Exact methods for testing homogeneity of proportions for multiple groups of paired binary data

We consider four exact procedures to test the homogeneity of proportions for correlated multiple clustered data. Exact procedures are compared with the asymptotic approach based on the score statistic. We use a real example from a double-blind clinical trial studying the treatment of otitis media to illustrate the various test procedures and provide extensive numerical studies to compare procedures with regards to Type I error rates and powers under the unconditional framework. The exact unconditional procedure based on estimation followed by maximization is generally more powerful than other procedures.     

Bayesian Confidence Interval for the Difference of Two Proportions in the Matched-Paired Design

This article studies the construction of Bayesian confidence interval for the difference of two proportions in the matched-pair design, and applies it to the equiva-lence or non inferiority test. Under the Dirichlet prior distribution, the exact posterior distribution of difference of two proportions is derived. The tail confidence interval and the highest posterior density (HPD) interval are studied, and their frequentist performance are investigated by simulation in terms of the mean coverage probability of interval. Our results suggest to use tail interval at Jeffreys prior for testing equivalence or non inferiority in matched-pair design.     

The exact unconditional z-pooled test for equality of two binomial probabilities: optimal choice of the Berger and Boos confidence coefficient

Exact unconditional tests for comparing two binomial probabilities are generally more powerful than conditional tests like Fisher's exact test. Their power can be further increased by the Berger and Boos confidence interval method, where a p-value is found by restricting the common binomial probability under H ₀ to a 1?γ confidence interval. We studied the average test power for the exact unconditional z-pooled test for a wide range of cases with balanced and unbalanced sample sizes, and significance levels 0.05 and 0.01. The detailed results are available online on the web. Among the values 10^?3, 10^?4, …, 10^?10, the value γ=10^?4 gave the highest power, or close to the highest power, in all the cases we looked at, and can be given as a general recommendation as an optimal γ.     

Structural properties of UMPU-tests for 2×2 tables and some applications

The paper is concerned with structural properties of the acceptance regions of uniformly most powerful unbiased tests (UMPU-tests) for one- and two-sided hypotheses for 2×2 tables as, for instance, the comparison of two proportions or testing for association. These tests can be considered as randomized versions of Fisher's exact tests. A series of monotonicity and unimodality properties will be proved. These properties are equivalent to a symmetry and convexity condition often required for powerful unconditional tests. Knowledge of such properties allows a fast and in some sense recursive calculation of the critical values of the UMPU-tests which is important if a repeated calculation of all critical values for different sample sizes or different levels is required. This is, for example, the case if the unconditional power has to be controlled over a certain subset of the alternative, or, if one is interested in powerful unconditional non-randomized tests generated by a UMPU-test. Our results also imply some useful properties of the two-dimensional unconditional power function. On the other hand, we found some less nice properties of the UMPU-tests, too.     

Applications of schur theory to reliability inference for k of n systems

The results of Hoeffding (1956), Pledger and Proschan (1971), Gleser (1975) and Boland and Proschan (1983) are used to obtain Buehler (1957) 1-α lower confidence limits for the reliability of k of n systems of independent components when the subsystem data have equal sample sizes and the observed failures satisfy certain conditions. To the best of our knowledge, for k ≠ 1 or n, this is the first time the exact optimal lower confidence limits for system reliability have been given. The observed failure vectors are a generalization of key test results for k of n systems, k ≠ n (Soms (1984) and Winterbottom (1974)). Two examples applying the above theory are also given.     

Confidence Intervals for the Weighted Sum of Two Independent Binomial Proportions

Confidence intervals for the difference of two binomial proportions are well known, however, confidence intervals for the weighted sum of two binomial proportions are less studied. We develop and compare seven methods for constructing confidence intervals for the weighted sum of two independent binomial proportions. The interval estimates are constructed by inverting the Wald test, the score test and the Likelihood ratio test. The weights can be negative, so our results generalize those for the difference between two independent proportions. We provide a numerical study that shows that these confidence intervals based on large‐sample approximations perform very well, even when a relatively small amount of data is available. The intervals based on the inversion of the score test showed the best performance. Finally, we show that as for the difference of two binomial proportions, adding four pseudo‐outcomes to the Wald interval for the weighted sum of two binomial proportions improves its coverage significantly, and we provide a justification for this correction.     

A more powerful unconditional exact test of homogeneity for 2 × c contingency table analysis

The classical unconditional exact p-value test can be used to compare two multinomial distributions with small samples. This general hypothesis requires parameter estimation under the null which makes the test severely conservative. Similar property has been observed for Fisher's exact test with Barnard and Boschloo providing distinct adjustments that produce more powerful testing approaches. In this study, we develop a novel adjustment for the conservativeness of the unconditional multinomial exact p-value test that produces nominal type I error rate and increased power in comparison to all alternative approaches. We used a large simulation study to empirically estimate the 5th percentiles of the distributions of the p-values of the exact test over a range of scenarios and implemented a regression model to predict the values for two-sample multinomial settings. Our results show that the new test is uniformly more powerful than Fisher's, Barnard's, and Boschloo's tests with gains in power as large as several hundred percent in certain scenarios. Lastly, we provide a real-life data example where the unadjusted unconditional exact test wrongly fails to reject the null hypothesis and the corrected unconditional exact test rejects the null appropriately.     

Corrected profile likelihood confidence interval for binomial paired incomplete data

Clinical trials often use paired binomial data as their clinical endpoint. The confidence interval is frequently used to estimate the treatment performance. Tang et al. (2009) have proposed exact and approximate unconditional methods for constructing a confidence interval in the presence of incomplete paired binary data. The approach proposed by Tang et al. can be overly conservative with large expected confidence interval width (ECIW) in some situations. We propose a profile likelihood‐based method with a Jeffreys' prior correction to construct the confidence interval. This approach generates confidence interval with a much better coverage probability and shorter ECIWs. The performances of the method along with the corrections are demonstrated through extensive simulation. Finally, three real world data sets are analyzed by all the methods. Statistical Analysis System (SAS) codes to execute the profile likelihood‐based methods are also presented. Copyright © 2013 John Wiley & Sons, Ltd.     

Bootstrap adjustments for empirical bayes interval estimates of small-area proportions

Empirical Bayes approaches have often been applied to the problem of estimating small-area parameters. As a compromise between synthetic and direct survey estimators, an estimator based on an empirical Bayes procedure is not subject to the large bias that is sometimes associated with a synthetic estimator, nor is it as variable as a direct survey estimator. Although the point estimates perform very well, naïve empirical Bayes confidence intervals tend to be too short to attain the desired coverage probability, since they fail to incorporate the uncertainty which results from having to estimate the prior distribution. Several alternative methodologies for interval estimation which correct for the deficiencies associated with the naïve approach have been suggested. Laird and Louis (1987) proposed three types of bootstrap for correcting naïve empirical Bayes confidence intervals. Calling the methodology of Laird and Louis (1987) an unconditional bias-corrected naïve approach, Carlin and Gelfand (1991) suggested a modification to the Type III parametric bootstrap which corrects for bias in the naïve intervals by conditioning on the data. Here we empirically evaluate the Type II and Type III bootstrap proposed by Laird and Louis, as well as the modification suggested by Carlin and Gelfand (1991), with the objective of examining coverage properties of empirical Bayes confidence intervals for small-area proportions.     

A Nonrandomized,Nonconservative Version of the Fisher Exact Test

The Fisher exact test has been unjustly dismissed by some as ‘only conditional,’ whereas it is unconditionally the uniform most powerful test among all unbiased tests, tests of size α and with power greater than its nominal level of significance α. The problem with this truly optimal test is that it requires randomization at the critical value(s) to be of size α. Obviously, in practice, one does not want to conclude that ‘with probability x the we have a statistical significant result.’ Usually, the hypothesis is rejected only if the test statistic's outcome is more extreme than the critical value, reducing the actual size considerably.

The randomized unconditional Fisher exact is constructed (using Neyman–structure arguments) by deriving a conditional randomized test randomizing at critical values c(t) by probabilities γ(t), that both depend on the total number of successes T (the complete-sufficient statistic for the nuisance parameter—the common success probability) conditioned upon.

In this paper, the Fisher exact is approximated by deriving nonrandomized conditional tests with critical region including the critical value only if γ (t) > γ₀, for a fixed threshold value γ₀, such that the size of the unconditional modified test is for all value of the nuisance parameter—the common success probability—smaller, but as close as possible to α. It will be seen that this greatly improves the size of the test as compared with the conservative nonrandomized Fisher exact test.

Size, power, and p value comparison with the (virtual) randomized Fisher exact test, and the conservative nonrandomized Fisher exact, Pearson's chi-square test, with the more competitive mid-p value, the McDonald's modification, and Boschloo's modifications are performed under the assumption of two binomial samples.     

Comparing two independent incidence rates using conditional and unconditional exact tests

Several unconditional exact tests, which are constructed to control the Type I error rate at the nominal level, for comparing two independent Poisson rates are proposed and compared to the conditional exact test using a binomial distribution. The unconditional exact test using binomial p-value, likelihood ratio, or efficient score as the test statistic improves the power in general, and are therefore recommended. Unconditional exact tests using Wald statistics, whether on the original or square-root scale, may be substantially less powerful than the conditional exact test, and is not recommended. An example is provided from a cardiovascular trial.     

Highly Efficient Designs to Handle the Incorrect Specification of Linear Mixed Models

The asymptotic chi-square test for testing the Hardy–Weinberg law is unreliable in either small or unbalanced samples. As an alternative, either the unconditional or conditional exact test might be used. It is known that the unconditional exact test has greater power than the conditional exact test in small samples. In this article, we show that the conditional exact test is more powerful than the unconditional exact test in large samples. This result is useful in extremely unbalanced cases with large sample sizes which are often obtained when a rare allele exists.     

Exact unconditional testing procedures for comparing two independent Poisson rates

We consider seven exact unconditional testing procedures for comparing adjusted incidence rates between two groups from a Poisson process. Exact tests are always preferable due to the guarantee of test size in small to medium sample settings. Han [Comparing two independent incidence rates using conditional and unconditional exact tests. Pharm Stat. 2008;7(3):195–201] compared the performance of partial maximization p-values based on the Wald test statistic, the likelihood ratio test statistic, the score test statistic, and the conditional p-value. These four testing procedures do not perform consistently, as the results depend on the choice of test statistics for general alternatives. We consider the approach based on estimation and partial maximization, and compare these to the ones studied by Han (2008) for testing superiority. The procedures are compared with regard to the actual type I error rate and power under various conditions. An example from a biomedical research study is provided to illustrate the testing procedures. The approach based on partial maximization using the score test is recommended due to the comparable performance and computational advantage in large sample settings. Additionally, the approach based on estimation and partial maximization performs consistently for all the three test statistics, and is also recommended for use in practice.     

Some remarks on conditional and unconditional inference for location-scale models

Conditional and unconditional confidence intervals have been compared by Grice, Bain, and Engelhardt (Commun. Statist. B7 (1978), 515–524) in terms of the location-scale model with double-exponential distribution form. Preference was found for the conditional intervals based on mean length and coverage probability for untrue parameters values. These two criteria for a location-scale system are shown to be inappropriate criteria for assessing the conditional versus unconditional approaches to inference. The usual ancillarity concept is also noted to be inappropriate. Support for many conditional analyses, however, is found in a more careful formulation of the statistical model.     

Homogeneity test, sample size determination and interval construction of difference of two proportions in stratified bilateral-sample designs

In stratified otolaryngologic (or ophthalmologic) studies, the misleading results may be obtained when ignoring the confounding effect and the correlation between responses from two ears. Score statistic and Wald-type statistic are presented to test equality in a stratified bilateral-sample design, and their corresponding sample size formulae are given. Score statistic for testing homogeneity of difference between two proportions and score confidence interval of the common difference of two proportions in a stratified bilateral-sample design are derived. Empirical results show that (1) score statistic and Wald-type statistic based on dependence model assumption outperform other statistics in terms of the type I error rates; (2) score confidence interval demonstrates reasonably good coverage property; (3) sample size formula via Wald-type statistic under dependence model assumption is rather accurate. A real example is used to illustrate the proposed methodologies.     

Extending the Barnard’s test to non-inferiority

In 1945, George Alfred Barnard presented an unconditional exact test to compare two independent proportions. Critical regions for this test, by construction accomplish the very useful property of being Barnard convex sets. Besides, there are empirical findings suggesting that Barnard’s test is the most generally powerful. For Barnard’s test, calculation of critical regions is complicated due that they are constructed in an iterative form until is obtained a test size, as close as possible to the nominal significance level and less than or equal to it. In this article we present an extension to non-inferiority of this very leading test. This extension was contructed for any dissimilarity measure and tables were constructed for the difference between proportions. Also we calculate the critical regions for this extended test for sample sizes less or equal than 30, nominal significance level 0.01, 0.025, 0.05, and 0.10 and for non-inferiority margins 0.05, 0.10, 0.15, and 0.20. Additionally, we computed test sizes for the mentioned configurations. To do this calculations, we have written a program in the R environment.     

Comparison of conditional and unconditional confidence intervals for the double exponential distribution

Conditional confidence intervals for the location parameter of the double exponential distribution based on maximum likelihood estimators conditioned on a set of ancillary statistics and the corresponding unconditional confidence intervals based on the maximum likelihood estimators alone are compared in two ways. Monte Carlo techniques are used and the conditional approach appears to give slightly better results although agreement as n becomes larger is noted     

Exact Likelihood Inference for Two Exponential Populations Under Joint Progressive Type-II Censoring

Comparative lifetime experiments are of great importance when the interest is in ascertaining the relative merits of two competing products with regard to their reliability. In this article, we consider two exponential populations and when joint progressive Type-II censoring is implemented on the two samples. We then derive the moment generating functions and the exact distributions of the maximum likelihood estimators (MLEs) of the mean lifetimes of the two exponential populations under such a joint progressive Type-II censoring. We then discuss the exact lower confidence bounds, exact confidence intervals, and simultaneous confidence regions. Next, we discuss the corresponding approximate results based on the asymptotic normality of the MLEs as well as those based on the Bayesian method. All these confidence intervals and regions are then compared by means of Monte Carlo simulations with those obtained from bootstrap methods. Finally, an illustrative example is presented in order to illustrate all the methods of inference discussed here.     

Exact likelihood ratio and score confidence intervals for the binomial proportion

Many methods are available for computing a confidence interval for the binomial parameter, and these methods differ in their operating characteristics. It has been suggested in the literature that the use of the exact likelihood ratio (LR) confidence interval for the binomial proportion should be considered. This paper provides an evaluation of the operating characteristics of the two‐sided exact LR and exact score confidence intervals for the binomial proportion and compares these results to those for three other methods that also strictly maintain nominal coverage: Clopper‐Pearson, Blaker, and Casella. In addition, the operating characteristics of the two‐sided exact LR method and exact score method are compared with those of the corresponding asymptotic methods to investigate the adequacy of the asymptotic approximation. Copyright © 2013 John Wiley & Sons, Ltd.     

On an Asymptotic Theory of Conditional and Unconditional Coverage Probabilities of Empirical Bayes Confidence Intervals

Empirical Bayes (EB) methodology is now widely used in statistics. However, construction of EB confidence intervals is still very limited. Following Cox (1975 ), Hill (1990 ) and Carlin & Gelfand (1990 , 1991 ), we consider EB confidence intervals, which are adjusted so that the actual coverage probabilities asymptotically meet the target coverage probabilities up to the second order. We consider both unconditional and conditional coverage, conditioning being done with respect to an ancillary statistic.