Testing equality of two normal covariance matrices with monotone missing data

Abstract

The problem of testing equality of two multivariate normal covariance matrices is considered. Assuming that the incomplete data are of monotone pattern, a quantity similar to the Likelihood Ratio Test Statistic is proposed. A satisfactory approximation to the distribution of the quantity is derived. Hypothesis testing based on the approximate distribution is outlined. The merits of the test are investigated using Monte Carlo simulation. Monte Carlo studies indicate that the test is very satisfactory even for moderately small samples. The proposed methods are illustrated using an example.     

Heteroscedastic Global Tests that the Regression Parameters for Two or More Independent Groups are Identical

Simulation results are reported on methods that allow both within group and between group heteroscedasticity when testing the hypothesis that independent groups have identical regression parameters. The methods are based on a combination of extant techniques, but their finite-sample properties have not been studied. Included are results on the impact of removing all leverage points or just bad leverage points. The method used to identify leverage points can be important and can improve control over the Type I error probability. Results are illustrated using data from the Well Elderly II study.     

Computing maximum likelihood estimates from type II doubly censored exponential data

It is well-known that, under Type II double censoring, the maximum likelihood (ML) estimators of the location and scale parameters, θ and δ, of a twoparameter exponential distribution are linear functions of the order statistics. In contrast, when θ is known, theML estimator of δ does not admit a closed form expression. It is shown, however, that theML estimator of the scale parameter exists and is unique. Moreover, it has good large-sample properties. In addition, sharp lower and upper bounds for this estimator are provided, which can serve as starting points for iterative interpolation methods such as regula falsi. Explicit expressions for the expected Fisher information and Cramér-Rao lower bound are also derived. In the Bayesian context, assuming an inverted gamma prior on δ, the uniqueness, boundedness and asymptotics of the highest posterior density estimator of δ can be deduced in a similar way. Finally, an illustrative example is included.     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Interpreting DNA Mixtures with Related Contributors in Subdivided Populations

Abstract.  In this paper, we study the statistical interpretation of forensic DNA mixtures with related contributors in subdivided populations. Compact general formulae for match probabilities are obtained for two situations: a relative of one tested person is an unknown contributor of a DNA mixture; and two related unknowns are contributors. The effect of kinship and population structure is illustrated using a real case example.     

Estimator Choice and Fisher's Paradox: A Monte Carlo Study

This paper argues that Fisher's paradox can be explained away in terms of estimator choice. We analyse by means of Monte Carlo experiments the small sample properties of a large set of estimators (including virtually all available single-equation estimators), and compute the critical values based on the empirical distributions of the t-statistics, for a variety of Data Generation Processes (DGPs), allowing for structural breaks, ARCH effects etc. We show that precisely the estimators most commonly used in the literature, namely OLS, Dynamic OLS (DOLS) and non-prewhitened FMLS, have the worst performance in small samples, and produce rejections of the Fisher hypothesis. If one employs the estimators with the most desirable properties (i.e., the smallest downward bias and the minimum shift in the distribution of the associated t-statistics), or if one uses the empirical critical values, the evidence based on US data is strongly supportive of the Fisher relation, consistently with many theoretical models.     

Choice of the primary analysis in longitudinal clinical trials

Missing data, and the bias they can cause, are an almost ever‐present concern in clinical trials. The last observation carried forward (LOCF) approach has been frequently utilized to handle missing data in clinical trials, and is often specified in conjunction with analysis of variance (LOCF ANOVA) for the primary analysis. Considerable advances in statistical methodology, and in our ability to implement these methods, have been made in recent years. Likelihood‐based, mixed‐effects model approaches implemented under the missing at random (MAR) framework are now easy to implement, and are commonly used to analyse clinical trial data. Furthermore, such approaches are more robust to the biases from missing data, and provide better control of Type I and Type II errors than LOCF ANOVA. Empirical research and analytic proof have demonstrated that the behaviour of LOCF is uncertain, and in many situations it has not been conservative. Using LOCF as a composite measure of safety, tolerability and efficacy can lead to erroneous conclusions regarding the effectiveness of a drug. This approach also violates the fundamental basis of statistics as it involves testing an outcome that is not a physical parameter of the population, but rather a quantity that can be influenced by investigator behaviour, trial design, etc. Practice should shift away from using LOCF ANOVA as the primary analysis and focus on likelihood‐based, mixed‐effects model approaches developed under the MAR framework, with missing not at random methods used to assess robustness of the primary analysis. Copyright © 2004 John Wiley & Sons, Ltd.     

Creating a reference to a complex emergency situation using time series methods: war in Guinea-Bissau 1998-1999

Impacts of complex emergencies or relief interventions have often been evaluated by absolute mortality compared to international standardized mortality rates. A better evaluation would be to compare with local baseline mortality of the affected populations. A projection of population-based survival data into time of emergency or intervention based on information from before the emergency may create a local baseline reference. We find a log-transformed Gaussian time series model where standard errors of the estimated rates are included in the variance to have the best forecasting capacity. However, if time-at-risk during the forecasted period is known then forecasting might be done using a Poisson time series model with overdispersion. Whatever, the standard error of the estimated rates must be included in the variance of the model either in an additive form in a Gaussian model or in a multiplicative form by overdispersion in a Poisson model. Data on which the forecasting is based must be modelled carefully concerning not only calendar-time trends but also periods with excessive frequency of events (epidemics) and seasonal variations to eliminate residual autocorrelation and to make a proper reference for comparison, reflecting changes over time during the emergency. Hence, when modelled properly it is possible to predict a reference to an emergency-affected population based on local conditions. We predicted childhood mortality during the war in Guinea-Bissau 1998-1999. We found an increased mortality in the first half-year of the war and a mortality corresponding to the expected one in the last half-year of the war.     

Divergence-based estimation and testing with misclassified data

The well-known chi-squared goodness-of-fit test for a multinomial distribution is generally biased when the observations are subject to misclassification. In Pardo and Zografos (2000) the problem was considered using a double sampling scheme and ø-divergence test statistics. A new problem appears if the null hypothesis is not simple because it is necessary to give estimators for the unknown parameters. In this paper the minimum ø-divergence estimators are considered and some of their properties are established. The proposed ø-divergence test statistics are obtained by calculating ø-divergences between probability density functions and by replacing parameters by their minimum ø-divergence estimators in the derived expressions. Asymptotic distributions of the new test statistics are also obtained. The testing procedure is illustrated with an example.     

Generalized additive models for location, scale and shape

Summary.  A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y , as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.