugs on QT. To eliminate the effects of RR on QT and obtain new values that are independent of the RR intervals, many formulas have been proposed. Among them, Bazett's and Fridericia's corrections are the most widely used. We compared these two correction methods by means of correlation coefficient and determined which one was best fit to determine the independence between QTc and RR.
Methods : By using all cases in the subject population, the QTc values corrected according to Bazett (QTcB) and Fridericia (QTcF) were calculated. The correlation coefficients between QTcB and RR, and between QTcF and RR were calculated. In doing such a comparison, the usefulness of these two corrections was assessed.
Results : The mean of the conditional QT distribution, given linear RR, increased along with the increase of RR. We found that the correlation coefficient between QTcF and RR was almost null, whereas that between QTcB and RR was -0.5 and it was statistically significant.
Conclusion : We showed that the mean of the conditional distribution of QT given RR was closely approximated by Fridericia's correction formula. We also transformed QT to QTcF by means of Fridericia's correction formula and succeeded in obtaining QTcF values that were statistically independent of the RR. From these results, we conclude that the application of Fridericia's correction is more suitable for the evaluation of QT in resting ECGs of healthy young Japanese men.

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Recent advances in pharmacogenomics (PGx) propose the clinical application of genome information as individualized medicine. However, the matter of how the citizens in Japan find the PGx-based medicine, including clinical research remains to be addressed. Questionnaires concerning genome science and PGx were sent to citizens in Japan through the internet system. In the questionnaires, we provided information on PGx in order to evaluate the educational effects on the understanding and/or approval of PGx-based medicine. The majority of citizens in Japan have an interest in genome science and accept its application to medical practice. However, individualized medicine based on genome information is not fully understood. About one-third of the subjects expressed hesitation to participate in PGx-based clinical research prior to reading the information provided in the questionnaire, because of possible illegal uses of their genome samples and personal information. Interestingly, during the questionnaire they had a tendency to change their mind to affirmative because of the information provided concerning how PGx-based medicines or clinical research projects are designed and performed in order to prevent misunderstanging of participants. The citizens in Japan have an interest in genome science ; however, PGx-based medicine has not been fully understood. More information concerning PGx-based medicine, including clinical research, should be provided for citizens in general in order to achieve individualized medicine based on genome science.

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