Stratification of randomization is not required for a pre‐specified subgroup analysis

Published literature and regulatory agency guidance documents provide conflicting recommendations as to whether a pre‐specified subgroup analysis also requires for its validity that the study employ randomization that is stratified on subgroup membership. This is an important issue, as subgroup analyses are often required to demonstrate efficacy in the development of drugs with a companion diagnostic. Here, it is shown, for typical randomization methods, that the fraction of patients in the subgroup given experimental treatment matches, on average, the target fraction in the entire study. Also, mean covariate values are balanced, on average, between treatment arms in the subgroup, and it is argued that the variance in covariate imbalance between treatment arms in the subgroup is at worst only slightly increased versus a subgroup‐stratified randomization method. Finally, in an analysis of variance setting, a least‐squares treatment effect estimator within the subgroup is shown to be unbiased whether or not the randomization is stratified on subgroup membership. Thus, a requirement that a study be stratified on subgroup membership would place an artificial roadblock to innovation and the goals of personalized healthcare. Copyright © 2012 John Wiley & Sons, Ltd.     

Computation of the estimated parameters and wald statistic for the generalized growth curve model

Multivariate analysis is difficult when there are missing observations in the response vectors. Kleinbaum (1973) proposed a Wald statistic useful in the analysis of incomplete multivariate data. SUBROUTINE C0EF calculates the estimated parameter matrix g in the generalization of the Potthoff-Roy (1964) growth curve model proposed by Kleinbaum (1973). SUBROUTINE WALD calculates the Wald statistic for hypotheses of the form Hn: H 5 D = 0 as proposed by Kleinbaum (1973).     

Some properties of generalized ridge estimators

Exact expressions, in the form of infinite series expansions, are given for the first and second moments of two well known generalized ridge estimators. These series expansions are then evaluated using recursive formulas and computations are verified using approximations. Results are presented for the relative mean square error and bias of these estimators as well as their relative efficiency with respect to least squares.     

Limitations of the rank transform statistic in tests for interactions

Conover and Iman (1976), Iman (1974), and Iman and Conover (1976) have found the rank transform test to be robust and powerful when testing for interaction in experimental designs.The current study shows that, insofar as tests for interactions

are concerned, the rank transform test is robust and powerful in some circumstances but is dramatically nonrobust and manifests power significantly below that of the usual F test in some cases. Therefore, this procedure should be used only withcaution when employed in designs suchas those examined here.     

A bayesian analysis of the intraclass correlations in the mixed linear model

This article is concerned with the study of intraclass correlations in the mixed linear model. A brief account of the shortcomings of the existing meth¬ods (frequentist. likelihood and Bayesian) is followed by alternative Bayesian parametrizations involving intraclass correlations and variance ratios. Our prior specifications accommodate a priori dependencies as well as situations which involve little or no prior information. We give examples of interval estimation and hypothesis testing using data from an animal breeding study.     

Influence Analysis in Principal Component Analysis Through Power-Series Expansions

ABSTRACT

In influence analysis several problems arise in the field of Principal Components when applying different sample versions. Among these are the difficulty of determining a certain correspondence between the eigenvalues before and after the deletion of observations, the choice of the sign of the eigenvectors and the computational problem derived from the resolution of a great number of eigenproblems. In this article, such problems are discussed from the joint influence point of view and a solution is proposed by using approximations. Furthermore, the influence on a new parameter of interest is introduced: the proportion of variance explained by a set of principal components.     

Extensions of multiple linear regression

Many statistical methods are linked together through their connection with weighted least squares and hence regression. This article reviews these connections, emphasising the iteratively weighted least squares algorithm.     

Sample Size and Power Calculations for Left-Truncated Normal Distribution

Abstract

Sample size calculation is an important component in designing an experiment or a survey. In a wide variety of fields—including management science, insurance, and biological and medical science—truncated normal distributions are encountered in many applications. However, the sample size required for the left-truncated normal distribution has not been investigated, because the distribution of the sample mean from the left-truncated normal distribution is complex and difficult to obtain. This paper compares an ad hoc approach to two newly proposed methods based on the Central Limit Theorem and on a high degree saddlepoint approximation for calculating the required sample size with the prespecified power. As shown by use of simulations and an example of health insurance cost in China, the ad hoc approach underestimates the sample size required to achieve prespecified power. The method based on the high degree saddlepoint approximation provides valid sample size and power calculations, and it performs better than the Central Limit Theorem. When the sample size is not too small, the Central Limit Theorem also provides a valid, but relatively simple tool to approximate that sample size.     

A Note on Sample Size Determination for the Estimation of the Mean Vector of a Multivariate Population

In this article, we present a straightforward Bonferroni approach for determining sample size for estimating the mean vector of a multivariate population under two scenarios: (1) a pre-specified overall confidence level is desired; and (2) a pre-specified confidence level needs to be guaranteed for each individual variable. It is demonstrated that correlation between variables helps reduce the sample size. The formula to calculate the reduced sample size is derived. A binormal example is presented to illustrate the effect of correlation on sample size reduction for various values of the correlation coefficient.     

Monitoring Variation in a Multivariate Process When the Dimension is Large Relative to the Sample Size

A control procedure is presented for monitoring changes in variation for a multivariate normal process in a Phase II operation where the subgroup size, m, is less than p, the number of variates. The methodology is based on a form of Wilk' statistic, which can be expressed as a function of the ratio of the determinants of two separate estimates of the covariance matrix. One estimate is based on the historical data set from Phase I and the other is based on an augmented data set including new data obtained in Phase II. The proposed statistic is shown to be distributed as the product of independent beta distributions that can be approximated using either a chi-square or F-distribution. An ARL study of the statistic is presented for a range of conditions for the population covariance matrix. Cases are considered where a p-variate process is being monitored using a sample of m observations per subgroup and m < p. Data from an industrial multivariate process is used to illustrate the proposed technique.