A simple method for estimating a regression model for κ between a pair of raters

Agreement studies commonly occur in medical research, for example, in the review of X-rays by radiologists, blood tests by a panel of pathologists and the evaluation of psychopathology by a panel of raters. In these studies, often two observers rate the same subject for some characteristic with a discrete number of levels. The κ-coefficient is a popular measure of agreement between the two raters. The κ-coefficient may depend on covariates, i.e. characteristics of the raters and/or the subjects being rated. Our research was motivated by two agreement problems. The first is a study of agreement between a pastor and a co-ordinator of Christian education on whether they feel that the congregation puts enough emphasis on encouraging members to work for social justice (yes versus no). We wish to model the κ-coefficient as a function of covariates such as political orientation (liberal versus conservative) of the pastor and co-ordinator. The second example is a spousal education study, in which we wish to model the κ-coefficient as a function of covariates such as the highest degree of the father of the wife and the father of the husband. We propose a simple method to estimate the regression model for the κ-coefficient, which consists of two logistic (or multinomial logistic) regressions and one linear regression for binary data. The estimates can be easily obtained in any generalized linear model software program.     

A monte carlo study of variable selection and inferences in a two stage random coefficient linear regression model with unbalanced data

A growth curve analysis is often applied to estimate patterns of changes in a given characteristic of different individuals. It is also used to find out if the variations in the growth rates among individuals are due to effects of certain covariates. In this paper, a random coefficient linear regression model, as a special case of the growth curve analysis, is generalized to accommodate the situation where the set of influential covariates is not known a priori. Two different approaches for seleaing influential covariates (a weighted stepwise selection procedure and a modified version of Rao and Wu’s selection criterion) for the random slope coefficient of a linear regression model with unbalanced data are proposed. Performances of these methods are evaluated by means of Monte-Carlo simulation. In addition, several methods (Maximum Likelihood, Restricted Maximum Likelihood, Pseudo Maximum Likelihood and Method of Moments) for estimating the parameters of the selected model are compared Proposed variable selection schemes and estimators are appliedtotheactualindustrial problem which motivated this investigation.     

Behavior of agreement measures in the presence of zero cells and biased marginal distributions

Kappa and B assess agreement between two observers independently classifying N units into k categories. We study their behavior under zero cells in the contingency table and unbalanced asymmetric marginal distributions. Zero cells arise when a cross-classification is never endorsed by both observers; biased marginal distributions occur when some categories are preferred differently between the observers. Simulations studied the distributions of the unweighted and weighted statistics for k=4, under fixed proportions of diagonal agreement and different patterns off-diagonal, with various sample sizes, and under various zero cell count scenarios. Marginal distributions were first uniform and homogeneous, and then unbalanced asymmetric distributions. Results for unweighted kappa and B statistics were comparable to work of Muñoz and Bangdiwala, even with zero cells. A slight increased variation was observed as the sample size decreased. Weighted statistics did show greater variation as the number of zero cells increased, with weighted kappa increasing substantially more than weighted B. Under biased marginal distributions, weighted kappa with Cicchetti weights were higher than with squared weights. Both statistics for observer agreement behaved well under zero cells. The weighted B was less variable than the weighted kappa under similar circumstances and different weights. In general, B's performance and graphical interpretation make it preferable to kappa under the studied scenarios.     

Least squares estimation of varying‐coefficient hazard regression with application to breast cancer dose‐intensity data

To enhance modeling flexibility, the authors propose a nonparametric hazard regression model, for which the ordinary and weighted least squares estimation and inference procedures are studied. The proposed model does not assume any parametric specifications on the covariate effects, which is suitable for exploring the nonlinear interactions between covariates, time and some exposure variable. The authors propose the local ordinary and weighted least squares estimators for the varying‐coefficient functions and establish the corresponding asymptotic normality properties. Simulation studies are conducted to empirically examine the finite‐sample performance of the new methods, and a real data example from a recent breast cancer study is used as an illustration. The Canadian Journal of Statistics 37: 659–674; 2009 © 2009 Statistical Society of Canada     

Nonparametric Modeling Auxiliary Covariates in Random Coefficient Models

Random coefficient model (RCM) is a powerful statistical tool in analyzing correlated data collected from studies with different clusters or from longitudinal studies. In practice, there is a need for statistical methods that allow biomedical researchers to adjust for the measured and unmeasured covariates that might affect the regression model. This article studies two nonparametric methods dealing with auxiliary covariate data in linear random coefficient models. We demonstrate how to estimate the coefficients of the models and how to predict the random effects when the covariates are missing or mismeasured. We employ empirical estimator and kernel smoother to handle a discrete and continuous auxiliary, respectively. Simulation results show that the proposed methods perform better than an alternative method that only uses data in the validation data set and ignores the random effects in the random coefficient model.     

Estimating the reliability of repeatedly measured endpoints based on linear mixed‐effects models. A tutorial

There are various settings in which researchers are interested in the assessment of the correlation between repeated measurements that are taken within the same subject (i.e., reliability). For example, the same rating scale may be used to assess the symptom severity of the same patients by multiple physicians, or the same outcome may be measured repeatedly over time in the same patients. Reliability can be estimated in various ways, for example, using the classical Pearson correlation or the intra‐class correlation in clustered data. However, contemporary data often have a complex structure that goes well beyond the restrictive assumptions that are needed with the more conventional methods to estimate reliability. In the current paper, we propose a general and flexible modeling approach that allows for the derivation of reliability estimates, standard errors, and confidence intervals – appropriately taking hierarchies and covariates in the data into account. Our methodology is developed for continuous outcomes together with covariates of an arbitrary type. The methodology is illustrated in a case study, and a Web Appendix is provided which details the computations using the R package CorrMixed and the SAS software. Copyright © 2016 John Wiley & Sons, Ltd.     

Incomplete covariates in the Cox model with applications to biological marker data

A common occurrence in clinical trials with a survival end point is missing covariate data. With ignorably missing covariate data, Lipsitz and Ibrahim proposed a set of estimating equations to estimate the parameters of Cox's proportional hazards model. They proposed to obtain parameter estimates via a Monte Carlo EM algorithm. We extend those results to non-ignorably missing covariate data. We present a clinical trials example with three partially observed laboratory markers which are used as covariates to predict survival.     

Semiparametric Quantile Regression Analysis of Right‐censored and Length‐biased Failure Time Data with Partially Linear Varying Effects

Right‐censored and length‐biased failure time data arise in many fields including cross‐sectional prevalent cohort studies, and their analysis has recently attracted a great deal of attention. It is well‐known that for regression analysis of failure time data, two commonly used approaches are hazard‐based and quantile‐based procedures, and most of the existing methods are the hazard‐based ones. In this paper, we consider quantile regression analysis of right‐censored and length‐biased data and present a semiparametric varying‐coefficient partially linear model. For estimation of regression parameters, a three‐stage procedure that makes use of the inverse probability weighted technique is developed, and the asymptotic properties of the resulting estimators are established. In addition, the approach allows the dependence of the censoring variable on covariates, while most of the existing methods assume the independence between censoring variables and covariates. A simulation study is conducted and suggests that the proposed approach works well in practical situations. Also, an illustrative example is provided.     

Causal inference in outcome-dependent two-phase sampling designs

Summary.  We consider estimation of the causal effect of a treatment on an outcome from observational data collected in two phases. In the first phase, a simple random sample of individuals is drawn from a population. On these individuals, information is obtained on treatment, outcome and a few low dimensional covariates. These individuals are then stratified according to these factors. In the second phase, a random subsample of individuals is drawn from each stratum, with known stratum-specific selection probabilities. On these individuals, a rich set of covariates is collected. In this setting, we introduce five estimators: simple inverse weighted; simple doubly robust; enriched inverse weighted; enriched doubly robust; locally efficient. We evaluate the finite sample performance of these estimators in a simulation study. We also use our methodology to estimate the causal effect of trauma care on in-hospital mortality by using data from the National Study of Cost and Outcomes of Trauma.     

Optimal rank set sampling estimates for a population proportion

This paper examines two different classes of estimates for a population proportion based on an unbalanced rank set sample. Specifically, the two classes correspond to the maximum likelihood estimator (MLE) and a weighted average (WA) estimate. Both estimators are asymptotically normal, so standard inference procedures can still be implemented. Furthermore, these results can be used to develop optimal allocation schemes for both estimators. The performances of the optimal estimators are studied in terms of both finite sample and asymptotic relative efficiency. In general, the MLE is more efficient than the WA estimate. Lastly, the practicality of the optimal sampling plans is addressed and illustrated via an example.     

A Class of Weighted Estimating Equations for Semiparametric Transformation Models with Missing Covariates

In survival analysis, covariate measurements often contain missing observations; ignoring this feature can lead to invalid inference. We propose a class of weighted estimating equations for right‐censored data with missing covariates under semiparametric transformation models. Time‐specific and subject‐specific weights are accommodated in the formulation of the weighted estimating equations. We establish unified results for estimating missingness probabilities that cover both parametric and non‐parametric modelling schemes. To improve estimation efficiency, the weighted estimating equations are augmented by a new set of unbiased estimating equations. The resultant estimator has the so‐called ‘double robustness’ property and is optimal within a class of consistent estimators.     

The weighted least square based estimators with censoring indicators missing at random

In this paper, we study linear regression analysis when some of the censoring indicators are missing at random. We define regression calibration estimate, imputation estimate and inverse probability weighted estimate for the regression coefficient vector based on the weighted least squared approach due to Stute (1993), and prove all the estimators are asymptotically normal. A simulation study was conducted to evaluate the finite properties of the proposed estimators, and a real data example is provided to illustrate our methods.     

INCOMPLETE DATA IN GENERALIZED LINEAR MODELS WITH CONTINUOUS COVARIATES

This paper proposes a method for estimating the parameters in a generalized linear model with missing covariates. The missing covariates are assumed to come from a continuous distribution, and are assumed to be missing at random. In particular, Gaussian quadrature methods are used on the E-step of the EM algorithm, leading to an approximate EM algorithm. The parameters are then estimated using the weighted EM procedure given in Ibrahim (1990). This approximate EM procedure leads to approximate maximum likelihood estimates, whose standard errors and asymptotic properties are given. The proposed procedure is illustrated on a data set.     

A new distribution-free k-sample test: Analysis of kernel density functionals

A novel distribution-free k-sample test of differences in location shifts based on the analysis of kernel density functional estimation is introduced and studied. The proposed test parallels one-way analysis of variance and the Kruskal–Wallis (KW) test aiming at testing locations of unknown distributions. In contrast to the rank (score)-transformed non-parametric approach, such as the KW test, the proposed F-test uses the measurement responses along with well-known kernel density estimation (KDE) to estimate the locations and construct the test statistic. A practical optimal bandwidth selection procedure is also provided. Our simulation studies and real data example indicate that the proposed analysis of kernel density functional estimate (ANDFE) test is superior to existing competitors for fat-tailed or heavy-tailed distributions when the k groups differ mainly in location rather than shape, especially with unbalanced data. ANDFE is also highly recommended when it is unclear whether test groups differ mainly in shape or location. The Canadian Journal of Statistics 48: 167–186; 2020 © 2019 Statistical Society of Canada     

Calculating power for the comparison of dependent κ-coefficients

Summary. In the psychosocial and medical sciences, some studies are designed to assess the agreement between different raters and/or different instruments. Often the same sample will be used to compare the agreement between two or more assessment methods for simplicity and to take advantage of the positive correlation of the ratings. Although sample size calculations have become an important element in the design of research projects, such methods for agreement studies are scarce. We adapt the generalized estimating equations approach for modelling dependent κ -statistics to estimate the sample size that is required for dependent agreement studies. We calculate the power based on a Wald test for the equality of two dependent κ -statistics. The Wald test statistic has a non-central χ ²-distribution with non-centrality parameter that can be estimated with minimal assumptions. The method proposed is useful for agreement studies with two raters and two instruments, and is easily extendable to multiple raters and multiple instruments. Furthermore, the method proposed allows for rater bias. Power calculations for binary ratings under various scenarios are presented. Analyses of two biomedical studies are used for illustration.     

Weighted composite quantile regression for partially linear varying coefficient models

Partially linear varying coefficient models (PLVCMs) with heteroscedasticity are considered in this article. Based on composite quantile regression, we develop a weighted composite quantile regression (WCQR) to estimate the non parametric varying coefficient functions and the parametric regression coefficients. The WCQR is augmented using a data-driven weighting scheme. Moreover, the asymptotic normality of proposed estimators for both the parametric and non parametric parts are studied explicitly. In addition, by comparing the asymptotic relative efficiency theoretically and numerically, WCQR method all outperforms the CQR method and some other estimate methods. To achieve sparsity with high-dimensional covariates, we develop a variable selection procedure to select significant parametric components for the PLVCM and prove the method possessing the oracle property. Both simulations and data analysis are conducted to illustrate the finite-sample performance of the proposed methods.     

Semiparametric Time-Varying Coefficients Regression Model for Longitudinal Data

Abstract.  In this paper, we consider a semiparametric time-varying coefficients regression model where the influences of some covariates vary non-parametrically with time while the effects of the remaining covariates follow certain parametric functions of time. The weighted least squares type estimators for the unknown parameters of the parametric coefficient functions as well as the estimators for the non-parametric coefficient functions are developed. We show that the kernel smoothing that avoids modelling of the sampling times is asymptotically more efficient than a single nearest neighbour smoothing that depends on the estimation of the sampling model. The asymptotic optimal bandwidth is also derived. A hypothesis testing procedure is proposed to test whether some covariate effects follow certain parametric forms. Simulation studies are conducted to compare the finite sample performances of the kernel neighbourhood smoothing and the single nearest neighbour smoothing and to check the empirical sizes and powers of the proposed testing procedures. An application to a data set from an AIDS clinical trial study is provided for illustration.     

State transition modeling of complex monitored health data

This article considers the analysis of complex monitored health data, where often one or several signals are reflecting the current health status that can be represented by a finite number of states, in addition to a set of covariates. In particular, we consider a novel application of a non-parametric state intensity regression method in order to study time-dependent effects of covariates on the state transition intensities. The method can handle baseline, time varying as well as dynamic covariates. Because of the non-parametric nature, the method can handle different data types and challenges under minimal assumptions. If the signal that is reflecting the current health status is of continuous nature, we propose the application of a weighted median and a hysteresis filter as data pre-processing steps in order to facilitate robust analysis. In intensity regression, covariates can be aggregated by a suitable functional form over a time history window. We propose to study the estimated cumulative regression parameters for different choices of the time history window in order to investigate short- and long-term effects of the given covariates. The proposed framework is discussed and applied to resuscitation data of newborns collected in Tanzania.     

Comparing the methods of measuring multi-rater agreement on an ordinal rating scale: a simulation study with an application to real data

Agreement among raters is an important issue in medicine, as well as in education and psychology. The agreement among two raters on a nominal or ordinal rating scale has been investigated in many articles. The multi-rater case with normally distributed ratings has also been explored at length. However, there is a lack of research on multiple raters using an ordinal rating scale. In this simulation study, several methods were compared with analyze rater agreement. The special case that was focused on was the multi-rater case using a bounded ordinal rating scale. The proposed methods for agreement were compared within different settings. Three main ordinal data simulation settings were used (normal, skewed and shifted data). In addition, the proposed methods were applied to a real data set from dermatology. The simulation results showed that the Kendall's W and mean gamma highly overestimated the agreement in data sets with shifts in data. ICC₄ for bounded data should be avoided in agreement studies with rating scales<5, where this method highly overestimated the simulated agreement. The difference in bias for all methods under study, except the mean gamma and Kendall's W, decreased as the rating scale increased. The bias of ICC₃ was consistent and small for nearly all simulation settings except the low agreement setting in the shifted data set. Researchers should be careful in selecting agreement methods, especially if shifts in ratings between raters exist and may apply more than one method before any conclusions are made.