Estimation Bias in Complete-Case Analysis in Crossover Studies with Missing Data

Crossover designs are used often in clinical trials. It is not uncommon that subjects discontinue before completing all treatment periods in a crossover study. Despite availability of statistical methodologies utilizing all available data and software for obtaining valid inferences under the assumption of missing at random (MAR), naïve approaches, such as the complete case (CC) analysis, which is only valid with a strong assumption of missing completely at random are still widely used in practice. In this article, we obtain the analytical form of the estimation bias of treatment effects with CC for linear mixed models. We use simulation studies to examine the inflation of Type I error and efficiency loss in the inferences with CC under MAR. Invalidity and inefficiency of two other commonly used approaches for defining analyzed data in the presence of missing data, including data from at least two periods in three period crossover and available cases for a specific comparison of interest, are also demonstrated through simulation studies.     

On asymptotic non-normality of null distributions of mrpp statistics

Severe departures from normality occur frequently for null distributions of statistics associated with applications of mulLi-response permutation procedures (MRPP) for either small or large finite populations. This paper describes the commonly encountered situation associated with asymptotic non-normality for null distributions of MRPP statistics which does not depend on the underlying multivariate distribution. In addition, this paper establishes the existence of a non-degenerate underlying distribution for which the null distributions of MRPP statistics are asymptotically non-normal for essentially all size structure configurations. It is known that MRPP statistics are symmetric versions of a broader class of statistics, most of which are asymmetric. Because of the non-normality associated with null distributions of MRPP statistics, this paper includes necessary results for inferences based on the exact first three moments of anv statistic in this broader class (analogous to existing results for MRPP statistics).     

Univaiuate anu multivariate categorical data analysis for block designs

Analysis for univariate and multivariate categorical data in block designs is given and illustrated through examples. The univariate analysis compares the treatments on the basis of their pooled frequency distributions (pooled over blocks). The test statistic used is called Q after Cochran (1950). The large sample null distribution of Q is a chi-square. Analysis of p-variate categorical data (kth variable having ck classes, K=1,...,p) can be done by treating it as a univariate categorical problem with [d] classes. Very often [d] is large in relation to the size of the experiment. This makes the expected frequencies for some of the cells very small, making the univariate method inapplicable. In these circumstances it may be reasonable to compare the treatments on the basis of marginal distributions up to the mth dimension, 1[d] , which is given in this paper. This method is also illustrated for missing observations     

Response predictions in regressions on panel data

In this paper we consider the problem of obtaining best linear unbiased estimators of individual response coefficients in a Random Coefficient Linear Regression (RCR} Model, comparing alternative estimators for these response vectors through a simulation study. We also provide an empirical example that illustrates the estimation procedure proposed here.     

Using the singly truncated normal distribution to analyze satellite data

This paper proposes the singly truncated normal distribution as a model for estimating radiance measurements from satellite-borne infrared sensors. These measurements are made in order to estimate sea surface temperatures which can be related to radiances. Maximum likelihood estimation is used to provide estimates for the unknown parameters. In particular, a procedure is described for estimating clear radiances in the presence of clouds and the Kolmogorov-Smirnov statistic is used to test goodness-of-fit of the measurements to the singly truncated normal distribution. Tables of quantile values of the Kolmogorov-Smirnov statistic for several values of the truncation point are generated from Monie Carlo experiment Mnally a numerical emample using satetic data is presented to illustrate the application of the procedures.     

Nonparametric prediction analysis for binary data

A nonparametric inference algorithm developed by Davis and Geman (1983) is extended problem. The algorithm and applied to a medical prediction employs an estimation procedure for acquiring pairwise statistics among variables of a binary data set, allows for the data-driven creation of interaction terms among the variables, and employs a decision rule which asymptotically gives the minimum expected error. The inference procedure was designed for large data sets but has been extended via the method of cross-validation to encompass smaller data sets.     

Comparison of tests for bivariate symmetry versus location and/or scale alternatives

This paper studies the performance of tests which use a null hypothesis of bivariate symmetry and detect the broad class of location and/or scale alternatives . The conditionally distribution-free tests of Sen (1967) and Hollander (1971) and parametric tests related to those of Bell and Haller (1969) are compared in a Monte Carlo study which also includes a new conditionally distribution-free test.     

Practical bayesian approaches to the analystcs of a 2×2 contingency table with incompletely categorized data

To assess the efficacy of a treatment, patients are administered a pre-test, the treatment, and a post-test (identical to the pre-test). These patients are then categorized according to their outcomes observed on both tests,e.g., (S,S), (S,F), etc. Also, we observe "incomplete" information on the pre-tests' outcomes for some patients and the results of only the post-test being known for thers, A Bayesian framework is fit to the problem and Bayes factors, posterior odds ratios, and utility functions are given to evaluate th e treatment, A method of assessing the prior distribution is specified and a numerical example is worked.     

More flexible sequential and non-sequential designs in long-term clinical trial

In this paper, we describe decision making procedures as they exist in most clinical trials,review some recently suggested approaches to monitoring and clarify how these methods allow greater flexibility in monitoring and explicit specification of data monitoring methods in the protocol.