An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

Model Comparisons Using Information Measures

Methodologists have criticized the use of significance tests in the behavioral sciences but have failed to provide alternative data analysis strategies that appeal to applied researchers. For purposes of comparing alternate models for data, information-theoretic measures such as Akaike AIC have advantages in comparison with significance tests. Model-selection procedures based on a min(AIC) strategy, for example, are holistic rather than dependent upon a series of sometimes contradictory binary (accept/reject) decisions

Global permutation tests for multivariate ordinal data: alternatives, test statistics, and the null dilemma

We discuss two-sample global permutation tests for sets of multivariate ordinal data in possibly high-dimensional setups, motivated by the analysis of data collected by means of the World Health Organisation's International Classification of Functioning, Disability and Health. The tests do not require any modelling of the multivariate dependence structure. Specifically, we consider testing for marginal inhomogeneity and direction-independent marginal order. Max-T test statistics are known to lead to good power against alternatives with few strong individual effects. We propose test statistics that can be seen as their counterparts for alternatives with many weak individual effects. Permutation tests are valid only if the two multivariate distributions are identical under the null hypothesis. By means of simulations, we examine the practical impact of violations of this exchangeability condition. Our simulations suggest that theoretically invalid permutation tests can still be 'practically valid'. In particular, they suggest that the degree of the permutation procedure's failure may be considered as a function of the difference in group-specific covariance matrices, the proportion between group sizes, the number of variables in the set, the test statistic used, and the number of levels per variable

On optimal designs for clinical trials: An updated review

Optimization of clinical trial designs can help investigators achieve higher qualityresults for the given resource constraints. The present paper gives an overviewof optimal designs for various important problems that arise in different stages ofclinical drug development, including phase I dose–toxicity studies; phase I/II studiesthat consider early efficacy and toxicity outcomes simultaneously; phase IIdose–response studies driven by multiple comparisons (MCP), modeling techniques(Mod), or their combination (MCP–Mod); phase III randomized controlled multiarmmulti-objective clinical trials to test difference among several treatment groups;and population pharmacokinetics–pharmacodynamics experiments. We find thatmodern literature is very rich with optimal design methodologies that can be utilizedby clinical researchers to improve efficiency of drug development

A goodness of fit statistic for the geometric distribution

We propose a goodness of fit statistic for the geometric distribution and compare it in terms of power, via simulation, with the chi-square statistic. The statistic is based on the Lau-Rao theorem and can be seen as a discrete analogue of the total time on test statistic. The results suggest that the test based on the new statistic is generally superior to the chi-square test

Simultaneous Confidence Intervals for Risk Ratios in the Many-to-One Comparisons of Proportions

For many-to-one comparisons of independent binomial proportions using their ratios, we propose the MOVER approach generalizing Fieller\u27s theorem to a ratio of proportions by obtaining variance estimates in the neighbourhood of confidence limits for each proportion. We review two existing methods of inverting Wald and score test statistics and compare their performance with the proposed MOVER approach with score limits and Jeffreys limits for single proportions. As an appropriate multiplicity adjustment incorporating correlations between risk ratios, a Dunnett critical value is computed assuming a common, constant correlation of 0.5 instead of plugging in sample correlation coefficients. The simulation results suggest that the MOVER approach has desirable operating characteristics comparable to those of the method of inverting score test statistics. The MOVER with Jeffreys limits yields the median joint coverage percentage closest to the nominal level but its intervals may be wider than the other intervals in some parameter settings

Techniques for handling clustered binary data

Bibliography : leaves 143-153.Over the past few decades there has been increasing interest in clustered studies and hence much research has gone into the analysis of data arising from these studies. It is erroneous to treat clustered data, where observations within a cluster are correlated with each other, as one would treat independent data. It has been found that point estimates are not as greatly affected by clustering as are the standard deviations of the estimates. But as a consequence, confidence intervals and hypothesis testing are severely affected. Therefore one has to approach the analysis of clustered data with caution. Methods that specifically deal with correlated data have been developed. Analysis may be further complicated when the outcome variable of interest is binary rather than continuous. Methods for estimation of proportions, their variances, calculation of confidence intervals and a variety of techniques for testing the homogeneity of proportions have been developed over the years (Donner and Klar, 1993; Donner, 1989, and Rao and Scott, 1992). The methods developed within the context of experimental design generally involve incorporating the effect of clustering in the analysis. This cluster effect is quantified by the intracluster correlation and needs to be taken into account when estimating proportions, comparing proportions and in sample size calculations. In the context of observational studies, the effect of clustering is expressed by the design effect which is the inflation in the variance of an estimate that is due to selecting a cluster sample rather than an independent sample. Another important aspect of the analysis of complex sample data that is often neglected is sampling weights. One needs to recognise that each individual may not have the same probability of being selected. These weights adjust for this fact (Little et al, 1997). Methods for modelling correlated binary data have also been discussed quite extensively. Among the many models which have been proposed for analyzing binary clustered data are two approaches which have been studied and compared: the population-averaged and cluster-specific approach. The population-averaged model focuses on estimating the effect of a set of covariates on the marginal expectation of the response. One example of the population-averaged approach for parameter estimation is known as generalized estimating equations, proposed by Liang and Zeger (1986). It involves assuming that elements within a cluster are independent and then imposing a correlation structure on the set of responses. This is a useful application in longitudinal studies where a subject is regarded as a cluster. Then the parameters describe how the population-averaged response rather than a specific subject's response depends on the covariates of interest. On the other hand, cluster specific models introduce cluster to cluster variability in the model by including random effects terms, which are specific to the cluster, as linear predictors in the regression model (Neuhaus et al, 1991). Unlike the special case of correlated Gaussian responses, the parameters for the cluster specific model obtained for binary data describe different effects on the responses compared to that obtained from the population-averaged model. For longitudinal data, the parameters of a cluster-specific model describe how a specific individuals probability of a response depends on the covariates. The decision to use either of these modelling methods depends on the questions of interest. Cluster-specific models are useful for studying the effects of cluster-varying covariates and when an individual's response rather than an average population's response is the focus. The population-averaged model is useful when interest lies in how the average response across clusters changes with covariates. A criticism of this approach is that there may be no individual with the characteristics of the population-averaged model