A likelihood-based approach for multivariate one-sided tests with missing data

BackgroundMissing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.MethodsMethods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.ResultsType I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.ConclusionResults of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.

Summary We propose a method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. We use a multinomial model for the missing data indicators and propose a joint distribution for them which can be written as a sequence of one-dimensional conditional distributions, with each one-dimensional conditional distribution consisting of a logistic regression. We allow the covariates to be either categorical or continuous. The joint covariate distribution is also modelled via a sequence of one-dimensional conditional distributions, and the response variable is assumed to be completely observed. We derive the E- and M-steps of the EM algorithm with non-ignorable missing covariate data. For categorical covariates, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For continuous covariates, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. Computational techniques for Gibbs sampling are proposed and implemented. The parametric form of the assumed missing data mechanism itself is not ‘testable' from the data, and thus the non-ignorable modelling considered here can be viewed as a sensitivity analysis concerning a more complicated model. Therefore, although a model may have ‘passed' the tests for a certain missing data mechanism, this does not mean that we have captured, even approximately, the correct missing data mechanism. Hence, model checking for the missing data mechanism and sensitivity analyses play an important role in this problem and are discussed in detail. Several simulations are given to demonstrate the methodology. In addition, a real data set from a melanoma cancer clinical trial is presented to illustrate the methods proposed.

Asthma is an important chronic disease of childhood. An intervention programme for managing asthma was designed on principles of self-regulation and was evaluated by a randomized longitudinal study.The study focused on several outcomes, and, typically, missing data remained a pervasive problem. We develop a pattern-mixture model to evaluate the outcome of intervention on the number of hospitalizations with non-ignorable dropouts. Pattern-mixture models are not generally identifiable as no data may be available to estimate a number of model parameters. Sensitivity analyses are performed by imposing structures on the unidentified parameters.We propose a parameterization which permits sensitivity analyses on clustered longitudinal count data that have missing values due to non-ignorable missing data mechanisms. This parameterization is expressed as ratios between event rates across missing data patterns and the observed data pattern and thus measures departures from an ignorable missing data mechanism. Sensitivity analyses are performed within a Bayesian framework by averaging over different prior distributions on the event ratios. This model has the advantage of providing an intuitive and flexible framework for incorporating the uncertainty of the missing data mechanism in the final analysis.

BackgroundMissing data are a common problem in prospective studies with a long follow-up, and the volume, pattern and reasons for missing data may be relevant when estimating the cost of illness. We aimed to evaluate the effects of different methods for dealing with missing longitudinal cost data and for costing caregiver time on total societal costs in Alzheimer’s disease (AD).MethodsGERAS is an 18-month observational study of costs associated with AD. Total societal costs included patient health and social care costs, and caregiver health and informal care costs. Missing data were classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Simulation datasets were generated from baseline data with 10–40 % missing total cost data for each missing data mechanism. Datasets were also simulated to reflect the missing cost data pattern at 18 months using MAR and MNAR assumptions. Naïve and multiple imputation (MI) methods were applied to each dataset and results compared with complete GERAS 18-month cost data. Opportunity and replacement cost approaches were used for caregiver time, which was costed with and without supervision included and with time for working caregivers only being costed.ResultsTotal costs were available for 99.4 % of 1497 patients at baseline. For MCAR datasets, naïve methods performed as well as MI methods. For MAR, MI methods performed better than naïve methods. All imputation approaches were poor for MNAR data. For all approaches, percentage bias increased with missing data volume. For datasets reflecting 18-month patterns, a combination of imputation methods provided more accurate cost estimates (e.g. bias: −1 % vs −6 % for single MI method), although different approaches to costing caregiver time had a greater impact on estimated costs (29–43 % increase over base case estimate).ConclusionsMethods used to impute missing cost data in AD will impact on accuracy of cost estimates although varying approaches to costing informal caregiver time has the greatest impact on total costs. Tailoring imputation methods to the reason for missing data will further our understanding of the best analytical approach for studies involving cost outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-016-0188-1) contains supplementary material, which is available to authorized users.

Missing data in longitudinal studies , Missing data in longitudinal studies , کتابخانه دیجیتال جندی شاپور اهواز

Growth mixture models (GMMs) with nonignorable missing data have drawn increasing attention in research communities but have not been fully studied. The goal of this article is to propose and to evaluate a Bayesian method to estimate the GMMs with latent class dependent missing data. An extended GMM is first presented in which class probabilities depend on some observed explanatory variables and data missingness depends on both the explanatory variables and a latent class variable. A full Bayesian method is then proposed to estimate the model. Through the data augmentation method, conditional posterior distributions for all model parameters and missing data are obtained. A Gibbs sampling procedure is then used to generate Markov chains of model parameters for statistical inference. The application of the model and the method is first demonstrated through the analysis of mathematical ability growth data from the National Longitudinal Survey of Youth 1997 (Bureau of Labor Statistics, U.S. Department of Labor, 1997). A simulation study considering 3 main factors (the sample size, the class probability, and the missing data mechanism) is then conducted and the results show that the proposed Bayesian estimation approach performs very well under the studied conditions. Finally, some implications of this study, including the misspecified missingness mechanism, the sample size, the sensitivity of the model, the number of latent classes, the model comparison, and the future directions of the approach, are discussed.

We review the class of inverse probability weighting (IPW) approaches for the analysis of missing data under various missing data patterns and mechanisms. The IPW methods rely on the intuitive idea of creating a pseudo-population of weighted copies of the complete cases to remove selection bias introduced by the missing data. However, different weighting approaches are required depending on the missing data pattern and mechanism. We begin with a uniform missing data pattern (i.e. a scalar missing indicator indicating whether or not the full data is observed) to motivate the approach. We then generalise to more complex settings. Our goal is to provide a conceptual overview of existing IPW approaches and illustrate the connections and differences among these approaches.

FFQs are a popular method of capturing dietary information in epidemiological studies and may be used to derive dietary exposures such as nutrient intake or overall dietary patterns and diet quality. As FFQs can involve large numbers of questions, participants may fail to respond to all questions, leaving researchers to decide how to deal with missing data when deriving intake measures. The aim of the present commentary is to discuss the current practice for dealing with item non-response in FFQs and to propose a research agenda for reporting and handling missing data in FFQs. Single imputation techniques, such as zero imputation (assuming no consumption of the item) or mean imputation, are commonly used to deal with item non-response in FFQs. However, single imputation methods make strong assumptions about the missing data mechanism and do not reflect the uncertainty created by the missing data. This can lead to incorrect inference about associations between diet and health outcomes. Although the use of multiple imputation methods in epidemiology has increased, these have seldom been used in the field of nutritional epidemiology to address missing data in FFQs. We discuss methods for dealing with item non-response in FFQs, highlighting the assumptions made under each approach. Researchers analysing FFQs should ensure that missing data are handled appropriately and clearly report how missing data were treated in analyses. Simulation studies are required to enable systematic evaluation of the utility of various methods for handling item non-response in FFQs under different assumptions about the missing data mechanism.

Missing data are frequently encountered in longitudinal clinical trials. To better monitor and understand the progress over time, one must handle the missing data appropriately and examine whether the missing data mechanism is ignorable or nonignorable. In this article, we develop a new probit model for longitudinal binary response data. It resolves a challenging issue for estimating the variance of the random effects, and substantially improves the convergence and mixing of the Gibbs sampling algorithm. We show that when improper uniform priors are specified for the regression coefficients of the joint multinomial model via a sequence of one-dimensional conditional distributions for the missing data indicators under nonignorable missingness, the joint posterior distribution is improper. A variation of Jeffreys prior is thus established as a remedy for the improper posterior distribution. In addition, an efficient Gibbs sampling algorithm is developed using a collapsing technique. Two model assessment criteria, the deviance information criterion (DIC) and the logarithm of the pseudomarginal likelihood (LPML), are used to guide the choices of prior specifications and to compare the models under different missing data mechanisms. We report on extensive simulations conducted to investigate the empirical performance of the proposed methods. The proposed methodology is further illustrated using data from an HIV prevention clinical trial.

The true missing data mechanism is never known in practice. We present a method for generating multiple imputations for binary variables, which formally incorporates missing data mechanism uncertainty. Imputations are generated from a distribution of imputation models rather than a single model, with the distribution reflecting subjective notions of missing data mechanism uncertainty. Parameter estimates and standard errors are obtained using rules for nested multiple imputation. Using simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal smoking cessation trial where nonignorably missing data were a concern. Our method provides a simple approach for formalizing subjective notions regarding nonresponse and can be implemented using existing imputation software.

Social network data often contain missing values because of the sensitive nature of the information collected and the dependency among the network actors. As a response, network imputation methods including simple ones constructed from network structural characteristics and more complicated model-based ones have been developed. Although past studies have explored the influence of missing data on social networks and the effectiveness of imputation procedures in many missing data conditions, the current study aims to evaluate a more extensive set of eight network imputation techniques (i.e., null-tie, Reconstruction, Preferential Attachment, Constrained Random Dot Product Graph, Multiple Imputation by Bayesian Exponential Random Graph Models or BERGMs, k-Nearest Neighbors, Random Forest, and Multiple Imputation by Chained Equations) under more practical conditions through comprehensive simulation. A factorial design for missing data conditions is adopted with factors including missing data types, missing data mechanisms, and missing data proportions, which are applied to generated social networks with varying numbers of actors based on 4 different sets of coefficients in ERGMs. Results show that the effectiveness of imputation methods differs by missing data types, missing data mechanisms, the evaluation criteria used, and the complexity of the social networks. More complex methods such as the BERGMs have consistently good performances in recovering missing edges that should have been present. While simpler methods like Reconstruction work better in recovering network statistics when the missing proportion of present edges is low, the BERGMs work better when more present edges are missing. The BERGMs also work well in recovering ERGM coefficients when the networks are complex and the missing data type is actor non-response. In conclusion, researchers analyzing social networks with incomplete data should identify the network structures of interest and the potential missing data types before selecting appropriate imputation methods.

Background Missing data is common in IBD trials. Depending on the volume and nature of missing data, it can reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients (patients) with missing data are considered treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in IBD trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid (HI) approach combining NRI and multiple imputation (MI) as an alternative to NRI in the analyses of two phase 3 trials of vedolizumab (VDZ) in patients with moderate-to-severe UC – VISIBLE 11 and VARSITY2. Methods VISIBLE 1 and VARSITY assessed efficacy using dichotomous endpoints based on complete Mayo score. Full methodologies reported previously.1,2 Our proposed HI approach is aimed at imputing missing Mayo scores, instead of imputing the missing dichotomous efficacy endpoint. To assess the impact of dropouts for different missing data mechanisms (categorised as ‘missing not at random [MNAR]’ and ‘missing at random [MAR]’, HI was implemented as a potential sensitivity analysis, where dropouts owing to safety or lack of efficacy were imputed using NRI (assuming MNAR) and other missing data were imputed using MI (assuming MAR). For MI, each component of the Mayo score was imputed via a multivariate stepwise approach using a fully conditional specification ordinal logistic method. Missing baseline scores were imputed using baseline characteristics data. Missing scores from each subsequent visit were imputed using all previous visits in a stepwise fashion. Fifty imputation datasets were computed for each component of Mayo score. The complete Mayo score and relevant efficacy endpoints were derived subsequently. The analysis was performed within each imputed dataset to determine treatment difference, 95% CI and p-value, which were then combined via Rubin’s rules3. Results Tables 1 and 2 show a comparison of efficacy in the two studies using the primary NRI analysis vs. the alternative HI approach for handling missing data. Conclusion HI and NRI approaches can provide consistent efficacy analyses in IBD trials. The HI approach can serve as a useful sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions. Reference

Traditional data envelopment analysis (DEA) is used under the premise that inputs and outputs are exact values. If it is not true, the DEA approach is unavailable. However, it is common that some of the entries in the data are missing in practice. As a result, the current paper performs efficiency evaluation with missing data considering the missing-data properties (missing-data patterns and missing-data mechanisms). A multiple imputation (MI) approach is used to estimate the missing values. The MI approach is applied to a forest reorganisation problem for reliability. An example of public secondary schools is given to illustrate the proposed technique. When input or output values for decision making units (DMUs) continuously vary under an interval, the current paper characterises a DMU’s pessimistic and optimistic efficiency functions of an input or output of most interest. A Monte Carlo simulation technique is used to obtain a DMU’s efficiency distribution.

Longitudinal data analysis had been widely developed in the past three decades. Longitudinal data are common in many fields such as public health, medicine, biological and social sciences. Longitudinal data have special nature as the individual may be observed during a long period of time. Hence, missing values are common in longitudinal data. The presence of missing values leads to biased results and complicates the analysis. The missing values have two patterns: intermittent and dropout. The missing data mechanisms are missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). The appropriate analysis relies heavily on the assumed mechanism and pattern. The parametric fractional imputation is developed to handle longitudinal data with intermittent missing pattern. The maximum likelihood estimates are obtained and the Jackkife method is used to obtain the standard errors of the parameters estimates. Finally a simulation study is conducted to validate the proposed approach. Also, the proposed approach is applied to a real data.

The impact of the missing data mechanism on estimates of model parameters for continuous data has been extensively investigated in the literature. In comparison, minimal research has been carried out for the impact of missing count data. The focus of this article is to investigate the impact of missing data on a transition model, termed the generalized autoregressive model of order 1 for longitudinal count data. The model has several features, including modeling dependence and accounting for overdispersion in the data, that make it appealing for the clinical trial setting. Furthermore, the model can be viewed as a natural extension of the commonly used log-linear model. Following introduction of the model and discussion of its estimation we investigate the impact of different missing data mechanisms on estimates of the model parameters through a simulation experiment. The findings of the simulation experiment show that, as in the case of normally distributed data, estimates under the missing completely at random (MCAR) and missing at random (MAR) mechanisms are close to their analogue for the full dataset and that the missing not at random (MNAR) mechanism has the greatest bias. Furthermore, estimates based on imputing the last observed value carried forward (LOCF) for missing data under the MAR assumption are similar to those of the MAR. This latter finding might be attributed to the Markov property underlying the model and to the high level of dependence among successive observations used in the simulation experiment. Finally, we consider an application of the generalized autoregressive model to a longitudinal epilepsy dataset analyzed in the literature.