Empirical likelihood for linear regression models under imputation for missing responses

The authors study the empirical likelihood method for linear regression models. They show that when missing responses are imputed using least squares predictors, the empirical log‐likelihood ratio is asymptotically a weighted sum of chi‐square variables with unknown weights. They obtain an adjusted empirical log‐likelihood ratio which is asymptotically standard chi‐square and hence can be used to construct confidence regions. They also obtain a bootstrap empirical log‐likelihood ratio and use its distribution to approximate that of the empirical log‐likelihood ratio. A simulation study indicates that the proposed methods are comparable in terms of coverage probabilities and average lengths of confidence intervals, and perform better than a normal approximation based method.     

Empirical likelihood confidence intervals under imputation for missing survey data from stratified simple random sampling

Missing observations due to non‐response are commonly encountered in data collected from sample surveys. The focus of this article is on item non‐response which is often handled by filling in (or imputing) missing values using the observed responses (donors). Random imputation (single or fractional) is used within homogeneous imputation classes that are formed on the basis of categorical auxiliary variables observed on all the sampled units. A uniform response rate within classes is assumed, but that rate is allowed to vary across classes. We construct confidence intervals (CIs) for a population parameter that is defined as the solution to a smooth estimating equation with data collected using stratified simple random sampling. The imputation classes are assumed to be formed across strata. Fractional imputation with a fixed number of random draws is used to obtain an imputed estimating function. An empirical likelihood inference method under the fractional imputation is proposed and its asymptotic properties are derived. Two asymptotically correct bootstrap methods are developed for constructing the desired CIs. In a simulation study, the proposed bootstrap methods are shown to outperform traditional bootstrap methods and some non‐bootstrap competitors under various simulation settings. The Canadian Journal of Statistics 47: 281–301; 2019 © 2019 Statistical Society of Canada     

Latent class based multiple imputation approach for missing categorical data

In this paper we propose a latent class based multiple imputation approach for analyzing missing categorical covariate data in a highly stratified data model. In this approach, we impute the missing data assuming a latent class imputation model and we use likelihood methods to analyze the imputed data. Via extensive simulations, we study its statistical properties and make comparisons with complete case analysis, multiple imputation, saturated log-linear multiple imputation and the Expectation–Maximization approach under seven missing data mechanisms (including missing completely at random, missing at random and not missing at random). These methods are compared with respect to bias, asymptotic standard error, type I error, and 95% coverage probabilities of parameter estimates. Simulations show that, under many missingness scenarios, latent class multiple imputation performs favorably when jointly considering these criteria. A data example from a matched case–control study of the association between multiple myeloma and polymorphisms of the Inter-Leukin 6 genes is considered.     

Empirical Likelihood Inference for the Rao‐Hartley‐Cochran Sampling Design

The Hartley‐Rao‐Cochran sampling design is an unequal probability sampling design which can be used to select samples from finite populations. We propose to adjust the empirical likelihood approach for the Hartley‐Rao‐Cochran sampling design. The approach proposed intrinsically incorporates sampling weights, auxiliary information and allows for large sampling fractions. It can be used to construct confidence intervals. In a simulation study, we show that the coverage may be better for the empirical likelihood confidence interval than for standard confidence intervals based on variance estimates. The approach proposed is simple to implement and less computer intensive than bootstrap. The confidence interval proposed does not rely on re‐sampling, linearization, variance estimation, design‐effects or joint inclusion probabilities.     

Multiple imputation methods for recurrent event data with missing event category

Frequently in clinical and epidemiologic studies, the event of interest is recurrent (i.e., can occur more than once per subject). When the events are not of the same type, an analysis which accounts for the fact that events fall into different categories will often be more informative. Often, however, although event times may always be known, information through which events are categorized may potentially be missing. Complete‐case methods (whose application may require, for example, that events be censored when their category cannot be determined) are valid only when event categories are missing completely at random. This assumption is rather restrictive. The authors propose two multiple imputation methods for analyzing multiple‐category recurrent event data under the proportional means/rates model. The use of a proper or improper imputation technique distinguishes the two approaches. Both methods lead to consistent estimation of regression parameters even when the missingness of event categories depends on covariates. The authors derive the asymptotic properties of the estimators and examine their behaviour in finite samples through simulation. They illustrate their approach using data from an international study on dialysis.     

Multiple imputation for ordinal longitudinal data with monotone missing data patterns

Missing data often complicate the analysis of scientific data. Multiple imputation is a general purpose technique for analysis of datasets with missing values. The approach is applicable to a variety of missing data patterns but often complicated by some restrictions like the type of variables to be imputed and the mechanism underlying the missing data. In this paper, the authors compare the performance of two multiple imputation methods, namely fully conditional specification and multivariate normal imputation in the presence of ordinal outcomes with monotone missing data patterns. Through a simulation study and an empirical example, the authors show that the two methods are indeed comparable meaning any of the two may be used when faced with scenarios, at least, as the ones presented here.     

Doubly Robust Inference for the Distribution Function in the Presence of Missing Survey Data

Item non‐response in surveys occurs when some, but not all, variables are missing. Unadjusted estimators tend to exhibit some bias, called the non‐response bias, if the respondents differ from the non‐respondents with respect to the study variables. In this paper, we focus on item non‐response, which is usually treated by some form of single imputation. We examine the properties of doubly robust imputation procedures, which are those that lead to an estimator that remains consistent if either the outcome variable or the non‐response mechanism is adequately modelled. We establish the double robustness property of the imputed estimator of the finite population distribution function under random hot‐deck imputation within classes. We also discuss the links between our approach and that of Chambers and Dunstan. The results of a simulation study support our findings.     

Doubly robust point and variance estimation in the presence of imputed survey data

Imputation is often used in surveys to treat item nonresponse. It is well known that treating the imputed values as observed values may lead to substantial underestimation of the variance of the point estimators. To overcome the problem, a number of variance estimation methods have been proposed in the literature, including resampling methods such as the jackknife and the bootstrap. In this paper, we consider the problem of doubly robust inference in the presence of imputed survey data. In the doubly robust literature, point estimation has been the main focus. In this paper, using the reverse framework for variance estimation, we derive doubly robust linearization variance estimators in the case of deterministic and random regression imputation within imputation classes. Also, we study the properties of several jackknife variance estimators under both negligible and nonnegligible sampling fractions. A limited simulation study investigates the performance of various variance estimators in terms of relative bias and relative stability. Finally, the asymptotic normality of imputed estimators is established for stratified multistage designs under both deterministic and random regression imputation. The Canadian Journal of Statistics 40: 259–281; 2012 © 2012 Statistical Society of Canada     

Control‐based imputation for sensitivity analyses in informative censoring for recurrent event data

In clinical trials, missing data commonly arise through nonadherence to the randomized treatment or to study procedure. For trials in which recurrent event endpoints are of interests, conventional analyses using the proportional intensity model or the count model assume that the data are missing at random, which cannot be tested using the observed data alone. Thus, sensitivity analyses are recommended. We implement the control‐based multiple imputation as sensitivity analyses for the recurrent event data. We model the recurrent event using a piecewise exponential proportional intensity model with frailty and sample the parameters from the posterior distribution. We impute the number of events after dropped out and correct the variance estimation using a bootstrap procedure. We apply the method to an application of sitagliptin study.     

Statistical inference under imputation for proportional hazard model with missing covariates

Missing covariate data are common in biomedical studies. In this article, by using the non parametric kernel regression technique, a new imputation approach is developed for the Cox-proportional hazard regression model with missing covariates. This method achieves the same efficiency as the fully augmented weighted estimators (Qi et al. 2005. Journal of the American Statistical Association, 100:1250) and has a simpler form. The asymptotic properties of the proposed estimator are derived and analyzed. The comparisons between the proposed imputation method and several other existing methods are conducted via a number of simulation studies and a mouse leukemia data.     

Inference on Polychotomous Responses in Finite Populations

Abstract. A model‐based predictive estimator is proposed for the population proportions of a polychotomous response variable, based on a sample from the population and on auxiliary variables, whose values are known for the entire population. The responses for the non‐sample units are predicted using a multinomial logit model, which is a parametric function of the auxiliary variables. A bootstrap estimator is proposed for the variance of the predictive estimator, its consistency is proved and its small sample performance is compared with that of an analytical estimator. The proposed predictive estimator is compared with other available estimators, including model‐assisted ones, both in a simulation study involving different sampling designs and model mis‐specification, and using real data from an opinion survey. The results indicate that the prediction approach appears to use auxiliary information more efficiently than the model‐assisted approach.     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.     

Review of guidelines and literature for handling missing data in longitudinal clinical trials with a case study

Missing data in clinical trials are inevitable. We highlight the ICH guidelines and CPMP points to consider on missing data. Specifically, we outline how we should consider missing data issues when designing, planning and conducting studies to minimize missing data impact. We also go beyond the coverage of the above two documents, provide a more detailed review of the basic concepts of missing data and frequently used terminologies, and examples of the typical missing data mechanism, and discuss technical details and literature for several frequently used statistical methods and associated software. Finally, we provide a case study where the principles outlined in this paper are applied to one clinical program at protocol design, data analysis plan and other stages of a clinical trial.     

Calibration approach for estimating population total with subsampling of non respondents under single- and two-phase sampling

ABSTRACT

Using the calibration approach, the Hansen and Hurwitz (1946 Hansen, M.H., Hurwitz, W.N. (1946). The problem of non response in sample surveys. J. Am. Stat. Assoc. 46:147–190.[Taylor & Francis Online] , [Google Scholar]) technique-based estimator is developed for the situation where the information on auxiliary variable is assumed known for the entire population units. The double-sampling case has also been dealt with. Expressions for the estimator of population total, its variance, and variance estimator are developed. The theoretical results are illustrated with the help of simulation studies. Simulation results show that the proposed calibration approach-based estimator outperforms the Hansen and Hurwitz estimator.     

Inference for longitudinal data from complex sampling surveys: An approach based on quadratic inference functions

We propose a survey weighted quadratic inference function method for the analysis of data collected from longitudinal surveys, as an alternative to the survey weighted generalized estimating equation method. The procedure yields estimators of model parameters, which are shown to be consistent and have a limiting normal distribution. Furthermore, based on the inference function, a pseudolikelihood ratio type statistic for testing a composite hypothesis on model parameters and a statistic for testing the goodness of fit of the assumed model are proposed. We establish their asymptotic distributions as weighted sums of independent chi‐squared random variables and obtain Rao‐Scott corrections to those statistics leading to a chi‐squared distribution, approximately. We examine the performance of the proposed methods in a simulation study.     

Inference in Semi‐Parametric Dynamic Models for Repeated Count Data

This paper deals with a longitudinal semi‐parametric regression model in a generalised linear model setup for repeated count data collected from a large number of independent individuals. To accommodate the longitudinal correlations, we consider a dynamic model for repeated counts which has decaying auto‐correlations as the time lag increases between the repeated responses. The semi‐parametric regression function involved in the model contains a specified regression function in some suitable time‐dependent covariates and a non‐parametric function in some other time‐dependent covariates. As far as the inference is concerned, because the non‐parametric function is of secondary interest, we estimate this function consistently using the independence assumption‐based well‐known quasi‐likelihood approach. Next, the proposed longitudinal correlation structure and the estimate of the non‐parametric function are used to develop a semi‐parametric generalised quasi‐likelihood approach for consistent and efficient estimation of the regression effects in the parametric regression function. The finite sample performance of the proposed estimation approach is examined through an intensive simulation study based on both large and small samples. Both balanced and unbalanced cluster sizes are incorporated in the simulation study. The asymptotic performances of the estimators are given. The estimation methodology is illustrated by reanalysing the well‐known health care utilisation data consisting of counts of yearly visits to a physician by 180 individuals for four years and several important primary and secondary covariates.     

A copula‐graphic estimator for the conditional survival function under dependent censoring

Rivest Wells (2001) showed that in situations where the dependence between a lifetime and a censoring variable can be modeled by a given Archimedean copula, the copula‐graphic estimator of Zheng Klein (1995) has an explicit form. The authors extend this work to the fixed design regression case. They show that the copula‐graphic estimator then has an asymptotic representation and a Gaussian limit. They also assess the influence of a misspecified copula function on the performance of the estimator. Their developments are illustrated with data on the survival of the Atlantic halibut.     

Characterization of dose‐response for count data using a generalized MCP‐Mod approach in an adaptive dose‐ranging trial

Understanding the dose–response relationship is a key objective in Phase II clinical development. Yet, designing a dose‐ranging trial is a challenging task, as it requires identifying the therapeutic window and the shape of the dose–response curve for a new drug on the basis of a limited number of doses. Adaptive designs have been proposed as a solution to improve both quality and efficiency of Phase II trials as they give the possibility to select the dose to be tested as the trial goes. In this article, we present a ‘shapebased’ two‐stage adaptive trial design where the doses to be tested in the second stage are determined based on the correlation observed between efficacy of the doses tested in the first stage and a set of pre‐specified candidate dose–response profiles. At the end of the trial, the data are analyzed using the generalized MCP‐Mod approach in order to account for model uncertainty. A simulation study shows that this approach gives more precise estimates of a desired target dose (e.g. ED70) than a single‐stage (fixed‐dose) design and performs as well as a two‐stage D‐optimal design. We present the results of an adaptive model‐based dose‐ranging trial in multiple sclerosis that motivated this research and was conducted using the presented methodology. Copyright © 2015 John Wiley & Sons, Ltd.