Control of type 1 error in a hybrid complete two‐period vaccine efficacy trial

A complete two‐period experimental design has been defined as one in which subjects are randomized to treatment, observed for the occurrence of an event of interest, re‐randomized, and observed again for the event in a second period. A 4‐year vaccine efficacy trial was planned to compare a high‐dose vaccine with a standard dose vaccine. Subjects would be randomized each year, and subjects who had participated in a previous year would be allowed to re‐enroll in a subsequent year and would be re‐randomized. A question of interest is whether positive correlation between observations on subjects who re‐enrolled would inflate the variance of test statistics. The effect of re‐enrollment and correlation on type 1 error in a 4‐year trial is investigated by simulation. As conducted, the trial met its power requirements after two years. Subjects therefore included some who participated for a single year and others who participated in both years. Those who participated in both years constituted a complete two‐period design. An algebraic expression for the variance of the treatment difference in a complete two‐period design is derived. It is shown that under a ‘no difference’ null, correlation does not result in variance inflation in this design. When there is a treatment difference, there is variance inflation but it is small. In the vaccine efficacy trial, the effect of correlation on the statistical inference was negligible. Copyright © 2014 John Wiley & Sons, Ltd.     

Asymptotic normality of numbers of observations in random regions determined by order statistics

In this paper, we study the joint limiting behaviour of numbers of observations that fall into regions determined by order statistics and Borel sets. We show that suitably centred and normed versions of these numbers are asymptotically multivariate normal under some conditions. We consider two cases: one where the population distribution function is discontinuous and the other where it is continuous and the order statistics are extreme. Finally, we compare results obtained for the two cases with their analogues for absolutely continuous distribution function and central-order statistics.     

Minimal circular balanced repeated measurement designs in unequal period sizes

Abstract

Repeated measurement designs (RMDs) are widely used in medicine, pharmacology, animal sciences and psychology. In these fields, there are several situations where these designs should be used in periods of different sizes. With the use of RMD, residual effects or carry over effects may arise and balanced RMDs are solution to this problem. In this article, therefore, some infinite series are developed through method of cyclic shifts to obtain circular balanced repeated measurements designs in periods of two different sizes.     

Maximum likelihood estimates in the multivariate normal with patterned mean and covariance via the em algorithm

The maximum likelihood equations for a multivariate normal model with structured mean and structured covariance matrix may not have an explicit solution. In some cases the model's error term may be decomposed as the sum of two independent error terms, each having a patterned covariance matrix, such that if one of the unobservable error terms is artificially treated as "missing data", the EM algorithm can be used to compute the maximum likelihood estimates for the original problem. Some decompositions produce likelihood equations which do not have an explicit solution at each iteration of the EM algorithm, but within-iteration explicit solutions are shown for two general classes of models including covariance component models used for analysis of longitudinal data.     

A bayesian approach to detect informative observations in an experiment

In this article Lindley's (1956) measure of average information is used to measure the loss of information due to the unavailability of a set of observations in an experiment. This measure of loss of information may be used to detect a set of most informative observations in a given design.     

On the information content of partial observations

The modified zero order approach to estimating coefficients in the face of missing observations treats them as parameters to be estimated simultaneously with the missing observations. The paper then investigates (in the context of Han's generalized regression model)(i) when parameter estimators don't vary between using the partial data points and using only the complete ones (the informationless result), and (ii) large sample properties of the modified zero order estimator. It's found the sequential cut property is crucial to the informationless result for coefficient estimators; consistency of the modified zero order estimator depends on the percentage of observations with missing elements for large sample sizes or the sequential cut property.     

The influence of observations on misclassification probability in multiple discriminant analysis

The influence of observations in estimating the misclassification probability in multiple discriminant analysis is studied using the common omission approach. An empirical influence function for the misclassification probability is also derived, It can give a very good approximation to the omission approach, but the computational load is much reduced, Various extensions of the measures are suggested. The proposed measures are applied to the famous Iris data set. The same three observations are identified as having the most influence under different measures.