著者

平川 晃弘 浅野 淳一 佐藤 宏征 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.39, no.2, pp.85-101, 2019-01-31 (Released:2019-05-11)

参考文献数

62

被引用文献数

1 1

---

In oncology, next generation sequencing and comprehensive genomic profiling have enabled detailed classification of tumors using molecular biology. It, however, may be unrealistic to conduct phase I-III trials according to each subpopulation based on the molecular subtypes. Common protocols that assess the combination of several molecular markers and their targeted therapies by means of multiple sub-trials are required. These protocols are called “master protocols,” and are drawing attention as a next-generation clinical trial design. In this review, we provide an overview of clinical trials based on master protocol including basket, umbrella, and platform trials along with their recent examples. We also discuss the statistical challenges encountered in their application.

著者

川口 淳

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.2, pp.145-174, 2013-02-28 (Released:2013-03-07)

参考文献数

116

被引用文献数

2

---

Imaging techniques have been used for effectively studying the brain in a non-invasive manner in several fields, for example, psychiatry and psychology. In this review, we focus on two imaging techniques that provide different views of brain structure and function. Structural magnetic resonance imaging (sMRI) provides information about various tissue types in the brain, for example, gray matter, white matter, and cerebrospinal fluid. Functional MRI (fMRI) measures brain activity by detecting changes in cerebral blood flow. These techniques enable high-quality visualization of brain activity or the location of atrophies; moreover, these techniques facilitate the study of disease mechanisms in the healthy brain and might lead to the development of effective therapies or drugs against such diseases. However, raw MRI data must be statistically analyzed to obtain objective answers to clinical questions. Therefore, statistical methods play a very important role in brain research. Here, we briefly review the most commonly used statistical analyses, namely, data pre-processing, general linear model, random field theory, mixed effect model, independent component analysis, network analysis, and discriminant analysis. Further, we provide information about brain imaging data structure and introduce useful software to implement these methods.

著者

鵜飼 保雄

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.32, no.Special_Issue, pp.S1-S17, 2011-05-31 (Released:2011-09-05)

参考文献数

15

著者

野村 尚吾 大東 智洋 澤本 涼

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.43, no.1, pp.63-96, 2022 (Released:2023-03-24)

参考文献数

57

---

International momentum to promote the use of external control data in clinical trials is growing. The use of external control data to augment the control arm in randomized controlled trials (RCTs), termed as a hybrid control approach, is one of the most attracting areas for actual applications. In this article, we focus on a situation where an endpoint of interest is binary and the summary statistics of external control are available to this end. The purpose is to review design and analysis methods for RCTs incorporating a hybrid control approach. The methods of interests are test-then-pool, power prior and its extended versions, Pocock’s method, commensurate prior, meta-analytic predictive prior and its robustified version, unit-information prior, elastic prior, and so on. For better understanding of Bayesian methods, a brief overview of recent proposals regarding an effective sample size is also presented. Most of these methods are applied to an actual placebo-controlled RCT for ankylosing spondylitis patients which applied a hybrid control approach by using summary statistics of past RCTs.

著者

西川 正子

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.2, pp.141-170, 2008-12-01 (Released:2011-09-15)

参考文献数

73

被引用文献数

2 1

---

The statistical analysis of survival time or failure time data is an important topic in many areas of research. In ordinary survival data, there is a single, possibly right-censored failure time for each individual. However, in a number of medical applications whereby data is collected an individual may experience one or more events but the first event will preclude the occurrence of another event under investigation. As a result, he/she can experience only one of several types of events. Such data are commonly referred to as competing risks data. Censoring due to such an event is generally not independent of the time to the event of interest.This paper reviews statistical methods for analyzing a competing risks model. Both conceptual considerations and common approaches to one-sample inference; two sample comparison; and covariate effect modeling are discussed. The theory for the analysis of ordinary right-censored survival data can be applied under certain circumstances. Standard statistical software package can perform the necessary analysis, although interpretation of results will vary.

著者

吉村 功 椿 広計 佐藤 喬俊 厳 浩 山本 精一郎 森田 智視 船渡川 伊久子 柴田 大朗 伊藤 陽一 松山 裕

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.42, no.1, pp.1-13, 2021 (Released:2022-04-22)

著者

中村 理恵 野間 久史

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.41, no.2, pp.117-136, 2021 (Released:2021-05-11)

参考文献数

31

---

In multicenter clinical trials, the assessment for heterogeneity of various relevant factors across participating centers is a relevant issue because it can cause inconsistency of the treatment effects. Especially, outlying centers with extreme profiles can influence the overall conclusions of these trials. In this article, we propose quantitative methods to detect the outlying centers and to assess their influences in multicenter clinical trials. We proposed four effective methods based on (1) a studentized residual obtained by a leave-one-out analysis, (2) a model-based significance test to detect an outlying trial using a mean-shifted model, (3) a relative change measure for the variance estimate of the overall treatment effect estimator, and (4) a relative change measure for the heterogeneity variance estimate in a random-effects model. In addition, we provide parametric bootstrap algorithms to assess the statistical variability of their influential measures. We also demonstrate the practical effectiveness of these proposed methods via applications to two clinical trials for benign prostatic hyperplasia and cardiovascular heart disease.

著者

関山 英孝 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.37, no.2, pp.89-100, 2016-12-31 (Released:2017-05-16)

参考文献数

11

被引用文献数

2 3

---

The Japanese Adverse Drug Event Report (JADER) database of the Pharmaceutical and Medical Devices Agency (PMDA) has been available to the public since 2012. The database includes reports on drug-related adverse events from pharmaceutical companies or medical institutions. It is expected to improve the proper use of pharmaceutical products through pharmacoepidemiological studies using the JADER. However, wrong results and interpretations would be derived unless the features of JADER are carefully considered before the study. However, no study has investigated JADER from the viewpoint of data cleaning.Herein, we summarized the features and precautions for use of JADER (downloaded on June 2015). For example, we found many misspellings and drug names input in various forms because of incorrect Japanese Kanji, voiced and semi-voiced dots, and half-width and full-width forms. We also found that the number of adverse events tends to increase throughout the year, with the highest number reported in the third quarter (October-December). Finally, emergency or rapid safety information (i.e., yellow letter and blue letter) and results of drug use surveys generally increase the number of adverse events reported in JADER.

著者

佐藤 恵子 岩崎 学 菅波 秀規 佐藤 俊哉 椿 広計

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.35, no.1, pp.37-53, 2014-08-31 (Released:2014-10-15)

参考文献数

18

被引用文献数

1 1

---

All statisticians are expected to produce statistical outcomes of high quality and reliability. To ensure reliability in statistical performance and outcomes and to meet societal expectations, certain standards of conduct (SOC) must be established such that individual statisticians embrace their own principles and so that the community of statisticians as a whole functions with more self-control.In 2008, the Biometric Society of Japan began revision of the code of conduct, and the working group drafted an SOC. This particular draft re.ected the opinions of statisticians and the basic concepts which aligned well with ethical guidelines of the American Statistical Association and the International Statistical Institute. As forced guidelines rarely result in full compliance and increased ethical conduct, the SOC offers a framework to encourage individual biostatisticians to establish and hold their own principles and to act responsibly with integrity.The SOC comprises a preamble, mission statement, values, ten principles and background information. The draft SOC was approved by the Council of the Biometric Society of Japan in November 2013.The SOC will help statisticians improve their capacity to perform sound statistical practices, improve the working environment, cultivate the next generation of statisticians with professionalism, and acquire societal trust.

著者

森川 敏彦

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.S15-S32, 2008-07-01 (Released:2011-12-02)

参考文献数

25

被引用文献数

4 3

---

This paper discusses various multiplicity issues arisen in clinical trials and possible statistical approaches to these issues. We especially stress the importance of the closed testing procedures (CTPs) in the setting of clinical trials: They include various modified Bonferroni procedures, e.g., step-down Dunnett procedure, hierarchical procedure, and Williams test. Moreover they can be even applied to adaptive designs in clinical trials. We illustrate the basic CTP procedures in detail.

著者

渡橋 靖

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.S61-S68, 2008-07-01 (Released:2011-12-02)

参考文献数

20

---

The ICH E14 guideline provides recommendation to assess QT interval prolongation and proarrhythmic potential of non-antiarrhythmic drugs in clinical studies. As there exist many statistical issues in the clinical evaluation of QT prolongation, electrocardiograms, background information of the guideline and QT interval correction methods are described for introduction. Because of the inverse relationship to heart rates, QT intervals are corrected for heart rates in order to obtain a variable which is independent of heart rate. Population-derived correction, subject-specific correction, and other correction methods are introduced. Assumptions of each correction method and its properties are discussed. Study design should be considered to collect appropriate data and estimate accurate heart rate correction formulae.

著者

寒水 孝司 武蔵 優希 中山 拓人

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.38, no.2, pp.141-152, 2018 (Released:2018-05-18)

参考文献数

15

被引用文献数

1

---

The American Statistical Association released a “Statement on Statistical Significance and P-Values.” There has been extensive global discussion on p-values since their use was introduced. It is necessary to eliminate or reduce significance chasing, and misin-terpretation and misuse of p-values while incorporating their proper use. This article discusses the possible causes of such problems by examining statistics education at schools of medicine, dentistry and pharmaceutical sciences in Japanese universities. In the first part of the article, we discuss the implications of the model core curricu-lum for each educational field and the reference standards of educational policy in statistics, and in the second part, we discuss the implications of the survey results for introductory statistics courses at schools of medicine, dentistry, and pharmaceutical sciences. The surveys collected relevant data from online syllabi of statistics courses along with researchers’ information published on university websites. The survey items introduced in this article include the course names, textbooks, doctoral subject and employment status of each lecturer, and course contents.

著者

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.29, no.2, pp.111-124, 2008-12-01 (Released:2011-09-15)

参考文献数

32

---

The aim of single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase exploratory trials or proof-of-concept studies as they take into account information that accrues during a trial. Posterior and predictive probabilities are then updated and so become more accurate as the trial progresses. If the relevant external information is available, the decision will be made with a smaller sample size. The goal of this paper is to provide a review for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, a clinical trial is presented as a real example to illustrate how to conduct a Bayesian approach for single-arm clinical trials with binary endpoints.

著者

丹後 俊郎

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.S116-S119, 2006-09-30 (Released:2012-01-23)

参考文献数

1

---

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.

著者

松井 茂之

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.38, no.2, pp.127-139, 2018-03-01 (Released:2018-05-18)

参考文献数

32

---

In this article, we discuss the role of P values in multiple testing to associate a large number of genetic or molecular features with a phenotypic variable of interest in biomedical omics studies. For multiple tests in such association analyses, we distinguish those conducted for confirmatory purpose, as seen in genome-wide association studies to determine disease-associated variants, from those for exploratory screening of associated features. For the latter, exploratory analysis, we discuss application of the ROC curve analysis used in diagnostic medicine, as an alternative, but more relevant framework, rather than the standard framework based on multiple testing that controls false positives only. Finally, partly based on arguments made in the field of omics studies, we make some comments on future endeavors by statisticians to disseminate discussions given in the ASA’s Statement on P-Values (Wasserstein and Lazar, 2016, The American Statistician, 70, 129-133) to improve statistical practice in various scientific fields.

著者

手良向 聡

出版者

The Biometric Society of Japan

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.44, no.1, pp.35-51, 2023-10-31 (Released:2023-12-06)

参考文献数

51

---

Determination of the number of subjects to include in a clinical trial is a crucial aspect of experimental design. The standard methodology for sample size determination (SSD) has been established based on a frequentist perspective, while the literature addressing the SSD problem from a Bayesian perspective has increased for the last 20 years. In this paper I discuss the basic concept of Bayesian SSD, with specific focus on an inferential performance-based (non-decision theoretic) approach, using two distinct prior distributions: analysis prior and design prior. The analysis prior formalizes pre-trial information, and it is used to obtain posterior distributions, while the design prior describes a scenario and it is used to obtain prior predictive distributions. In practice, the specification of prior distributions is a key element of Bayesian inference. The prior information may be derived from either expert beliefs or relevant empirical data, and the subjective knowledge derived from an expert elicitation procedure may be useful to define a prior distribution when no or limited data from previous studies is available. In experimental design, the interplay between Bayesian and frequentist methodology is intrinsic. Whichever method is used in SSD, the distinction between demands as expressed in the range of equivalence, and their expectation or beliefs, as represented by the prior information is of paramount importance.

著者

三中 信宏

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.S25-S34, 2007-10-01 (Released:2011-09-25)

参考文献数

37

---

Contemporary evolutionary biology has used various statistical methods for collecting and analyzing data. Here methods for estimating phylogenetic trees are reviewed in the context of recent history of evolutionary biology, especially of systematics and phylogenetics. Estimating evolutionary history based on character data (molecular or morphological) poses a couple of epistemological problems all of which are common to historical sciences in general. Karl Popper's philosophy of science, in particular, his theory of falsification and corroboration has been espoused by many theoretical phylogeneticists. In this paper the long-standing controversy on philosophical aspects of phylogenetics and its implications for statistical methods in this discipline is discussed.

著者

船渡川 伊久子 船渡川 隆

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.S33-S48, 2015-06-30 (Released:2015-09-08)

参考文献数

42

---

Longitudinal data are data collected repeatedly from each subject for a particular response variable over a certain time period. Specifically, in longitudinal data analysis, the researchers are interested in changes in the response levels over time and the differences in these changes among factor levels or covariates. Because of within-subject correlations, analysis methods considering the correlations or variance-covariance structures have been developed. One of the approaches is the use of mixed effects models that take into account between-subject heterogeneity by random effects. In population pharmacokinetics, the response variable corresponds to drug concentration and is analysed typically using nonlinear mixed effects models. In this article, longitudinal data analysis with a continuous response variable is introduced focusing on population pharmacokinetics. Longitudinal data analysis, linear mixed effects models, nonlinear mixed effects models, and population pharmacokinetics are discussed from a biostatistical point of view. This article is expected to be of interest to biostatisticians, pharmacologists, pharmacokineticists, and those in related fields.

著者

橋本 敏夫 山田 雅之 笠井 英史

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.S19-S31, 2015-06-30 (Released:2015-09-08)

参考文献数

14

被引用文献数

3

---

This paper reviews the statistical aspects in pharmacokinetic analysis of clinical Phase 1 trials. Based on the understanding that most pharmacokinetic parameters follow a lognormal distribution, it is considered to be appropriate to summarize them by the geometric mean, geometric CV or geometric SD. Then we conducted simulation studies of a pharmacokinetic model to investigate whether pharmacokinetic parameters follow a lognormal distribution. Using numerical examples obtained by the simulation, we described in detail how to display the summary statistics of pharmacokinetic parameters. We also indicated that geometric mean is also useful to summarize the plasma concentration, and that the concetration below the lower limit of quantification shoud be carefully handled.

著者

Takashi Yanagawa

出版者

The Biometric Society of Japan

雑誌

計量生物学 (ISSN:09184430)

巻号頁・発行日

vol.40, no.2, pp.69-79, 2020-06-01 (Released:2020-07-21)

参考文献数

15

---

Reproducibility is the essence of a scientific research. Focusing on two-sample problems we discuss in this paper the reproducibility of statistical test results based on p-values. First, demonstrating large variability of p-values it is shown that p-values lack the reproducibility, in particular, if sample sizes are not enough. Second, a sample size formula is developed to assure the reproducibility probability of p-value at given level by assuming normal distributions with known variance. Finally, the sample size formula for the reproducibility in general framework is shown equivalent to the sample size formula that has been developed in the Neyman-Pearson type testing statistical hypothesis by employing the level of significance and size of power.