An application of multinomial logistic regression to estimating performance of a multiple-screening test with incomplete verification

Summary.  The paper describes a method of estimating the performance of a multiple-screening test where those who test negatively do not have their true disease status determined. The methodology is motivated by a data set on 49927 subjects who were given K =6 binary tests for bowel cancer. A complicating factor is that individuals may have polyps in the bowel, a condition that the screening test is not designed to detect but which may be worth diagnosing. The methodology is based on a multinomial logit model for Pr( S | R ₆), the probability distribution of patient status S (healthy, polyps or diseased) conditional on the results R ₆ from six binary tests. An advantage of the methodology described is that the modelling is data driven. In particular, we require no assumptions about correlation within subjects, the relative sensitivity of the K tests or the conditional independence of the tests. The model leads to simple estimates of the trade-off between different errors as the number of tests is varied, presented graphically by using receiver operating characteristic curves. Finally, the model allows us to estimate better protocols for assigning subjects to the disease group, as well as the gains in accuracy from these protocols.     

ESTIMATING THE FALSE NEGATIVE FRACTION FOR A MULTIPLE SCREENING TEST FOR BOWEL CANCER WHEN NEGATIVES ARE NOT VERIFIED

This paper aims to estimate the false negative fraction of a multiple screening test for bowel cancer, where those who give negative results for six consecutive tests do not have their true disease status verified. A subset of these same individuals is given a further screening test, for the sole purpose of evaluating the accuracy of the primary test. This paper proposes a beta heterogeneity model for the probability of a diseased individual ‘testing positive’ on any single test, and it examines the consequences of this model for inference on the false negative fraction. The method can be generalized to the case where selection for further testing is informative, though this did not appear to be the case for the bowel‐cancer data.     

Modified quasi-profile likelihoods from estimating functions

We discuss higher-order adjustments for a quasi-profile likelihood for a scalar parameter of interest, in order to alleviate some of the problems inherent to the presence of nuisance parameters, such as bias and inconsistency. Indeed, quasi-profile score functions for the parameter of interest have bias of order O(1)$\mathrm{O}(1)$, and such bias can lead to poor inference on the parameter of interest. The higher-order adjustments are obtained so that the adjusted quasi-profile score estimating function is unbiased and its variance is the negative expected derivative matrix of the adjusted profile estimating equation. The modified quasi-profile likelihood is then obtained as the integral of the adjusted profile estimating function. We discuss two methods for the computation of the modified quasi-profile likelihoods: a bootstrap simulation method and a first-order asymptotic expression, which can be simplified under an orthogonality assumption. Examples in the context of generalized linear models and of robust inference are provided, showing that the use of a modified quasi-profile likelihood ratio statistic may lead to coverage probabilities more accurate than those pertaining to first-order Wald-type confidence intervals.     

Repeated screening with inspection error and no false positive results with application to pharmaceutical pill production

Summary.  Repeated screening is a 100% sampling inspection of a batch of items followed by removal of the defective items and further iterations of inspection and removal. The reason for repeating the inspection is that the detection of a defective item happens with probability p <1. A missed defective item is a false negative result. The no false positive result is contemplated in this paper, which is motivated by a problem coming from the production of pharmaceutical pills. Bayesian posterior distributions for the quality of the lot are obtained for the case of both p known and p unknown. Batch rejection and batch acceptance control limits for the number of defective items at subsequent iterations can then be calculated. Theoretical connections to the problem of estimating the number-of-trials parameter of a binomial distribution are drawn.     

Estimation of Sib–Sib Correlation via a Kotz-Type Density Function

We estimate sib–sib correlation by maximizing the log-likelihood of a Kotz-type distribution. Using extensive simulations we conclude that estimating sib–sib correlation using the proposed method has many advantages. Results are illustrated on a real life data set due to Galton. Testing of hypothesis about this correlation is also discussed using the three likelihood based tests and a test based on Srivastava's estimator. It is concluded that score test derived using Kotz-type density performs the best.     

Vector autoregressive models with measurement errors for testing Granger causality

This paper develops a method for estimating the parameters of a vector autoregression (VAR) observed in white noise. The estimation method assumes that the noise variance matrix is known and does not require any iterative process. This study provides consistent estimators and the asymptotic distribution of the parameters required for conducting tests of Granger causality. Methods in the existing statistical literature cannot be used for testing Granger causality, since under the null hypothesis the model becomes unidentifiable. Measurement error effects on parameter estimates were evaluated by using computational simulations. The results suggest that the proposed approach produces empirical false positive rates close to the adopted nominal level (even for small samples) and has a satisfactory performance around the null hypothesis. The applicability and usefulness of the proposed approach are illustrated using a functional magnetic resonance imaging dataset.     

Semi-parametric modelling and likelihood estimation with estimating equations

This paper proposes a semi-parametric modelling and estimating method for analysing censored survival data. The proposed method uses the empirical likelihood function to describe the information in data, and formulates estimating equations to incorporate knowledge of the underlying distribution and regression structure. The method is more flexible than the traditional methods such as the parametric maximum likelihood estimation (MLE), Cox's (1972) proportional hazards model, accelerated life test model, quasi-likelihood (Wedderburn, 1974) and generalized estimating equations (Liang & Zeger, 1986). This paper shows the existence and uniqueness of the proposed semi-parametric maximum likelihood estimates (SMLE) with estimating equations. The method is validated with known cases studied in the literature. Several finite sample simulation and large sample efficiency studies indicate that when the sample size is larger than 100 the SMLE is compatible with the parametric MLE; and in all case studies, the SMLE is about 15% better than the parametric MLE with a mis-specified underlying distribution.     

Choosing between per-genotype,per-allele,and trend approaches for initial detection of gene–disease association

There are a number of approaches to detect candidate gene–disease associations including: (i) ‘per-genotype’, which looks for any difference across the genotype groups without making any assumptions about the direction of the effect or the genetic model; (ii) ‘per-allele’, which assumes an additive genetic model, i.e. an effect for each allele copy; and (iii) linear trend, which looks for an incremental effect across the genotype groups. We simulated a number of gene–disease associations, varying odds ratios, allele frequency, genetic model, and deviation from Hardy–Weinberg equilibrium (HWE) and tested the performance of each of the three methods to detect the associations, where performance was judged by looking at critical values, power, coverage, bias, and root mean square error. Results indicate that the per-allele method is very susceptible to false positives and false negatives when deviations from HWE occur. The linear trend test appears to have the best power under most simulated scenarios, but can sometimes be biased and have poor coverage. These results indicate that of these strategies a linear trend test may be best for initially testing an association, and the per-genotype approach may be best for estimating the magnitude of the association.     

On the Run Length of a State-Space Control Chart for Multivariate Autocorrelated Data

The literature on statistical process control (SPC) describes the negative effects of autocorrelation in terms of the increase in false alarms. This has been treated by the individual modeling of each series or the application of VAR models. In the former case, the analysis of the cross correlation structure between the variables is altered. In the latter, if the cross correlation is not strong, the filtering process may modify the weakest relations. In order to improve these aspects, state-space models have been introduced in multivariate statistical process control (MSPC). This article presents a proposal for building a control chart for innovations, estimating its average run length to highlight its advantages over the VAR approach mentioned above.     

On a new family of shifted logarithmic transformations

Most parametric statistical methods are based on a set of assumptions: normality, linearity and homoscedasticity. Transformation of a metric response is a popular method to meet these assumptions. In particular, transformation of the response of a linear model is a popular method when attempting to satisfy the Gaussian assumptions on the error components in the model. A particular problem with common transformations such as the logarithm or the Box–Cox family is that negative and zero data values cannot be transformed. This paper proposes a new transformation which allows negative and zero data values. The method for estimating the transformation parameter consider an objective criteria based on kurtosis and skewness for achieving normality. Use of the new transformation and the method for estimating the transformation parameter are illustrated with three data sets.     

基尼加权回归分析：概念、方法及应用

普通最小二乘法是进行回归分析最常用的基本方法,但该方法要求满足若干经典假设,对于小样本或在与收入相关回归分析的参数估计中易受奇异值、高收入群体的影响。本文试图利用基尼加权回归弥补以上不足。基尼加权回归可分为参数方法与非参数方法两类,参数方法基于样本残差的基尼平均差最小原则对参数进行估计;非参数方法则是直接由两点间的斜率加权得到。基尼加权回归分析可以进行参数假设检验并定义拟合优度,其中的假设检验在实际应用中采用Jackknife重抽样方法估计方差。文中提出的样本拓展基尼平均差算法,弥补了现有算法对样本数据只能提供近似计算的不足,极大简化相应的计算公式。利用我国2015年省域截面数据、1994至2015年总量时间序列数据分别讨论入境旅游收入对收入基尼系数的影响,发现使用基尼加权回归的结果不仅符合理论预期,而且可以通过不平等厌恶参数的变化反映入境旅游收入对不同群体收入公平性的影响。     

Statistical Inference Based on Pooled Data: A Moment-Based Estimating Equation Approach

We consider statistical inference on parameters of a distribution when only pooled data are observed. A moment-based estimating equation approach is proposed to deal with situations where likelihood functions based on pooled data are difficult to work with. We outline the method to obtain estimates and test statistics of the parameters of interest in the general setting. We demonstrate the approach on the family of distributions generated by the Box-Cox transformation model, and, in the process, construct tests for goodness of fit based on the pooled data.     

Evaluating surrogate variables for improving microarray multiple testing inference

The use of surrogate variables has been proposed as a means to capture, for a given observed set of data, sources driving the dependency structure among high-dimensional sets of features and remove the effects of those sources and their potential negative impact on simultaneous inference. In this article we illustrate the potential effects of latent variables on testing dependence and the resulting impact on multiple inference, we briefly review the method of surrogate variable analysis proposed by Leek and Storey (PNAS 2008; 105:18718-18723), and assess that method via simulations intended to mimic the complexity of feature dependence observed in real-world microarray data. The method is also assessed via application to a recent Merck microarray data set. Both simulation and case study results indicate that surrogate variable analysis can offer a viable strategy for tackling the multiple testing dependence problem when the features follow a potentially complex correlation structure, yielding improvements in the variability of false positive rates and increases in power.     

Simplified Estimating Functions for Diffusion Models with a High-dimensional Parameter

We consider estimating functions for discretely observed diffusion processes of the following type: for one part of the parameter of interest we propose to use a simple and explicit estimating function of the type studied by Kessler (2000); for the remaining part of the parameter we use a martingale estimating function. Such an approach is particularly useful in practical applications when the parameter is high-dimensional. It is also often necessary to supplement a simple estimating function by another type of estimating function because only the part of the parameter on which the invariant measure depends can be estimated by a simple estimating function. Under regularity conditions the resulting estimators are consistent and asymptotically normal. Several examples are considered in order to demonstrate the idea of the estimating procedure. The method is applied to two data sets comprising wind velocities and stock prices. In one example we also propose a general method for constructing diffusion models with a prescribed marginal distribution which have a flexible dependence structure.     

A semi-parametric method for estimating the beta coefficients of the hidden two-sided asset return jumps

ABSTRACT

We introduce a new methodology for estimating the parameters of a two-sided jump model, which aims at decomposing the daily stock return evolution into (unobservable) positive and negative jumps as well as Brownian noise. The parameters of interest are the jump beta coefficients which measure the influence of the market jumps on the stock returns, and are latent components. For this purpose, at first we use the Variance Gamma (VG) distribution which is frequently used in modeling financial time series and leads to the revelation of the hidden market jumps' distributions. Then, our method is based on the central moments of the stock returns for estimating the parameters of the model. It is proved that the proposed method provides always a solution in terms of the jump beta coefficients. We thus achieve a semi-parametric fit to the empirical data. The methodology itself serves as a criterion to test the fit of any sets of parameters to the empirical returns. The analysis is applied to NASDAQ and Google returns during the 2006–2008 period.     

Bayesian hierarchical model for the prediction of football results

The problem of modelling football data has become increasingly popular in the last few years and many different models have been proposed with the aim of estimating the characteristics that bring a team to lose or win a game, or to predict the score of a particular match. We propose a Bayesian hierarchical model to fulfil both these aims and test its predictive strength based on data about the Italian Serie A 1991–1992 championship. To overcome the issue of overshrinkage produced by the Bayesian hierarchical model, we specify a more complex mixture model that results in a better fit to the observed data. We test its performance using an example of the Italian Serie A 2007–2008 championship.     

False Discovery Rate Control With Groups

In the context of large-scale multiple hypothesis testing, the hypotheses often possess certain group structures based on additional information such as Gene Ontology in gene expression data and phenotypes in genome-wide association studies. It is hence desirable to incorporate such information when dealing with multiplicity problems to increase statistical power. In this article, we demonstrate the benefit of considering group structure by presenting a p-value weighting procedure which utilizes the relative importance of each group while controlling the false discovery rate under weak conditions. The procedure is easy to implement and shown to be more powerful than the classical Benjamini-Hochberg procedure in both theoretical and simulation studies. By estimating the proportion of true null hypotheses, the data-driven procedure controls the false discovery rate asymptotically. Our analysis on one breast cancer dataset confirms that the procedure performs favorably compared with the classical method.     

Missing values: sparse inverse covariance estimation and?an?extension to sparse regression

We propose an ℓ ₁-regularized likelihood method for estimating the inverse covariance matrix in the high-dimensional multivariate normal model in presence of missing data. Our method is based on the assumption that the data are missing at random (MAR) which entails also the completely missing at random case. The implementation of the method is non-trivial as the observed negative log-likelihood generally is a complicated and non-convex function. We propose an efficient EM algorithm for optimization with provable numerical convergence properties. Furthermore, we extend the methodology to handle missing values in a sparse regression context. We demonstrate both methods on simulated and real data.     

OPTIMAL TESTS OF SIGNIFICANCE

To perform a test of significance of a null hypothesis, a test statistic is chosen which is expected to be small if the hypothesis is false. Then the significance level of the test for an observed sample is the probability that the test statistic, under the assumptions of the hypothesis, is as small, or smaller than, its observed value. A "good" test statistic is taken to be one which is stochastically small when the null hypothesis is false. Optimal test statistics are defined using this criterion and the relationship of these methods to the Neyman-Pearson theory of hypothesis testing is considered.     

A Bayesian approach to sequential analysis in post‐licensure vaccine safety surveillance

With rapid development of computing technology, Bayesian statistics have increasingly gained more attention in various areas of public health. However, the full potential of Bayesian sequential methods applied to vaccine safety surveillance has not yet been realized, despite acknowledged practical benefits and philosophical advantages of Bayesian statistics. In this paper, we describe how sequential analysis can be performed in a Bayesian paradigm in the field of vaccine safety. We compared the performance of the frequentist sequential method, specifically, Maximized Sequential Probability Ratio Test (MaxSPRT), and a Bayesian sequential method using simulations and a real world vaccine safety example. The performance is evaluated using three metrics: false positive rate, false negative rate, and average earliest time to signal. Depending on the background rate of adverse events, the Bayesian sequential method could significantly improve the false negative rate and decrease the earliest time to signal. We consider the proposed Bayesian sequential approach to be a promising alternative for vaccine safety surveillance.