An exact upper limit for the variance bias in a carry-over model with correlated errors

The analysis of crossover designs assuming i.i.d. errors leads to biased variance estimates whenever the true covariance structure is not spherical. As a result, the OLS F-test for the equality of the direct effects of the treatments is not valid. Bellavance et al. [1996. Biometrics 52, 607–612] use simulations to show that a modified F-test based on an estimate of the within subjects covariance matrix allows for nearly unbiased tests. Kunert and Utzig [1993. JRSS B 55, 919–927] propose an alternative test that does not need an estimate of the covariance matrix. Instead, they correct the F-statistic by multiplying by a constant based on the worst-case scenario. However, for designs with more than three observations per subject, Kunert and Utzig (1993) only give a rough upper bound for the worst-case variance bias. This may lead to overly conservative tests. In this paper we derive an exact upper limit for the variance bias due to carry-over for an arbitrary number of observations per subject. The result holds for a certain class of highly efficient balanced crossover designs.     

Some factors affecting statistical power of approximate tests in the linear mixed model for longitudinal data

Different longitudinal study designs require different statistical analysis methods and different methods of sample size determination. Statistical power analysis is a flexible approach to sample size determination for longitudinal studies. However, different power analyses are required for different statistical tests which arises from the difference between different statistical methods. In this paper, the simulation-based power calculations of F-tests with Containment, Kenward-Roger or Satterthwaite approximation of degrees of freedom are examined for sample size determination in the context of a special case of linear mixed models (LMMs), which is frequently used in the analysis of longitudinal data. Essentially, the roles of some factors, such as variance–covariance structure of random effects [unstructured UN or factor analytic FA0], autocorrelation structure among errors over time [independent IND, first-order autoregressive AR1 or first-order moving average MA1], parameter estimation methods [maximum likelihood ML and restricted maximum likelihood REML] and iterative algorithms [ridge-stabilized Newton-Raphson and Quasi-Newton] on statistical power of approximate F-tests in the LMM are examined together, which has not been considered previously. The greatest factor affecting statistical power is found to be the variance–covariance structure of random effects in the LMM. It appears that the simulation-based analysis in this study gives an interesting insight into statistical power of approximate F-tests for fixed effects in LMMs for longitudinal data.     

Comparison of unweighted and weighted rank based tests for an ordered alternative in randomized complete block designs

In randomized complete block designs, a monotonic relationship among treatment groups may already be established from prior information, e.g., a study with different dose levels of a drug. The test statistic developed by Page and another from Jonckheere and Terpstra are two unweighted rank based tests used to detect ordered alternatives when the assumptions in the traditional two-way analysis of variance are not satisfied. We consider a new weighted rank based test by utilizing a weight for each subject based on the sample variance in computing the new test statistic. The new weighted rank based test is compared with the two commonly used unweighted tests with regard to power under various conditions. The weighted test is generally more powerful than the two unweighted tests when the number of treatment groups is small to moderate.     

Order Statistics from the Generalized Exponential Distribution and Applications

With linear dispersion effects, the standard factorial designs are not optimal estimation of a mean model. A sequential two-stage experimental design procedure has been proposed that first estimates the variance structure, and then uses the variance estimates and the variance optimality criterion to develop a second stage design that efficiency estimates the mean model. This procedure has been compared to an equal replicate design analyzed by ordinary least squares, and found to be a superior procedure in many situations.

However with small first stage sample sizes the variance estiamtes are not reliable, and hence an alternative procedure could be more beneficial. For this reason a Bayesian modification to the two-stage procedure is proposed which will combine the first stage variance estiamtes with some prior variance information that will produce a more efficient procedure. This Bayesian procedure will be compared to the non-Bayesian twostage procedure and to the two one-stage alternative procedures listed above. Finally, a recommendation will be made as to which procedure is preferred in certain situations.     

On some optimal fractional 2m factorial designs of resolution V

This paper presents the trace of the covariance matrix of the estimates of effects based on a fractional 2^m factorial (2^m-FF) design T of resolution V for the following two cases: One is the case where T is constructed by adding some restricted assemblies to an orthogonal array. The other is one where T is constructed by removing some restricted assemblies from an orthogonal array of index unity. In the class of 2^m-FF designs of resolution V considered here, optimal designs with respect to the trace criterion, i.e. A-optimal, are presented for m = 4, 5, and 6 and for a range of practical values of N (the total number of assemblies). Some of them are better than the corresponding A-optimal designs in the class of balanced fractional 2^m factorial designs of resolution V obtained by Srivastava and Chopra (1971b) in such a sense that the trace of the covariance matrix of the estimates is small.     

Multiple comparisons for an unbalanced a × b design under mixed models with interaction

Consider a two-way factorial experiment involving a “treatment” factor A with fixed effects, a “blocking” factor B with random effects, and interaction effects perhaps non-negligible. The degree of balance required for multiple comparison procedures to be applicable for the comparison of the treatment effects using ordinary least-squares estimates is investigated. For main effects to be estimated independently of MSAB, a sufficient condition is that the design consist of identical blocks, a strong condition of proportional frequencies. Surprisingly, under this condition of proportional frequencies, MSAB does not provide an appropriate variance estimate for inferences on each treatment contrast, even though the statistics F = MSA/MSAB is appropriate for testing equality of the treatment effects. In short, when factor B is random, standard methods of multiple comparisons apply using the interaction mean square MSAB as a variance estimator only when the treatment-block incidences n_n are constant. Nevertheless, for designs with identical blocks, appropriate variance estimates can be identified to allow for conservative or approximate multiple comparisons. This is illustrated for certain treatment balanced designs for comparisons with a control.     

Effect of heteroscedasticity between treatment groups on mixed‐effects models for repeated measures

Mixed‐effects models for repeated measures (MMRM) analyses using the Kenward‐Roger method for adjusting standard errors and degrees of freedom in an “unstructured” (UN) covariance structure are increasingly becoming common in primary analyses for group comparisons in longitudinal clinical trials. We evaluate the performance of an MMRM‐UN analysis using the Kenward‐Roger method when the variance of outcome between treatment groups is unequal. In addition, we provide alternative approaches for valid inferences in the MMRM analysis framework. Two simulations are conducted in cases with (1) unequal variance but equal correlation between the treatment groups and (2) unequal variance and unequal correlation between the groups. Our results in the first simulation indicate that MMRM‐UN analysis using the Kenward‐Roger method based on a common covariance matrix for the groups yields notably poor coverage probability (CP) with confidence intervals for the treatment effect when both the variance and the sample size between the groups are disparate. In addition, even when the randomization ratio is 1:1, the CP will fall seriously below the nominal confidence level if a treatment group with a large dropout proportion has a larger variance. Mixed‐effects models for repeated measures analysis with the Mancl and DeRouen covariance estimator shows relatively better performance than the traditional MMRM‐UN analysis method. In the second simulation, the traditional MMRM‐UN analysis leads to bias of the treatment effect and yields notably poor CP. Mixed‐effects models for repeated measures analysis fitting separate UN covariance structures for each group provides an unbiased estimate of the treatment effect and an acceptable CP. We do not recommend MMRM‐UN analysis using the Kenward‐Roger method based on a common covariance matrix for treatment groups, although it is frequently seen in applications, when heteroscedasticity between the groups is apparent in incomplete longitudinal data.     

Partially replicated two‐level fractional factorial designs

In a two‐level factorial experiment, the authors consider designs with partial duplication which permit estimation of the constant term, all main effects and some specified two‐factor interactions, assuming that the other effects are negligible. They construct parallel‐flats designs with two identical parallel flats that meet prior specifications; they also consider classes of 3‐flat and 4‐flat designs. They show that the designs obtained can have a very simple covariance structure and high D‐efficiency. They give an algorithm from which they generate a series of practical designs with run sizes 12, 16, 24, and 32.     

Granger Causality Test in the Presence of Spillover Effects

In this article, we investigate the effect of spillover (i.e., causality in variance) on the reliability of Granger causality test based on ordinary least square estimates. We studied eight different versions of the test both, with and without Whites heteroskedasticity consistent covariance matrix (HCCME). The properties of the tests are investigated by means of a Monte Carlo experiment where 21 different data generating processes (DGP) are used and a number of factors that might affect the test are varied. The result shows that the best choice to test for Granger causality under the presence of spillover is the Lagrange Multiplier test with HCCME.     

Design considerations for small experiments and simple logistic regression

Inference for a generalized linear model is generally performed using asymptotic approximations for the bias and the covariance matrix of the parameter estimators. For small experiments, these approximations can be poor and result in estimators with considerable bias. We investigate the properties of designs for small experiments when the response is described by a simple logistic regression model and parameter estimators are to be obtained by the maximum penalized likelihood method of Firth [Firth, D., 1993, Bias reduction of maximum likelihood estimates. Biometrika, 80, 27–38]. Although this method achieves a reduction in bias, we illustrate that the remaining bias may be substantial for small experiments, and propose minimization of the integrated mean square error, based on Firth's estimates, as a suitable criterion for design selection. This approach is used to find locally optimal designs for two support points.     

Estimating the Burr XII Parameters in Constant-Stress Partially Accelerated Life Tests Under Multiple Censored Data

In this article, we present the performance of the maximum likelihood estimates of the Burr XII parameters for constant-stress partially accelerated life tests under multiple censored data. Two maximum likelihood estimation methods are considered. One method is based on observed-data likelihood function and the maximum likelihood estimates are obtained by using the quasi-Newton algorithm. The other method is based on complete-data likelihood function and the maximum likelihood estimates are derived by using the expectation-maximization (EM) algorithm. The variance–covariance matrices are derived to construct the confidence intervals of the parameters. The performance of these two algorithms is compared with each other by a simulation study. The simulation results show that the maximum likelihood estimation via the EM algorithm outperforms the quasi-Newton algorithm in terms of the absolute relative bias, the bias, the root mean square error and the coverage rate. Finally, a numerical example is given to illustrate the performance of the proposed methods.     

Design two-level factorial experiments in blocks of size four

Recently, many researchers have devoted themselves to the investigation on the number of replicates needed for experiments in blocks of size two. In practice, experiments in blocks of size four might be more useful than those in blocks of size two. To estimate the main effects and two-factor interactions from a two-level factorial experiment in blocks, we might need many replicates. This article investigates designs with the least number of replicates for factorial experiments in blocks of size four. The methods to obtain such designs are presented.     

Nonparametric methods in multivariate factorial designs for large number of factor levels

We propose different multivariate nonparametric tests for factorial designs and derive their asymptotic distribution for the situation where the number of replications is limited, whereas the number of treatments goes to infinity (large a, small n case). The tests are based on separate rankings for the different variables, and they are therefore invariant under separate monotone transformations of the individual variables.     

A survey and evaluation of methods for determination of combinatorial equivalence of factorial designs

Equivalent factorial designs have identical statistical properties for estimation of factorial contrasts and for model fitting. Non-equivalent designs, however, may have the same statistical properties under one particular model but different properties under a different model. In this paper, we describe known methods for the determination of equivalence or non-equivalence of two-level factorial designs, whether they be regular factorial designs, non-regular orthogonal arrays, or have no particular structure. In addition, we evaluate a number of potential fast screening methods for detecting non-equivalence of designs. Although the paper concentrates mainly on symmetric designs with factors at two levels, we also evaluate methods of determining combinatorial equivalence and non-equivalence of three-level designs and indicate extensions to larger numbers of levels and to asymmetric designs.     

Robust inference for bivariate point processes

In the analysis of recurrent events where the primary interest lies in studying covariate effects on the expected number of events occurring over a period of time, it is appealing to base models on the cumulative mean function (CMF) of the processes (Lawless & Nadeau 1995). In many chronic diseases, however, more than one type of event is manifested. Here we develop a robust inference procedure for joint regression models for the CMFs arising from a bivariate point process. Consistent parameter estimates with robust variance estimates are obtained via unbiased estimating functions for the CMFs. In most situations, the covariance structure of the bivariate point processes is difficult to specify correctly, but when it is known, an optimal estimating function for the CMFs can be obtained. As a convenient model for more general settings, we suggest the use of the estimating functions arising from bivariate mixed Poisson processes. Simulation studies demonstrate that the estimators based on this working model are practically unbiased with robust variance estimates. Furthermore, hypothesis tests may be based on the generalized Wald or generalized score tests. Data from a trial of patients with bronchial asthma are analyzed to illustrate the estimation and inference procedures.     

Experimentation order with good properties for 2 k factorial designs

Randomizing the order of experimentation in a factorial design does not always achieve the desired effect of neutralizing the influence of unknown factors. In fact, with some very reasonable assumptions, an important proportion of random orders achieve the same degree of protection as that obtained by experimenting in the design matrix standard order. In addition, randomization can induce a large number of changes in factor levels and thus make experimentation expensive and difficult. De Leon et al. [Experimentation order in factorial designs with 8 or 16 runs, J. Appl. Stat. 32 (2005), pp. 297–313] proposed experimentation orders for designs with eight or 16 runs that combine an excellent level of protection against the influence of unknown factors, with the minimum number of changes in factor levels. This article presents a new methodology to obtain experimentation orders with the desired properties for designs with any number of runs.     

Modified Robust Second-Order Slope-Rotatable Designs

Generally it is very difficult to construct robust slope-rotatable designs along axial directions. Present paper focuses on modified second-order slope-rotatable designs (SOSRDs) with correlated errors. Modified robust second-order slope-rotatability conditions are derived for a general variance–covariance structure of errors. These conditions get simplified for intraclass correlation structure. A few robust second-order slope-rotatable designs (over all directions, or with equal maximum directional variance slope, or D-optimal slope) are examined with respect to modified robust slope-rotatability. It is observed that robust second-order slope-rotatable designs over all directions, or with equal maximum directional variance slope, or D-optimal slope are not generally modified robust second-order slope-rotatable designs.     

ON OPTIMIZING MULTI-LEVEL DESIGNS: POWER UNDER BUDGET CONSTRAINTS

This paper derives a procedure for efficiently allocating the number of units in multi‐level designs given prespecified power levels. The derivation of the procedure is based on a constrained optimization problem that maximizes a general form of a ratio of expected mean squares subject to a budget constraint. The procedure makes use of variance component estimates to optimize designs during the budget formulating stages. The method provides more general closed form solutions than other currently available formulae. As such, the proposed procedure allows for the determination of the optimal numbers of units for studies that involve more complex designs. A method is also described for optimizing designs when variance component estimates are not available. Case studies are provided to demonstrate the method.     

On generalizations of the classical method of confounding to asymmetric factorial experiments

A Kronecker product structure is identified for a particular class of asymmetric factorial designs in blocks, including the classes of designs generated by several of the generalizations of the classical method in the literature. The Kronecker product structure is utilized to establish orthogonal factorial structure for the class of designs and to identify a Principle of Generalized Interaction.     

Clustering Effects in Unreplicated Factorial Experiments

The analysis of unreplicated factorial designs concentrates much attention since there are no degrees of freedom left to estimate the error variance. In this article, we propose clustering the factorial estimates in two groups, one containing the active effects and one containing the inactive effects. The powerfulness of the proposed method is revealed via a comparative simulation study.