The Asymptotic Power Of Jonckheere-Type Tests For Ordered Alternatives

For the c -sample location problem with ordered alternatives, the test proposed by Barlow et al . (1972 p. 184) is an appropriate one under the model of normality. For non-normal data, however, there are rank tests which have higher power than the test of Barlow et al ., e.g. the Jonckheere test or so-called Jonckheere-type tests recently introduced and studied by Büning & Kössler (1996). In this paper the asymptotic power of the Jonckheere-type tests is computed by using results of Hájek (1968) which may be considered as extensions of the theorem of Chernoff & Savage (1958). Power studies via Monte Carlo simulation show that the asymptotic power values provide a good approximation to the finite ones even for moderate sample sizes.     

Adaptive Jonckheere-type tests for ordered alternatives

Testing against ordered alternatives in the c -sample location problem plays an important role in statistical practice. The parametric test proposed by Barlow et al .-in the following, called the 'B-test'-is an appropriate test under the model of normality. For non-normal data, however, there are rank tests which have higher power than the B-test, such as the Jonckheere test or so-called Jonckheere-type tests introduced and studied by Buning and Kossler. However, we usually have no information about the underlying distribution. Thus, an adaptive test should be applied which takes into account the given data set. Two versions of such an adaptive test are proposed, which are based on the concept introduced by Hogg in 1974. These adaptive tests are compared with each of the single Jonckheere-type tests in the adaptive scheme and also with the B-test. It is shown via Monte Carlo simulation that the adaptive tests behave well over a broad class of symmetric distributions with short, medium and long tails, as well as for asymmetric distributions.     

The effects of covariate adjustment in generalized linear models

Results from classical linear regression regarding the effects of covariate adjustment, with respect to the issues of confounding, the precision with which an exposure effect can be estimated, and the efficiency of hypothesis tests for no treatment effect in randomized experiments, are often assumed to apply more generally to other types of regression models. In this paper results pertaining to several generalized linear models involving a dichotomous response variable are given, demonstrating that with respect to the issues of confounding and precision, for models having a linear or log link function the results of classical linear regression do generally apply, whereas for other models, including those having a logit, probit, log-log, complementary log-log, or generalized logistic link function, the results of classical linear regression do not always apply. It is also shown, however, that for any link function, covariate adjustment results in improved efficiency of hypothesis tests for no treatment effect in randomized experiments, and hence that the classical linear regression results regarding efficiency do apply for all models having a dichotomous response variable.     

Weighted Mean Survival Test Statistics: a Class of Distance Tests for Censored Survival Data

A class of test statistics is introduced which is sensitive against the alternative of stochastic ordering in the two-sample censored data problem. The test statistics for evaluating a cumulative weighted difference in survival distributions are developed while taking into account the imbalances in base-line covariates between two groups. This procedure can be used to test the null hypothesis of no treatment effect, especially when base-line hazards cross and prognostic covariates need to be adjusted. The statistics are semiparametric, not rank based, and can be written as integrated weighted differences in estimated survival functions, where these survival estimates are adjusted for covariate imbalances. The asymptotic distribution theory of the tests is developed, yielding test procedures that are shown to be consistent under a fixed alternative. The choice of weight function is discussed and relies on stability and interpretability considerations. An example taken from a clinical trial for acquired immune deficiency syndrome is presented.     

Rank correlation methods for missing data

The subject of rank correlation has had a rich history. It has been used in numerous applications in tests for trend and for independence. However, little has been said about how to define rank correlation when the data are incomplete. The practice has often been to ignore missing observations and to define rank correlation for the smaller complete record. We propose a new class of measures of rank correlation which are based on a notion of distance between incomplete rankings. There is the potential for a significant increase in efficiency over the approach which ignores missing observations as demonstrated by a specific case.     

Exact tests based on the Baumgartner-Weiß-Schindler statistic—A survey

It is the purpose of this paper to review recently-proposed exact tests based on the Baumgartner-Weiß-Schindler statistic and its modification. Except for the generalized Behrens-Fisher problem, these tests are broadly applicable, and they can be used to compare two groups irrespective of whether or not ties occur. In addition, a nonparametric trend test and a trend test for binomial proportions are possible. These exact tests are preferable to commonly-applied tests, such as the Wilcoxon rank sum test, in terms of both type I error rate and power.     

A lack-of-fit test for parametric zero-inflated Poisson models

Count data often contain many zeros. In parametric regression analysis of zero-inflated count data, the effect of a covariate of interest is typically modelled via a linear predictor. This approach imposes a restrictive, and potentially questionable, functional form on the relation between the independent and dependent variables. To address the noted restrictions, a flexible parametric procedure is employed to model the covariate effect as a linear combination of fixed-knot cubic basis splines or B-splines. The semiparametric zero-inflated Poisson regression model is fitted by maximizing the likelihood function through an expectation–maximization algorithm. The smooth estimate of the functional form of the covariate effect can enhance modelling flexibility. Within this modelling framework, a log-likelihood ratio test is used to assess the adequacy of the covariate function. Simulation results show that the proposed test has excellent power in detecting the lack of fit of a linear predictor. A real-life data set is used to illustrate the practicality of the methodology.     

Linear rank tests under general alternatives,with application to summary statistics computed from repeated measures data

Linear rank tests are used extensively for comparing two or more groups of continuous outcomes. Tests in this class retain proper test size with minimal assumptions and can have high efficiency towards an alternative of interest. In recent years, these tests have been increasingly used in settings where an individual's observation is itself a scalar summary of several outcome measures. Here, simple distributional structures on the outcome variables can lead to complex differences between the distributions of summary statistics of the comparison groups. The local asymptotic power of linear rank tests when the groups are assumed to differ by a location or scale alternative has been studied in detail. However, not much is known about their behavior for other types of alternatives. To address this, we derive the asymptotic distribution of linear rank tests under a general contiguous alternative and then investigate the implications for location–scale families and more general settings, including an example drawn from an AIDS clinical trial where the continuous outcome is a summary statistic computed from repeated measures of a biological marker.     

Risk Prediction for Prostate Cancer Recurrence Through Regularized Estimation with Simultaneous Adjustment for Nonlinear Clinical Effects

In biomedical studies, it is of substantial interest to develop risk prediction scores using high-dimensional data such as gene expression data for clinical endpoints that are subject to censoring. In the presence of well-established clinical risk factors, investigators often prefer a procedure that also adjusts for these clinical variables. While accelerated failure time (AFT) models are a useful tool for the analysis of censored outcome data, it assumes that covariate effects on the logarithm of time-to-event are linear, which is often unrealistic in practice. We propose to build risk prediction scores through regularized rank estimation in partly linear AFT models, where high-dimensional data such as gene expression data are modeled linearly and important clinical variables are modeled nonlinearly using penalized regression splines. We show through simulation studies that our model has better operating characteristics compared to several existing models. In particular, we show that there is a non-negligible effect on prediction as well as feature selection when nonlinear clinical effects are misspecified as linear. This work is motivated by a recent prostate cancer study, where investigators collected gene expression data along with established prognostic clinical variables and the primary endpoint is time to prostate cancer recurrence. We analyzed the prostate cancer data and evaluated prediction performance of several models based on the extended c statistic for censored data, showing that 1) the relationship between the clinical variable, prostate specific antigen, and the prostate cancer recurrence is likely nonlinear, i.e., the time to recurrence decreases as PSA increases and it starts to level off when PSA becomes greater than 11; 2) correct specification of this nonlinear effect improves performance in prediction and feature selection; and 3) addition of gene expression data does not seem to further improve the performance of the resultant risk prediction scores.     

Informative Retesting

In situations where individuals are screened for an infectious disease or other binary characteristic and where resources for testing are limited, group testing can offer substantial benefits. Group testing, where subjects are tested in groups (pools) initially, has been successfully applied to problems in blood bank screening, public health, drug discovery, genetics, and many other areas. In these applications, often the goal is to identify each individual as positive or negative using initial group tests and subsequent retests of individuals within positive groups. Many group testing identification procedures have been proposed; however, the vast majority of them fail to incorporate heterogeneity among the individuals being screened. In this paper, we present a new approach to identify positive individuals when covariate information is available on each. This covariate information is used to structure how retesting is implemented within positive groups; therefore, we call this new approach "informative retesting." We derive closed-form expressions and implementation algorithms for the probability mass functions for the number of tests needed to decode positive groups. These informative retesting procedures are illustrated through a number of examples and are applied to chlamydia and gonorrhea testing in Nebraska for the Infertility Prevention Project. Overall, our work shows compelling evidence that informative retesting can dramatically decrease the number of tests while providing accuracy similar to established non-informative retesting procedures.     

Rank tests for the k-sample problem with restricted alternatives

An asymptotically maximin most powerful rank test among somewhere asymptotically most powerful linear rank tests with scores generating function cf> is derived for each of the simple order alternative, the simple loop alternative and the simple tree alternative in the k-sample problem. The comparisons of the tests obtained with the rank analogues of the Bartholomew's xv tests are made in terms of local asymptotic relative efficiency. It is found that our tests are better than the rank analogues of the xk tests. Furthermore, the asymptotic equivalence of the ranking by the pooled sample to the ranking in pairs are discuss¬ed and the tests which are asymptotically equivalent to ours are given.     

Classical testing in functional linear models

We extend four tests common in classical regression – Wald, score, likelihood ratio and F tests – to functional linear regression, for testing the null hypothesis, that there is no association between a scalar response and a functional covariate. Using functional principal component analysis, we re-express the functional linear model as a standard linear model, where the effect of the functional covariate can be approximated by a finite linear combination of the functional principal component scores. In this setting, we consider application of the four traditional tests. The proposed testing procedures are investigated theoretically for densely observed functional covariates when the number of principal components diverges. Using the theoretical distribution of the tests under the alternative hypothesis, we develop a procedure for sample size calculation in the context of functional linear regression. The four tests are further compared numerically for both densely and sparsely observed noisy functional data in simulation experiments and using two real data applications.     

Ecological Bias: Use of Maximum-Entropy Approximations

The focus of geographical studies in epidemiology has recently moved towards looking for effects of exposures based on data taken at local levels of aggregation (i.e. small areas). This paper investigates how regression coefficients measuring covariate effects at the point level are modified under aggregation. Changing the level of aggregation can lead to completely different conclusions about exposure–effect relationships, a phenomenon often referred to as ecological bias. With partial knowledge of the within‐area distribution of the exposure variable, the notion of maximum entropy can be used to approximate that part of the distribution that is unknown. From the approximation, an expression for the ecological bias is obtained; simulations and an example show that the maximum‐entropy approximation is often better than other commonly used approximations.     

Weighted-bootstrap alignment of explanatory variables

Adjustment for covariates is a time-honored tool in statistical analysis and is often implemented by including the covariates that one intends to adjust as additional predictors in a model. This adjustment often does not work well when the underlying model is misspecified. We consider here the situation where we compare a response between two groups. This response may depend on a covariate for which the distribution differs between the two groups one intends to compare. This creates the potential that observed differences are due to differences in covariate levels rather than “genuine” population differences that cannot be explained by covariate differences. We propose a bootstrap-based adjustment method. Bootstrap weights are constructed with the aim of aligning bootstrap–weighted empirical distributions of the covariate between the two groups. Generally, the proposed weighted-bootstrap algorithm can be used to align or match the values of an explanatory variable as closely as desired to those of a given target distribution. We illustrate the proposed bootstrap adjustment method in simulations and in the analysis of data on the fecundity of historical cohorts of French-Canadian women.     

New tests for stochastic order with application to case control studies

It is shown that if a binary regression function is increasing then retrospective sampling induces a stochastic ordering of the covariate distributions among the responders, which we call cases, and the non-responders, which we call controls. We also show that if the covariate distributions are stochastically ordered then the regression function must be increasing. This means that testing whether the regression function is monotone is equivalent to testing whether the covariate distributions are stochastically ordered. Capitalizing on these new probabilistic observations we proceed to develop two new non-parametric tests for stochastic order. The new tests are based on either the maximally selected, or integrated, chi-bar statistic of order one. The tests are easy to compute and interpret and their large sampling distributions are easily found. Numerical comparisons show that they compare favorably with existing methods in both small and large samples. We emphasize that the new tests are applicable to any testing problem involving two stochastically ordered distributions.     

A generalized estimating equation approach to modelling incompatible data formats with covariate measurement error: application to human immunodeficiency virus immune markers

The integration of technological advances into research studies often raises an issue of incompatibility of data. This problem is common to longitudinal and multicentre studies, taking the form of changes in the definitions, acquisition of data or measuring instruments of some study variables. In our case of studying the relationship between a marker of immune response to human immunodeficiency virus and human immunodeficiency virus infection status, using data from the Multi-Center AIDS Cohort Study, changes in the manufactured tests used for both variables occurred throughout the study, resulting in data with different manufactured scales. In addition, the latent nature of the immune response of interest necessitated a further consideration of a measurement error component. We address the general issue of incompatibility of data, together with the issue of covariate measurement error, in a unified, generalized linear model setting with inferences based on the generalized estimating equation framework. General conditions are constructed to ensure consistent estimates and their variances for the primary model of interest, with the asymptotic behaviour of resulting estimates examined under a variety of modelling scenarios. The approach is illustrated by modelling a repeated ordinal response with incompatible formats, as a function of a covariate with incompatible formats and measurement error, based on the Multi-Center AIDS Cohort Study data.     

Nonparametric tests for scale shift at an unknown time point

A class of linear rank tests is suggested for testing a shift in scale at an unknown time point in a sequence of independent observations. The tests,based on inverse normal scores and on ordered exponential scores,are shown to be asymptotically as efficient as their distribution-oriented competitors. Critical values and powers for these two rank tests are also discussed.     

Overcoming biases and misconceptions in ecological studies

The aggregate data study design provides an alternative group level analysis to ecological studies in the estimation of individual level health risks. An aggregate model is derived by aggregating a plausible individual level relative rate model within groups, such that population-based disease rates are modelled as functions of individual level covariate data. We apply an aggregate data method to a series of fictitious examples from a review paper by Greenland and Robins which illustrated the problems that can arise when using the results of ecological studies to make inference about individual health risks. We use simulated data based on their examples to demonstrate that the aggregate data approach can address many of the sources of bias that are inherent in typical ecological analyses, even though the limited between-region covariate variation in these examples reduces the efficiency of the aggregate study. The aggregate method has the potential to estimate exposure effects of interest in the presence of non-linearity, confounding at individual and group levels, effect modification, classical measurement error in the exposure and non-differential misclassification in the confounder.     

Ordered Regressions

There are often situations where two or more regression functions are ordered over a range of covariate values. In this paper, we develop efficient constrained estimation and testing procedures for such models. Specifically, necessary and sufficient conditions for ordering generalized linear regressions are given and shown to unify previous results obtained for simple linear regression, for polynomial regression and in the analysis of covariance models. We show that estimating the parameters of ordered linear regressions requires either quadratic programming or semi‐infinite programming, depending on the shape of the covariate space. A distance‐type test for order is proposed. Simulations demonstrate that the proposed methodology improves the mean square error and power compared with the usual, unconstrained, estimation and testing procedures. Improvements are often substantial. The methodology is extended to order generalized linear models where convex semi‐infinite programming plays a role. The methodology is motivated by, and applied to, a hearing loss study.     

Data Driven Rank Test for Two-Sample Problem

Traditional linear rank tests are known to possess low power for large spectrum of alternatives. In this paper we introduce a new rank test possessing a considerably larger range of sensitivity than linear rank tests. The new test statistic is a sum of squares of some linear rank statistics while the number of summands is chosen via a data-based selection rule. Simulations show that the new test possesses high and stable power in situations when linear rank tests completely break down, while simultaneously it has almost the same power under alternatives which can be detected by standard linear rank tests. Our approach is illustrated by some practical examples. Theoretical support is given by deriving asymptotic null distribution of the test statistic and proving consistency of the new test under essentially any alternative.