Weighted Multiple Testing Correction for Correlated Binary Endpoints

Multiple binary endpoints often occur in clinical trials and are usually correlated. Many multiple testing adjustment methods have been proposed to control familywise type I error rates. However, most of them disregard the correlation among the endpoints, for example, the commonly used Bonferroni correction, Bonferroni fixed-sequence (BFS) procedure, and its extension, the alpha-exhaustive fallback (AEF). Extending BFS by taking into account correlations among endpoints, Huque and Alosh proposed a flexible fixed-sequence (FFS) testing method, but this FFS method faces computational difficulty when there are four or more endpoints and the power of the first hypothesis does not depend on the correlations among endpoints. In dealing with these issues, Xie proposed a weighted multiple testing correction (WMTC) for correlated continuous endpoints and showed that the proposed method can easily handle hundreds of endpoints by using the R package and has higher power for testing the first hypothesis compared with the FFS and AEF methods. Since WMTC depends on the joint distribution of the endpoints, it is not clear whether WMTC still keeps those advantages when correlated binary endpoints are used. In this article, we evaluated the statistical power of WMTC method for correlated binary endpoints in comparison with the FFS, the AEF, the prospective alpha allocation scheme (PAAS), and the weighted Holm-Bonferroni methods. Furthermore the WMTC method and others are illustrated on a real dataset examining the circumstance of homicide in New York City.     

Testing of a sub-hypothesis in linear regression models with long memory errors and deterministic design

This paper considers the problem of testing a sub-hypothesis in homoscedastic linear regression models where errors form long memory moving average processes and designs are non-random. Unlike in the random design case, asymptotic null distribution of the likelihood ratio type test based on the Whittle quadratic form is shown to be non-standard and non-chi-square. Moreover, the rate of consistency of the minimum Whittle dispersion estimator of the slope parameter vector is shown to be n^-(1-α)/2$n^{-(1-\alpha )/2}$, different from the rate n^-1/2$n^{-1/2}$ obtained in the random design case, where α$\alpha$ is the rate at which the error spectral density explodes at the origin. The proposed test is shown to be consistent against fixed alternatives and has non-trivial asymptotic power against local alternatives that converge to null hypothesis at the rate n^-(1-α)/2$n^{-(1-\alpha )/2}$.     

Isotonic L2-projection test for local monotonicity of a hazard

We introduce a test statistic for testing the null hypothesis that the sampling distribution has a strictly increasing hazard rate on a specified interval [a,b]$[a,b]$. It is based on a comparison of the empirical distribution function with a shape-constrained estimate, using the restriction that the hazard is increasing. Its asymptotic (normal) distribution was recently derived in Groeneboom and Jongbloed (submitted for publication). We discuss a bootstrap method for computing the critical values and compare the test, thus obtained, with other recently proposed methods in a simulation study. Moreover, we prove that the bootstrap method works asymptotically. In proving that the (smooth and isotonic) bootstrap method works, we derive some results that seem to be of independent interest.     

Goodness-of-fit tests for parametric regression with selection biased data

Consider the nonparametric location-scale regression model Y=m(X)+σ(X)ε$Y=m(X)+\sigma (X)\epsilon$, where the error ε$\epsilon$ is independent of the covariate X$X$, and m$m$ and σ$\sigma$ are smooth but unknown functions. The pair (X,Y)$(X,Y)$ is allowed to be subject to selection bias. We construct tests for the hypothesis that m(·)$m(·)$ belongs to some parametric family of regression functions. The proposed tests compare the nonparametric maximum likelihood estimator (NPMLE) based on the residuals obtained under the assumed parametric model, with the NPMLE based on the residuals obtained without using the parametric model assumption. The asymptotic distribution of the test statistics is obtained. A bootstrap procedure is proposed to approximate the critical values of the tests. Finally, the finite sample performance of the proposed tests is studied in a simulation study, and the developed tests are applied on environmental data.     

On the joint distribution of placement statistics under progressive censoring and applications to precedence test

In reliability and survival analysis, comparison of two or more populations is an important problem. For example, while comparing a treatment group with a control group, one may be interested in determining whether the observations in the treatment group have a longer lifetime than those from the control group, that is, whether the treatment is effective or not. In such a study, it would be extremely valuable to make a decision based on early failures. In this paper, we consider independent progressively Type-II censored random samples from two populations with cumulative distribution function's (cdf) F(·)$F(·)$ and G(·)$G(·)$ respectively, and discuss a precedence test for testing the equality of the two distributions based on placements. For this purpose, we derive the joint distribution of the first l   placement statistics from the progressively censored sample from F(·)$F(·)$. We then derive the exact null distribution of the precedence test statistic which is simply the sum of the placements. We provide the rejection regions for fixed levels of significance and various sample sizes and different progressive censoring schemes.     

Analysis of one-way layout of count data in the presence of over or under dispersion

This article develops test statistics for the homogeneity of the means of several treatment groups of count data in the presence of over-dispersion or under-dispersion when there is no likelihood available. The C(α)$C(\alpha )$ or score type tests based on the models that are specified by only the first two moments of the counts are obtained using quasi-likelihood, extended quasi-likelihood, and double extended quasi-likelihood. Monte Carlo simulations are then used to study the comparative behavior of these C(α)$C(\alpha )$ statistics compared to the C(α)$C(\alpha )$ statistic based on a parametric model, namely, the negative binomial model, in terms of the following: size; power; robustness for departures from the data distribution as well as dispersion homogeneity. These simulations demonstrate that the C(α)$C(\alpha )$ statistic based on the double extended quasi-likelihood holds the nominal size at the 5% level well in all data situations, and it shows some edge in power over the other statistics, and, in particular, it performs much better than the commonly used statistic based on the quasi-likelihood. This C(α)$C(\alpha )$ statistic also shows robustness for moderate heterogeneity due to dispersion. Finally, applications to ecological, toxicological and biological data are given.     

A fixed sequence Bonferroni procedure for testing multiple endpoints

A method for controlling the familywise error rate combining the Bonferroni adjustment and fixed testing sequence procedures is proposed. This procedure allots Type I error like the Bonferroni adjustment, but allows the Type I error to accumulate whenever a null hypothesis is rejected. In this manner, power for hypotheses tested later in a prespecified order will be increased. The order of the hypothesis tests needs to be prespecified as in a fixed sequence testing procedure, but unlike the fixed sequence testing procedure all hypotheses can always be tested, allowing for an a priori method of concluding a difference in the various endpoints. An application will be in clinical trials in which mortality is a concern, but it is expected that power to distinguish a difference in mortality will be low. If the effect on mortality is larger than anticipated, this method allows a test with a prespecified method of controlling the Type I error rate. Copyright © 2003 John Wiley & Sons, Ltd.     

Elicitation of multivariate prior distributions: A nonparametric Bayesian approach

In the context of Bayesian statistical analysis, elicitation is the process of formulating a prior density f(·)$f(·)$ about one or more uncertain quantities to represent a person's knowledge and beliefs. Several different methods of eliciting prior distributions for one unknown parameter have been proposed. However, there are relatively few methods for specifying a multivariate prior distribution and most are just applicable to specific classes of problems and/or based on restrictive conditions, such as independence of variables. Besides, many of these procedures require the elicitation of variances and correlations, and sometimes elicitation of hyperparameters which are difficult for experts to specify in practice. Garthwaite et al. (2005) discuss the different methods proposed in the literature and the difficulties of eliciting multivariate prior distributions. We describe a flexible method of eliciting multivariate prior distributions applicable to a wide class of practical problems. Our approach does not assume a parametric form for the unknown prior density f(·)$f(·)$, instead we use nonparametric Bayesian inference, modelling f(·)$f(·)$ by a Gaussian process prior distribution. The expert is then asked to specify certain summaries of his/her distribution, such as the mean, mode, marginal quantiles and a small number of joint probabilities. The analyst receives that information, treating it as a data set D   with which to update his/her prior beliefs to obtain the posterior distribution for f(·)$f(·)$. Theoretical properties of joint and marginal priors are derived and numerical illustrations to demonstrate our approach are given.     

Minimum Hellinger distance estimation in a nonparametric mixture model

In this paper, we investigate the estimation problem of the mixture proportion λ$\lambda$ in a nonparametric mixture model of the form λF(x)+(1-λ)G(x)$\lambda F(x)+(1-\lambda )G(x)$ using the minimum Hellinger distance approach, where F and G are two unknown distributions. We assume that data from the distributions F and G   as well as from the mixture distribution λF+(1-λ)G$\lambda F+(1-\lambda )G$ are available. We construct a minimum Hellinger distance estimator of λ$\lambda$ and study its asymptotic properties. The proposed estimator is chosen to minimize the Hellinger distance between a parametric mixture model and a nonparametric density estimator. We also develop a maximum likelihood estimator of λ$\lambda$. Theoretical properties such as the existence, strong consistency, asymptotic normality and asymptotic efficiency of the proposed estimators are investigated. Robustness properties of the proposed estimator are studied using a Monte Carlo study. Two real data examples are also analyzed.     

Rates of convergence for the k-nearest neighbor estimators with smoother regression functions

Let (X, Y  ) be a R^d×R-valued${\mathbb{R}}^d\times \mathbb{R}\mathrm{-}\mathrm{valued}$ random vector. In regression analysis one wants to estimate the regression function m(x)?E(Y|X=x)$m(x)?\mathbf{E}(Y|X=x)$ from a data set. In this paper we consider the rate of convergence for the k-nearest neighbor estimators in case that X   is uniformly distributed on [0,1]^d$[\mathrm{0,1}{]}^d$, Var(Y|X=x)$\mathbf{Var}(Y|X=x)$ is bounded, and m is (p, C)-smooth. It is an open problem whether the optimal rate can be achieved by a k  -nearest neighbor estimator for 1<p≤1.5$1<p\le 1.5$. We solve the problem affirmatively. This is the main result of this paper. Throughout this paper, we assume that the data is independent and identically distributed and as an error criterion we use the expected L₂ error.     

Super-simple cyclic designs with small values

Super-simple cyclic designs are useful on constructing codes and designs such as superimposed codes, perfect hash families and optical orthogonal codes with index two. In this paper, we show that there exists a super-simple cyclic (v,4,λ)$(v,4,\lambda )$ for 7?v?41$7?v?41$ and all admissible λ$\lambda$ with two definite exceptions of (v,λ)=(9,3),(13,5)$(v,\lambda )=(9,3),(13,5)$ and one possible exception of (v,λ)=(39,18)$(v,\lambda )=(39,18)$. Some useful algorithms are explained for computer search and new designs are displayed.     

Efficiency in estimation of memory

We study the efficiency of semiparametric estimates of memory parameter. We propose a class of shift invariant tapers of order (p,q). For a fixed p, the variance inflation factor of the new tapers approaches 1 as q   goes to infinity. We show that for d∈(−1/2,p+1/2)$d\in (-1/2,p+1/2)$, the proposed tapered Gaussian semiparametric estimator has the same limiting distribution as the nontapered version for d∈(−1/2,1/2)$d\in (-1/2,1/2)$. The new estimator is mean and polynomial trend invariant, and is computationally advantageous in comparison to the recently proposed exact local Whittle estimator. The simulation study shows that our estimator has comparable or better mean squared error in finite samples for a variety of models.     

Tools for constructing optimal two-level factorial designs for a linear model containing main effects and one two-factor interaction

In Hedayat and Pesotan [1992, Two-level factorial designs for main effects and selected two-factor interactions. Statist. Sinica 2, 453–464.] the concepts of a g(n,e)$g(n,e)$-design and a g(n,e)$g(n,e)$-matrix are introduced to study designs of n$n$ factor two-level experiments which can unbiasedly estimate the mean, the n$n$ main effects and e$e$ specified two-factor interactions appearing in an orthogonal polynomial model and it is observed that the construction of a g-design is equivalent to the construction of a g  -matrix. This paper deals with the construction of D-optimal g(n,1)$g(n,1)$-matrices. A standard form for a g(n,1)$g(n,1)$-matrix is introduced and some lower and upper bounds on the absolute determinant value of a D-optimal g(n,1)$g(n,1)$-matrix in the class of all g(n,1)$g(n,1)$-matrices are obtained and an approach to construct D-optimal g(n,1)$g(n,1)$-matrices is given for 2?n?8$2?n?8$. For two specific subclasses, namely a certain class of g(n,1)$g(n,1)$-matrices within the class of g(n,1)$g(n,1)$-matrices of index one and the class C(H)$C(H)$ of g(8t+2,1)$g(8t+2,1)$-matrices constructed from a normalized Hadamard matrix H   of order 8t+4(t?1)$8t+4(t?1)$ two techniques for the construction of the restricted D-optimal matrices are given.     

A marked point process perspective in fitting spatial point process models

This paper discusses a new perspective in fitting spatial point process models. Specifically the spatial point process of interest is treated as a marked point process where at each observed event x$\mathbf{x}$ a stochastic process M(x;t)$M(\mathbf{x};t)$, 0<t<r$0<t<r$, is defined. Each mark process M(x;t)$M(\mathbf{x};t)$ is compared with its expected value, say F(t;θ)$F(t;\theta )$, to produce a discrepancy measure at x$\mathbf{x}$, where θ$\theta$ is a set of unknown parameters. All individual discrepancy measures are combined to define an overall measure which will then be minimized to estimate the unknown parameters. The proposed approach can be easily applied to data with sample size commonly encountered in practice. Simulations and an application to a real data example demonstrate the efficacy of the proposed approach.     

Representing a function of two variables as a superposition over angles of ridge functions with a given shape via linear programming

A ridge function with shape function g   in the horizontal direction is a function of the form g(x)h(y,0)$g(x)h(y,0)$. Along each horizontal line it has the shape g(x)$g(x)$, multiplied by a function h(y,0)$h(y,0)$ which depends on the y-value of the horizontal line. Similarly a ridge function with shape function g   in the vertical direction has the form g(y)h(x,π/2)$g(y)h(x,\pi /2)$. For a given shape function g it may or may not be possible to represent an arbitrary   function f(x,y)$f(x,y)$ as a superposition over all angles of a ridge function with shape g   in each direction, where h=_hf=_hf,g$h=h_f=h_{f,g}$ depends on the functions f and g   and also on the direction, θ:h=_hf,g(·,θ)$\theta :h=h_{f,g}(·,\theta )$. We show that if g   is Gaussian centered at zero then this is always possible and we give the function _hf,g$h_{f,g}$ for a given f(x,y)$f(x,y)$. For highpass or for odd shapes g  , we show it is impossible to represent an arbitrary f(x,y)$f(x,y)$, i.e. in general there is no _hf,g$h_{f,g}$. Note that our problem is similar to tomography, where the problem is to invert the Radon transform, except that the use of the word inversion is here somewhat “inverted”: in tomography f(x,y)$f(x,y)$ is unknown and we find it by inverting the projections of f  ; here, f(x,y)$f(x,y)$ is known, g(z)$g(z)$ is known, and _hf(·,θ)=_hf,g(·,θ)$h_f(·,\theta )=h_{f,g}(·,\theta )$ is the unknown.     

Classification of orthogonal arrays by integer programming

The problem of classifying all isomorphism classes of OA(N,k,s,t)$\mathrm{OA}(N,k,s,t)$'s is shown to be equivalent to finding all isomorphism classes of non-negative integer solutions to a system of linear equations under the symmetry group of the system of equations. A branch-and-cut algorithm developed by Margot [2002. Pruning by isomorphism in branch-and-cut. Math. Programming Ser. A 94, 71–90; 2003a. Exploiting orbits in symmetric ILP. Math. Programming Ser. B 98, 3–21; 2003b. Small covering designs by branch-and-cut. Math. Programming Ser. B 94, 207–220; 2007. Symmetric ILP: coloring and small integers. Discrete Optim., 4, 40–62] for solving integer programming problems with large symmetry groups is used to find all non-isomorphic OA(24,7,2,2)$\mathrm{OA}(24,7,2,2)$'s, OA(24,k,2,3)$\mathrm{OA}(24,k,2,3)$'s for 6?k?11$6?k?11$, OA(32,k,2,3)$\mathrm{OA}(32,k,2,3)$'s for 6?k?11$6?k?11$, OA(40,k,2,3)$\mathrm{OA}(40,k,2,3)$'s for 6?k?10$6?k?10$, OA(48,k,2,3)$\mathrm{OA}(48,k,2,3)$'s for 6?k?8$6?k?8$, OA(56,k,2,3)$\mathrm{OA}(56,k,2,3)$'s, OA(80,k,2,4)$\mathrm{OA}(80,k,2,4)$'s, OA(112,k,2,4)$\mathrm{OA}(112,k,2,4)$'s, for k=6,7$k=6,7$, OA(64,k,2,4)$\mathrm{OA}(64,k,2,4)$'s, OA(96,k,2,4)$\mathrm{OA}(96,k,2,4)$'s for k=7,8$k=7,8$, and OA(144,k,2,4)$\mathrm{OA}(144,k,2,4)$'s for k=8,9$k=8,9$. Further applications to classifying covering arrays with the minimum number of runs and packing arrays with the maximum number of runs are presented.