Multivariate tests comparing binomial probabilities, with application to safety studies for drugs

Summary.  In magazine advertisements for new drugs, it is common to see summary tables that compare the relative frequency of several side-effects for the drug and for a placebo, based on results from placebo-controlled clinical trials. The paper summarizes ways to conduct a global test of equality of the population proportions for the drug and the vector of population proportions for the placebo. For multivariate normal responses, the Hotelling T ²-test is a well-known method for testing equality of a vector of means for two independent samples. The tests in the paper are analogues of this test for vectors of binary responses. The likelihood ratio tests can be computationally intensive or have poor asymptotic performance. Simple quadratic forms comparing the two vectors provide alternative tests. Much better performance results from using a score-type version with a null-estimated covariance matrix than from the sample covariance matrix that applies with an ordinary Wald test. For either type of statistic, asymptotic inference is often inadequate, so we also present alternative, exact permutation tests. Follow-up inferences are also discussed, and our methods are applied to safety data from a phase II clinical trial.     

极坐标中平衡微分方程通解的直接推导方法

从极坐标下应力分量是ｒ、θ的连续函数出发，假设某一应力分量是某一函数对ｒ或对θ的偏导数，找到了直接推导极坐标下不计体力时平衡微分方程通解的途径，给出了两种推导方法，均比惯常的方法简捷直观，从而证明了直接推导应力函数是可行的．     

Delay Estimation for Some Stationary Diffusion-type Processes

In this paper the asymptotic behaviour of the maximum likelihood and Bayesian estimators of a delay parameter is studied. The observed process is supposed to be the solution of a linear stochastic differential equation with one time delay term. It is shown that these estimators are consistent and their limit distributions are described. The behaviour of the estimators is similar to the behaviour of corresponding estimators in change-point problems. The question of asymptotical efficiency is also discussed.     

一类平衡阶数为负整数的非线性偏微分方程的精确解

以齐次平衡原理为基础,给出了平衡阶数为负整数时的求解非线性偏微分方程的基本方法,并对方程ut=αuuxx+βu2x+p(u-u2)进行求解,到得了它的两个不同形式的精确解。     

On repeated measures analysis with misspecified covariance structure

In recent years various sophisticated methods have been developed for the analysis of repeated measures, or longitudinal data. The more traditional approach, based on a normal likelihood function, has been shown to be unsatisfactory, in the sense of yielding asymptotically biased estimates when the covariance structure is misspecified. More recent methodology, based on generalized linear models and quasi-likelihood estimation, has gained widespread acceptance as 'generalized estimating equations'. However, this also has theoretical problems. In this paper a suggestion is made for improving the asymptotic behaviour of estimators by using the older approach, implemented via Gaussian estimation. The resulting estimating equations include the quasi-score function as one component, so the methodology proposed can be viewed as a combination of Gaussian estimation and generalized estimating equations which has a firmer asymptotic basis than either alone has.     

Modelling heterogeneity in longitudinal binomial responses by generalized estimating equations

ABSTRACT

Extra-binomial variation in longitudinal/clustered binomial data is frequently observed in biomedical and observational studies. The usual generalized estimating equations method treats the extra-binomial parameter as a constant across all subjects. In this paper, a two-parameter variance function modelling the extraneous variance is proposed to account for heterogeneity among subjects. The new approach allows modelling the extra-binomial variation as a function of the mean and binomial size.     

Two-step and likelihood methods for HIV viral dynamic models with covariate measurement errors and missing data

HIV viral dynamic models have received much attention in the literature. Long-term viral dynamics may be modelled by semiparametric nonlinear mixed-effect models, which incorporate large variation between subjects and autocorrelation within subjects and are flexible in modelling complex viral load trajectories. Time-dependent covariates may be introduced in the dynamic models to partially explain the between-individual variations. In the presence of measurement errors and missing data in time-dependent covariates, we show that the commonly used two-step method may give approximately unbiased estimates but may under-estimate standard errors. We propose a two-stage bootstrap method to adjust the standard errors in the two-step method and a likelihood method.     

Instrument endogeneity and identification-robust tests: Some analytical results

When some explanatory variables in a regression are correlated with the disturbance term, instrumental variable methods are typically employed to make reliable inferences. Furthermore, to avoid difficulties associated with weak instruments, identification-robust methods are often proposed. However, it is hard to assess whether an instrumental variable is valid in practice because instrument validity is based on the questionable assumption that some of them are exogenous. In this paper, we focus on structural models and analyze the effects of instrument endogeneity on two identification-robust procedures, the Anderson–Rubin (1949, AR) and the Kleibergen (2002, K) tests, with or without weak instruments. Two main setups are considered: (1) the level of “instrument” endogeneity is fixed (does not depend on the sample size) and (2) the instruments are locally exogenous, i.e. the parameter which controls instrument endogeneity approaches zero as the sample size increases. In the first setup, we show that both test procedures are in general consistent against the presence of invalid instruments (hence asymptotically invalid for the hypothesis of interest), whether the instruments are “strong” or “weak”. We also describe cases where test consistency may not hold, but the asymptotic distribution is modified in a way that would lead to size distortions in large samples. These include, in particular, cases where the 2SLS estimator remains consistent, but the AR and K tests are asymptotically invalid. In the second setup, we find (non-degenerate) asymptotic non-central chi-square distributions in all cases, and describe cases where the non-centrality parameter is zero and the asymptotic distribution remains the same as in the case of valid instruments (despite the presence of invalid instruments). Overall, our results underscore the importance of checking for the presence of possibly invalid instruments when applying “identification-robust” tests.     

高阶中立型时滞微分方程的渐近性与振动性

得到了变系数高阶中立型时滞微分方程d^n/d^tn[x(t) p(t)x(t-τ)] ∑i=1^mQi(t)(t-бi)=0的渐近性和n为偶数时解振动的充分性判据。改进和推广了文献^[1-4]中的结果。     

一类差分方程的回归点集

本文讨论了周期点的周期为2的方幂的一类差分方程的回归点的性质,定义这类差分方程的第i个分量仅依赖于前面i个独立变量