計量生物学

編集者の序

2005年計量生物セミナー臨床試験における統計学上の論点

上坂浩之, 森川敏彦, 岩崎学, 松井茂之

2006 年 27 巻 Special_Issue 号 p. S1-S2
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S1

ジャーナルフリー

PDF形式でダウンロード (56K)
2005年計量生物セミナー「臨床評価における統計学上の論点」に参加して

森和彦

2006 年 27 巻 Special_Issue 号 p. S3-S4
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S3

ジャーナルフリー

PDF形式でダウンロード (65K)

話題1：Points to Consider on Adjustment for Baseline Covariates

Points to Consider on Adjustment for Baseline Covariatesに関する編集者のまとめ

岩崎学

2006 年 27 巻 Special_Issue 号 p. S6-S7
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S6

ジャーナルフリー

PDF形式でダウンロード (90K)
Points to Consider on Adjustment for Baseline Covariatesへの意見

萩野篤司

2006 年 27 巻 Special_Issue 号 p. S8-S15
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S8

ジャーナルフリー

抄録を表示する抄録を非表示にする

In May 2003, the Committee for Proprietary Medicinal Products (CPMP) of the European Agency for the Evaluation of Medicinal Products (EMEA) issued a guidance regarding the adjustment for covariates entitled “Points to Consider on Adjustment for Baseline Covariates”. This article provides a summary of the guidance and specifically discusses the use of dynamic allocation from the viewpoint that advocates the necessity of pre-stratification in clinical trials.

抄録全体を表示

PDF形式でダウンロード (164K)
共変量による調整について

清見文明, 西田朋由, 西島啓二

2006 年 27 巻 Special_Issue 号 p. S16-S21
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S16

ジャーナルフリー

抄録を表示する抄録を非表示にする

In randomized clinical trials, continuous outcome measures are often used as endpoints. For qualitative covariates associated with the primary endpoint, stratified randomization is frequently used in order to ensure balance between treatment groups. Quantitative covariates associated with the primary endpoint are also frequently prespecified. “Points to Consider on Adjustment for Baseline Covariates” (2003) strongly recommends analysis of covariance (ANCOVA) as a primary analysis for such trials to improve the precision and compensate for imbalance. This paper also recommends ANCOVA, but also accepts the two sample t-test under a small loss of precision and unlikely imbalances of covariates. Interactions between treatment group and covariates will not be generally included in the primary analysis model. Even if they exist, differences between least square means estimated by the ANCOVA model without interactions and differences between arithmetic means of treatment groups are equal in expectation under several assumptions. Therefore, it can be said the ANCOVA without interactions is better than the usual t-test in precision. An example of the preferred way to show ANCOVA results is given. Also the interpretation of least square mean is briefly discussed.

抄録全体を表示

PDF形式でダウンロード (179K)
PtC on Adjustment for Baseline Covariatesに関して

服部聡

2006 年 27 巻 Special_Issue 号 p. S22-S25
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S22

ジャーナルフリー

抄録を表示する抄録を非表示にする

We provide further discussion on statistical inference for treatment effects based on possibly mis-specified models. Mainly we consider survival analysis.

抄録全体を表示

PDF形式でダウンロード (152K)
討論の部

2006 年 27 巻 Special_Issue 号 p. S26-S30
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S26

ジャーナルフリー

PDF形式でダウンロード (118K)

話題2：Points to Consider on Missing Data

Points to Consider on Missing Dataに関する編集者のまとめ
臨床試験における欠測の問題

松井茂之

2006 年 27 巻 Special_Issue 号 p. S31-S32
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S31

ジャーナルフリー

PDF形式でダウンロード (78K)
臨床評価における統計学上の論点：欠測値の諸問題

渡辺秀章, 田崎武信

2006 年 27 巻 Special_Issue 号 p. S33-S44
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S33

ジャーナルフリー

抄録を表示する抄録を非表示にする

In clinical trials, missing data often happens for a variety of reasons, such as dropouts, making it difficult to analyze the primary variable measured longitudinally and to interpret the results of the primary analysis. While handling missing data sometimes causes bias in the results, there have been no established statistical approaches applied to missing data in appropriate situations. In November 2001, Committee for Proprietary Medical Product of the European Medicines Agency, issued “Points to Consider (PtC) on Missing Data”, which focuses on several points that should be taken into account when handling missing data in clinical trials. In this paper, we review the contents of this PtC, which assumes that the primary analysis is based on the ITT principle, and discuss some of the approaches for handling missing data and the difficulties in interpreting these results.

抄録全体を表示

PDF形式でダウンロード (222K)
臨床的アプローチと統計的アプローチ

松井研一

2006 年 27 巻 Special_Issue 号 p. S45-S49
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S45

ジャーナルフリー

抄録を表示する抄録を非表示にする

In any clinical trial or epidemiological study , missing data will occur. The problem in dealing with missing data are discussed from both clinical and statistical view points. Clinical approaches (e.g. LOCF) are easy to understand for physicians and are often appropriate for considering clinical background settings. But they seem to be less objective compared with statistical approaches , including multiple imputation based on “propensity score”. Further efforts should be made to bridge these two approaches in order to deal with missing data appropriately.

抄録全体を表示

PDF形式でダウンロード (150K)
Points to Consider on Missing Dataへのコメント

松井茂之

2006 年 27 巻 Special_Issue 号 p. S50-S54
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S50

ジャーナルフリー

抄録を表示する抄録を非表示にする

The “Point to Consider (PtC) on Missing Data” issued by EMEA implicitly postulates strict intention-to-treat analyses and discusses various methods for imputation of missing data, including parametric imputation methods. Imputation may not be relevant to situations after the occurrence of particular events such as a terminating event like death or clinical events that can largely alter the value of the response variable. Possibility of non-ignorable missing mechanisms when adopting parametric methods with ignorable assumptions is also discussed. Lastly, we stress the need for greater efforts in designing and monitoring clinical trials to prevent missing observations.

抄録全体を表示

PDF形式でダウンロード (155K)
討論の部

2006 年 27 巻 Special_Issue 号 p. S55-S61
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S55

ジャーナルフリー

PDF形式でダウンロード (109K)

話題3：Points to Consider on Multiplicity Issues in Clinical Trials

話題 3 : Points to Consider on Multiplicity Issues in Clinical Trialsに関する編集者のまとめ

臨床試験における多重性の問題についての留意点

森川敏彦

2006 年 27 巻 Special_Issue 号 p. S62-S63
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S62

ジャーナルフリー

PDF形式でダウンロード (98K)
Points to Consider on Multiplicity Issues in Clinical Trialsの内容紹介および問題提起

藤越慎治

2006 年 27 巻 Special_Issue 号 p. S64-S72
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S64

ジャーナルフリー

抄録を表示する抄録を非表示にする

“Points to Consider on Multiplicity Issues in Clinical Trials” published by CPMP of EMEA in September 2003 is reviewed and issues to be discussed are identified. First, the examples identified in the PtC as unnecessary cases of “adjusting the type I error level” are grouped into 3 patterns, and the situation and the characteristics of each pattern are explained. After reviewing each pattern, important points for conducting the confirmatory trial according to PtC are summarized. Issues to be discussed about the content and the concrete measures are also addressed.

抄録全体を表示

PDF形式でダウンロード (168K)
臨床評価における統計学上の論点：多重性の問題

渡邉裕之, 高橋健一

2006 年 27 巻 Special_Issue 号 p. S73-S77
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S73

ジャーナルフリー

抄録を表示する抄録を非表示にする

We would like to provide ideas about multiplicity from the practical point of view of a statistician in a pharmaceutical company. We think that a trial statistician should satisfy not only the requirements, described in ICH-E9, but should also be responsible for explaining statistical analyses, which may be complicated, to non-statisticians in simple language. In addition, certain multiple comparison methods that have been recently developed are hard to understand even for statisticians dealing with clinical trials. When these methods are applied to clinical trials, it is almost impossible to understand the essence of the multiple comparisons and interpret the results correctly. Therefore it is essential to plan a simple confirmatory clinical trial that can be interpreted clearly.

抄録全体を表示

PDF形式でダウンロード (136K)
臨床評価における統計学上の論点：医薬品の承認申請および審査における多重性の取り扱いについて

柴田大朗

2006 年 27 巻 Special_Issue 号 p. S78-S87
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S78

ジャーナルフリー

抄録を表示する抄録を非表示にする

In the development and regulatory review of pharmaceuticals, multiplicity is one of the important issues, and an adequate treatment of multiplicity is required by regulatory guidelines. Though the importance of statistically valid adjustment of multiplicity in drug development is nowadays well understood by practitioners, the more is required in the view of government agencies responsible for drug evaluation. To use the drug effectively and safely in clinical practice, not only the validity of the method itself, but also the validity of the formulation of clinical questions and the adequacy of the interpretation of results are required. In this article, two examples of new drug application review results, one by the US FDA and the other by the Japanese regulatory agency, are reviewed and discussed.

抄録全体を表示

PDF形式でダウンロード (178K)
討論の部

2006 年 27 巻 Special_Issue 号 p. S88-S93
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S88

ジャーナルフリー

PDF形式でダウンロード (91K)

話題4：Points to Consider on Switching between Superiority and Non-inferiority; Guideline on the Choice of Non-inferiority Margin

Points to Consider on Switching between Superiority and Non-inferiority; Guideline on the Choice of Non-inferiority Marginに関する編集者のまとめ

上坂浩之

2006 年 27 巻 Special_Issue 号 p. S94-S95
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S94

ジャーナルフリー

PDF形式でダウンロード (92K)
“Points to Consider on Switching between Superiority and Non-inferiority”及び “Guideline on the Choice of the Non-inferiority Margin”の紹介

西山智

2006 年 27 巻 Special_Issue 号 p. S96-S104
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S96

ジャーナルフリー

抄録を表示する抄録を非表示にする

This paper introduces the contents of two documents from the European authority, “Points to Consider on Switching between Superiority and Non-inferiority” and “Guideline on the Choice of the Non-inferiority Margin”. Issues relevant to possible applications in Japanese clinical trials are also discussed.

抄録全体を表示

PDF形式でダウンロード (267K)
Points to Consider on Switching between Superiority and Non-inferiority & Guideline on the Choice of Non-inferiority Marginへの討論

小山暢之

2006 年 27 巻 Special_Issue 号 p. S105-S115
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S105

ジャーナルフリー

抄録を表示する抄録を非表示にする

Two guidelines related to non-inferiority trials were released by the European Medicines Agency (EMEA). One pertains to the choice of non-inferiority margin and the other to switching the objective of a trial between superiority and non-inferiority. These guidelines describe principles for appropriately designing and interpreting non-inferior trials, but it is very difficult to follow these principles in an actual clinical trial setting. In this article, recommendations in interpreting these guidelines are discussed from a sponsor statisticians' point of view. Some issues of non-inferior trials not mentioned in these guidelines are also discussed.

抄録全体を表示

PDF形式でダウンロード (182K)
非劣性と優越性との交換と非劣性マージンの選択に関する統計的論点について

丹後俊郎

2006 年 27 巻 Special_Issue 号 p. S116-S119
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S116

ジャーナルフリー

抄録を表示する抄録を非表示にする

This short note discusses statistical issues in the appropriate design of randomized controlled trials with regards to the recent two documents, “Points to Consider on Switching between Superiority and Non-inferiority” and “Guideline on the Choice of the Non-inferiority Margin” from the European Agency for the Evaluation of Medicinal Products. This paper also points out the inappropriateness of the terminology of “superiority”defined in ICH E9 (Statistical Principles for Clinical Trials) and discusses its relationship with these matters.

抄録全体を表示

PDF形式でダウンロード (164K)
討論の部

2006 年 27 巻 Special_Issue 号 p. S120-S126
発行日: 2006/09/30
公開日: 2012/01/23

DOIhttps://doi.org/10.5691/jjb.27.S120

ジャーナルフリー

PDF形式でダウンロード (92K)

J-STAGEへの登録はこちら（無料）