著者

矢船 明史 竹内 正弘 成川 衛

出版者

日本臨床薬理学会

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.31, no.6, pp.705-713, 2000-11-30 (Released:2010-06-28)

参考文献数

20

被引用文献数

1

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Since nonlinear mixed effects model is statistically quite complicated, it is not possible to obtain the analytical forms of the marginal mean and its corresponding covariance matrix for observations. To circumvent this issue, a first-order Taylor series expansion is generally employed to approximate a nonlinear model with a linear form additive in inter-subject random effects. This linear approximation is based on the assumption that the parameter variation among subjects is negligible, which is quite hard to satisfy in actual clinical data analyses. Consequently, the linear approximation probably leads to inconsistent estimators. This paper describes the statistical issues regarding the first-order linear approximation in nonlinear mixed effects models.

著者

矢船 明史 津谷 喜一郎

出版者

日本臨床薬理学会

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.27, no.3, pp.635-645, 1996-09-30 (Released:2010-06-28)

参考文献数

55

被引用文献数

4 7 2

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There has been an increasing number of clinical reports in the West to suggest that hepatotoxic reactions can be induced by herbal preparations including skullcap of Scutellaria species. In Japan, the root of Scutellaria baicalensis (Scutellariae Radix) is used under the name of Ogon, which is included in many kinds of Kampo formulations, such as Sho-saiko-to widely used for treating hepatic disorders. Reviewing the Information on Adverse Reactions to Drugs published by the Ministry of Health and Welfare of Japan, we found 22 cases of liver and biliary system reactions caused by Kampo formulations from 1989 through 1993, and in 20 of the cases, six types of Kampo formulations including Ogon were suspected as the cause of the reactions. In two clinical reports of pulmonary damage due to Sho-saiko-to, Lymphocyte Stimulation Test indicated that Ogon was the causative factor for the damage. Although there have been no reports to indicate that Ogon can actually cause liver damage, the results of our review strongly suggest the necessity for surveillance of the possibility of hepatotoxic reactions caused by Ogon.

著者

竹内 正弘 矢船 明史 成川 衛

出版者

日本臨床薬理学会

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.31, no.5, pp.659-665, 2000-09-30 (Released:2010-06-28)

参考文献数

26

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Nonlinear mixed effects models are often used for the analysis of repeated measure ments in clinical trials. A typical example is population pharmacokinetic analysis. Due to the statistical complexity, careful attention must be paid to some statistical issues in order to obtain reliable and robust results. This paper provides a description of the notes on the use of nonlinear mixed effects models for the analysis of repeated measurements in clinical trials. Three main issues are discussed in this paper: 1) a first-order lineariza tion, 2) a missing data, and 3) a measurement error.