Modelling paired categorical outcomes in clinical trials

The goal of this paper is to discuss methods for testing the homogeneity of treatment‐induced changes in trials with paired categorical responses. Widely used marginal homogeneity tests ignore the information contained in concordant pairs of observations and become highly underpowered for configurations of parameters encountered in real trials. This paper considers models for paired binary or ordinal outcomes based on both discordant and concordant pairs that provide a natural extension of marginal models. Likelihood‐ratio tests associated with these models are developed and are demonstrated to be at least as powerful as or more powerful than marginal homogeneity tests. The proposed models are easy to fit using standard statistical software. Copyright © 2003 John Wiley & Sons, Ltd.     

Marginal inhomogeneity models for square contingency tables with nominal categories

For the analysis of square contingency tables with nominal categories, this paper proposes two kinds of models that indicate the structure of marginal inhomogeneity. One model states that the absolute values of log odds of the row marginal probability to the corresponding column marginal probability for each category i are constant for every i. The other model states that, on the condition that an observation falls in one of the off-diagonal cells in the square table, the absolute values of log odds of the conditional row marginal probability to the corresponding conditional column marginal probability for each category i are constant for every i. These models are used when the marginal homogeneity model does not hold, and the values of parameters in the models are useful for seeing the degree of departure from marginal homogeneity for the data on a nominal scale. Examples are given.     

Homogeneity Test of Risk Differences of Marginal and Conditional Probabilities in Several Incomplete Correlated 2 × 2 Tables

This article considers K pairs of incomplete correlated 2 × 2 tables in which the interesting measurement is the risk difference between marginal and conditional probabilities. A Wald-type statistic and a score-type statistic are presented to test the homogeneity hypothesis about risk differences across strata. Powers and sample size formulae based on the above two statistics are deduced. Figures about sample size against risk difference (or marginal probability) are given. A real example is used to illustrate the proposed methods.     

Tests of marginal homogeneity and special cases

The analysis of two‐way contingency tables is common in clinical studies. In addition to summary counts and percentages, statistical tests or summary measures are often desired. If the data can be viewed as two categorical measurements on the same experimental unit (matched pair data) then a test of marginal homogeneity may be appropriate. The most common clinical example is the so called ‘shift table’ whereby a quantity is tested for change between two time points. The two principal marginal homogeneity tests are the Stuart Maxwell and Bhapkar tests. At present, SAS software does not compute either test directly (for tables with more than two categories) and a programmatic solution is required. Two examples of programmatic SAS code are found in the current literature. Although accurate in most instances, they fail to produce output for certain tables (‘special cases’). After summarizing the mathematics behind the two tests, a SAS macro is presented, which produces correct output for all tables. Finally, several examples are coded and presented with resultant output. Copyright © 2013 John Wiley & Sons, Ltd.     

Measure of departure from conditional marginal homogeneity for square contingency tables with ordered categories

For the analysis of square contingency tables with ordered categories, Tomizawa et al. (S. Tomizawa, N. Miyamoto, and N. Ashihara, Measure of departure from marginal homogeneity for square contingency tables having ordered categories, Behaviormetrika 30 (2003), pp. 173–193.) and Tahata et al. (K. Tahata, T. Iwashita, and S. Tomizawa, Measure of departure from symmetry of cumulative marginal probabilities for square contingency tables with ordered categories, SUT J. Math., 42 (2006), pp. 7–29.) considered the measures which represent the degree of departure from the marginal homogeneity (MH) model. The present paper proposes a measure that represents the degree of departure from the conditional MH, given that an observation will fall in one of the off-diagonal cells of the table. The measure proposed is expressed by using the Cressie–Read power-divergence or the Patil–Taillie diversity index, which is applied for the conditional cumulative marginal probabilities given that an observation will fall in one of the off-diagonal cells of the table. When the MH model does not hold, the measure is useful for seeing how far the conditional cumulative marginal probabilities are from those with an MH structure and for comparing the degree of departure from MH in several tables. Examples are given.     

Semiparametric Estimation in Copulas with the Same Marginals

We consider semiparametric multivariate data models based on copula representation of the common distribution function. A copula is characterized by a parameter of association and marginal distribution functions. This parameter and the marginal distributions are unknown. In this article, we study the estimator of the parameter of association in copulas with the marginal distribution functions assumed as nuisance parameters restricted by the assumption that the components are identically distributed. Results of this work could be used to construct special kinds of tests of homogeneity for random vectors having dependent components.     

Marginal homogeneity,symmetry, and independence

A contingency table of the mc form provides a convenient summary of data when c individuals in a matched set9 each belonging to a different one of c classifications, are identified as belonging to one of m categories, A study in which matched sets (c=3) of 1 case, 1 hospital control, and 1 neighborhood control are classified into one of m=4 occupational categories would be an example, Independence in the cxm tables for each of the matched sets implies symmetry in the summary mc table with consequent marginal homogeneity. Adaptation of the Mantel-Haenszel procedure for testing independence to the case of many cxm tables so as to yield a chi square with (cl)(ml) degrees of freedom (DF) provides a test of marginal homogeneity in the summary mc table. This can be viewed as a test of symmetry directed against alternatives which would make for marginal inhomogeneity and can differ     

Diagonal,weighted marginal homogeneity model and decompositions for linear diagonals-parameter symmetry model

For square contingency tables rith ordered categories, this paper proposes two kinds of extensions of marginal homogeneity model and gives decompositions for the Liseer diagonals-parameter symmetry model considered by Agresti (1983a) using the proposed models- The proposed models are also applied to an unaided vision data.     

Inference on measurements of agreement using marginal association

A statistical test concerning the comparison of two agreements for dependent observations is studied. The concept of stochastic ordering plays an important role in defining order of agreements. A one-sided likelihood ratio test for equality of two agreements is proposed. This test is closely related to the test of marginal homogeneity against marginal stochastic ordering. A real example is analyzed for illustration purposes.     

Marginal asymmetry model for square contingency tables with ordered categories

For the analysis of square contingency tables with ordered categories, this paper proposes a model which indicates the structure of marginal asymmetry. The model states that the absolute values of logarithm of ratio of the cumulative probability that an observation will fall in row category i or below and column category i+1 or above to the corresponding cumulative probability that the observation falls in column category i or below and row category i+1 or above are constant for every i. We deal with the estimation problem for the model parameter and goodness-of-fit tests. Also we discuss the relationships between the model and a measure which represents the degree of departure from marginal homogeneity. Examples are given.     

Average Collapsibility of Distribution Dependence and Quantile Regression Coefficients

Abstract. The Yule–Simpson paradox notes that an association between random variables can be reversed when averaged over a background variable. Cox and Wermuth introduced the concept of distribution dependence between two random variables X and Y, and gave two dependence conditions, each of which guarantees that reversal of qualitatively similar conditional dependences cannot occur after marginalizing over the background variable. Ma, Xie and Geng studied the uniform collapsibility of distribution dependence over a background variable W, under stronger homogeneity condition. Collapsibility ensures that associations are the same for conditional and marginal models. In this article, we use the notion of average collapsibility, which requires only the conditional effects average over the background variable to the corresponding marginal effect and investigate its conditions for distribution dependence and for quantile regression coefficients.     

DECOMPOSITIONS FOR CONDITIONAL SYMMETRY MODEL INTO PALINDROMIC SYMMETRY AND MODIFIED MARGINAL HOMOGENEITY MODELS

For square contingency tables with ordered categories, the conditional symmetry model is decomposed into the palindromic symmetry and the modified marginal homogeneity models, and moreover into the generalized palindromic symmetry model and two other models. The data on unaided vision first analysed by Stuart (1953, 1955) is analysed again by using the decompositions.     

A multivariate logit model with marginal canonical association

In this work, a generalization of the Goodman Association Model to the case of q, q > 2, categorical variables which is based on the idea of marginal modelling discussed by Gloneck–McCullagh is introduced; the difference between the proposed generalization and two models, previously introduced by Becker and Colombi, is discussed. The Becker generalization is not a marginal model because it does not imply Logit Models for the marginal probabilities, and because it is based on the conditional approach of modelling the association. The Colombi model is only partially a marginal model because it uses simple logit models for the univariate marginal probabilities but is based on the conditional approach of modelling the association. It is also shown that the maximum likelihood estimation of the parameters of the new model is feasible and, to compute the maximum likelihood estimates, an algorithm is proposed, which is a numerically convenient compromise between the constrained optimization approach of Lang and the straightforward use of the Fisher Scoring Algorithm suggested by Glonek–McCullagh.Finally, the proposed model is used to analyze a data set concerning work accidents which occurred to workers at some Italian firms during the years 1994–1996.     

Measure of departure from marginal homogeneity using marginal odds for multi-way tables with ordered categories

For square contingency tables with ordered categories, this paper proposes a measure to represent the degree of departure from the marginal homogeneity model. It is expressed as the weighted sum of the power-divergence or Patil–Taillie diversity index, and is a function of marginal log odds ratios. The measure represents the degree of departure from the equality of the log odds that the row variable is i or below instead of i+1 or above and the log odds that the column variable is i or below instead of i+1 or above for every i. The measure is also extended to multi-way tables. Examples are given.     

Extremal analysis of short series with outliers: sea-levels and athletics records

The analysis of extreme values is often required from short series which are biasedly sampled or contain outliers. Data for sea-levels at two UK east coast sites and data on athletics records for women's 3000 m track races are shown to exhibit such characteristics. Univariate extreme value methods provide a poor quantification of the extreme values for these data. By using bivariate extreme value methods we analyse jointly these data with related observations, from neighbouring coastal sites and 1500 m races respectively. We show that using bivariate methods provides substantial benefits, both in these applications and more generally with the amount of information gained being determined by the degree of dependence, the lengths and the amount of overlap of the two series, the homogeneity of the marginal characteristics of the variables and the presence and type of the outlier.     

Homogeneity Tests for Related Samples Under Censoring

We propose nonparametric homogeneity tests for related samples against much wider than location (or scale) class of alternatives including possible crossings of marginal cumulative distribution functions. The tests can be used in the case of complete and censored samples. Asymptotic distribution of the test statistics is investigated.     

Estimating odds ratios through the connected comparative experiments

In Japan rarely repeated are the comparative clinical trials with the same pair of the test and control drugs. The simple approach fur a complete iaudomized block design regarding the trials as blocks cannot therefore be applied It; strengthening the evidence uf the difference between the two drugs. In tins paper a method is discussed lo KTOVCI minimal lull hum the ruliliei ted trials in which those two drugs are respectively compared with the common third drug. The method consists of testing homogeneity of trials, forming a combined est illicit oi uf the n odds latius if the homogeneity is yeiified aiid giving the asymptotic variance of the combined estimator.In particular an approach of the multiple comparisons is taken so as to give a homogeneous subset of trials when the overall homogeneity is not satisfied. Although the paper is motivated from the comparative clinical trials, the resulting method can be applied to general incomplete block experiments if the outcomes are binoinial variables and the nil-interaction hetn-ern thc trtatnlent and block is suspicious. On the other hand in the appplications to clinical trials the other. non mathenlatical conditions for a meta-analysis such as the coincidence of tllc protocol should be satisfied as discussed by Hedges and Olkin(1983).     

Marginal distribution of Markov-switching VAR processes

We make available simple and accurate closed-form approximations to the marginal distribution of Markov-switching vector auto-regressive (MS VAR) processes. The approximation is built upon the property of MS VAR processes of being Gaussian conditionally on any semi-infinite sequence of the latent state. Truncating the semi-infinite sequence and averaging over all possible sequences of that finite length yields a mixture of normals that converges to the unknown marginal distribution as the sequence length increases. Numerical experiments confirm the viability of the approach which extends to the closely related class of MS state space models. Several applications are discussed.     

Editor's Report

There are two common methods for statistical inference on 2 × 2 contingency tables. One is the widely taught Pearson chi-square test, which uses the well-known χ²statistic. The chi-square test is appropriate for large sample inference, and it is equivalent to the Z-test that uses the difference between the two sample proportions for the 2 × 2 case. Another method is Fisher’s exact test, which evaluates the likelihood of each table with the same marginal totals. This article mathematically justifies that these two methods for determining extreme do not completely agree with each other. Our analysis obtains one-sided and two-sided conditions under which a disagreement in determining extreme between the two tests could occur. We also address the question whether or not their discrepancy in determining extreme would make them draw different conclusions when testing homogeneity or independence. Our examination of the two tests casts light on which test should be trusted when the two tests draw different conclusions.     

Log-linear models for correlated marginal totals of a contingency table

The marginal totals of a contingency table can be rearranged to form a new table. If at least twoof these totals include the same cell of the original table, the new table cannot be treated as anordinary contingency table. An iterative method is proposed to calculate maximum likelihood estimators for the expected cell frequencies of the original table under the assumption that some marginal totals (or more generally, some linear functions) of these expected frequencies satisfy a log-linear model.In some cases, a table of correlated marginal totals is treated as if it was an ordinary contingency table. The effects of ignoring the special structure of the marginal table on thedistributionof the goodness-of-fit test statistics are discussed and illustrated, with special reference to stationary Markov chains.