著者

三輪 哲久

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.29, no.Special_Issue_1, pp.S5-S14, 2008-07-01 (Released:2011-12-02)

参考文献数

14

被引用文献数

3 1

---

It is common in statistical analyses to perform two or more tests for a set of data. Then the problem of multiplicity arises. This article concisely describes the basic principles of multiple test procedures. Three fundamental methods for controlling the family-wise type I error rates are explained in a unified manner: 1) Bonferroni procedure, 2) simultaneous confidence intervals, 3) closed testing procedure.

著者

寒水 孝司

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.36, no.Special_Issue_2, pp.S87-S98, 2015-11-30 (Released:2016-01-15)

参考文献数

33

---

Clinical trials often involve multiple objectives related to multiple settings such as treatment arms, endpoints (primary, secondary, or tertiary), and subgroups. In such clinical trials, multiplicity issues caused by multiple statistical tests need to be adequately handled throughout studies. Novel statistical methods to account for several sources of multiplicity have been developed and applied in recent clinical trials. This article briefly reviews and summarizes the multiplicity issues in clinical trials that have multiple objectives and discusses the considerations in trial design, analysis, data interpretation, and the reporting of results. Relevant textbooks, articles, an international conference, guidances, and a web site are provided as references.

著者

Tasuku Okui Yutaka Matsuyama Shigeyuki Nakaji

出版者

The Biometric Society of Japan

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.39, no.2, pp.55-84, 2019-01-31 (Released:2019-05-11)

参考文献数

59

---

Nowadays, many methods that employ the 16S ribosomal RNA gene (16S rRNA sequencing data) have been proposed for the analysis of gut microbial compositional data. 16S rRNA sequencing data is statistically multivariate count data. When multivariate data analysis methods are used for association analysis with a disease, 16S rRNA sequencing data is generally normalized before analysis models are fitted, because the total sequence read counts of the subjects are different. However, proper methods for normalization have not yet been discussed or proposed. Rarefying is one such normalization method that equals the total counts of subjects by subsampling a certain amount of counts from each subject. It was thought that if rarefying were combined with ensemble learning, performance improvement could be achieved. Then, we proposed an association analysis method by combining rarefying with ensemble learning and evaluated its performance by simulation experiment using several multivariate data analysis methods. The proposed method showed superior performance compared with other analysis methods, with regard to the identification ability of response-associated variables and the classification ability of a response variable. We also used each evaluated method to analyze the gut microbial data of Japanese people, and then compared these results.

著者

奥井 佑 中路 重之

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.39, no.1, pp.37-54, 2018-08-01 (Released:2019-04-04)

参考文献数

32

---

In recent years, analysis methods of microbiome data are developing rapidly, and many methods for the microbial compositional data which uses the 16S ribosomal RNA gene (16S rRNA data) are proposed. But, methods of association analysis for longitudinally measured 16S rRNA data are not studied well. Latent dirichlet allocation model (LDA) which is used mainly in natural language processing and has high expansion possibilities came to be applied to 16S rRNA data analysis in the past few years. Then, we propose an association analysis method by modifying existing LDA: topic tracking model for longitudinal 16S rRNA data. As the result of predictive performance evaluation, proposed method showed superior performance compared with topic tracking model with regard to perplexity. We applied this method to microbial data of rural Japanese people and identified topics associated with obesity.

著者

清見 文明

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.24, no.2, pp.95-115, 2004-03-12 (Released:2012-02-23)

参考文献数

36

---

In randomized clinical trials, last observation or change from baseline (last observation-baseline) is frequently adopted as an endpoint. In two-arm comparison trials in Japan, a two-sample t-test is often employed in the primary analysis whereas an analysis of covariance (ANCOVA) with baseline covariate assuming equal slopes between the groups is seldom employed. This paper discusses the adoption of the ANCOVA as the primary analysis and recommends its use provided that the assumptions for ANCOVA are satisfied. First, the powers of the t-test and the ANCOVA are presented in order to investigate the extent of how the ANCOVA can increase power. Next, several reasons for not employing the ANCOVA are discussed. Percentage change is also briefly discussed.The power of the ANCOVA with baseline covariate is dependent on the correlation coefficient between baseline and last observation, and on the magnitude relation of variances of baseline and last observation. This paper presents several factors that are responsible for reducing the correlation coefficient and several factors which influence the magnitude relation.

著者

柴田 大朗

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.27, no.Special_Issue, pp.S78-S87, 2006-09-30 (Released:2012-01-23)

参考文献数

15

---

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.

著者

田中 司朗 大庭 幸治 吉村 健一 手良向 聡

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.31, no.1, pp.23-48, 2010-07-31 (Released:2010-12-14)

参考文献数

71

被引用文献数

1 1

---

Surrogate endpoints, which represent a compromise in the conflict between measurability and clinical relevance of endpoints, have considerable advantage in rapid drug approvals compared to true endpoints in confirmatory clinical trials dealing with life-threatening diseases, such as cancer or AIDS. However, past experiences have shown the risk of relying too heavily on surrogate endpoints. In this paper, we review statistical criteria for evaluating surrogate endpoints and the past examples properly evaluated the surrogacy, taking into consideration relevant clinical and statistical issues.

著者

大門 貴志

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.33, no.1, pp.1-29, 2012-08-31 (Released:2012-10-02)

参考文献数

145

被引用文献数

2

---

A number of designs of phase I dose-finding trials have been developed. Algorithm-based designs such as standard 3 + 3 designs are easy to understand and implement since they do not require explicit model specification for a dose-toxicity relationship. On the other hand, model-based designs such as the continual reassessment method (CRM) (O’Quigley et al., 1990) have been proposed. The author will give a review of the CRM and its related topics. In particular, the author makes mention of some of the problems with 3 + 3 designs that have often been used in phase I dose-finding studies and gives a detailed description of ideas, concepts, theories, properties and issues in the CRM.

著者

猪川 和朗 田中 潤

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.36, no.Special_Issue, pp.S3-S18, 2015-06-30 (Released:2015-09-08)

参考文献数

10

被引用文献数

1

---

We describe fundamental knowledge of pharmacokinetics analysis for phase I trials, particularly focusing on basic parameters (such as bioavailability, volume of distribution, fraction unbound, clearance), estimation and analysis methods (such as compartmental and non-compartmental), points to consider (such as steady state and dose proportionality). The NCA is an abbreviation for Non Compartmental Analysis, and the meaning is pharmacokinetic analysis without pharmacokinetic model. There is something that we should consider in NCA such as AUC calculation method, handling method of not detectable concentrations, point selection for λz calculation, and selection of sampling time. Steady state occurs when the overall intake of a drug is equilibrium with its elimination. At steady state the mean plasma concentrations of the drug are similar by any dosing interval. In practice, it is generally considered that steady state is reached when a time of 5 times the half-life for a drug. For the dose proportionality, the measures of exposure, such as maximal blood concentration (Cmax), area under the curve from 0 to infinity (AUC), are proportional to the dose. The three methods, Analysis of variance of the PK response, normalized by dose, linear regression and power model, are used to assess dose proportionality.

著者

西 次男

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.27, no.1, pp.69-79, 2006-06-30 (Released:2011-09-25)

参考文献数

9

---

We showed a dynamic allocation procedure to achieve a specified proportion of sample sizes among treatment groups not only within all patients, but also within patients with strata composed of centers and/or prognostic factors in randomized controlled clinical trials. This procedure allocates a patient to one of treatment groups that are within a pre-specified range from the best balance, as well as the treatment groups with the best balance. When target sample sizes of two treatment groups are the same, Zelen (1974) showed a restriction for a range of obtained sample sizes. Proposed method is an extension of Zelen's restriction to the case of different target sample sizes of more than two treatment groups. This method can introduce randomness into a dynamic allocation procedure keeping comparability among treatment groups.

著者

津本 周作 平野 章二 津本 優子

出版者

The Biometric Society of Japan

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.29, pp.S155-S176, 2008-12-15

被引用文献数

1

---

Hosptial information system (HIS) collects all the data from all the branches of departments in a hospital, including laboratory tests, physiological tests, electronic patient records. Thus, HIS can be viewed as a large heterogenous database, which stores chronological changes in patients' status. This paper overviews three applications of data mining and statistical methods to HIS. First, clustering of temporal sequences based on multiscale matching was applied for grouping chronic hepatitis. Second, decision tree method was used for detection of risk factors, which was successfully used to prevent nursing medication errors. Finally, several linear models were applied for hospital management data. These results show that data mining methods, including decision tree mining, temporal data mining, are useful for detection of risk factors from large distributed data such as HIS, whose process can be called risk mining.

著者

佐藤 俊哉

出版者

日本計量生物学会

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.28, no.Special_Issue_1, pp.S57-S62, 2007-10-01 (Released:2011-09-25)

参考文献数

17

---

In this paper, I will review recent development in epidemiologic theories. It is emphasized that case-control studies are considered to be based on a underlying hypothesized cohort. Thus, various control selection options have been developed as the selection from the population at risk in that hypothesized cohort.As an example of the use of new epidemiologic designs, a case-control study of infant asthma is illustrated. It is a part of the SORA (Study on Respiratory Disease and Automobile Exhaust) project which is a complex of epidemiologic studies for infants, school children, and adults conducted by the Ministry of the Environment. In that study, a two-stage case-control design which is effcient both for rare exposure and rare disease is adopted.