Causal inference for recurrent events data with all-or-none compliance

ABSTRACT

In this article, causal inference in randomized studies with recurrent events data and all-or-none compliance is considered. We use the counting process to analyze the recurrent events data and propose a causal proportional intensity model. The maximum likelihood approach is adopted to estimate the parameters of the proposed causal model. To overcome the computational difficulties created by the mixture structure of the problem, we develop an expectation-maximization (EM) algorithm. The resulting estimators are shown to be consistent and asymptotically normal. We further estimate the complier average causal effect (CACE), which is defined as the difference of the average numbers of recurrence between treatment and control groups within the complier class. The corresponding inferential procedures are established. Some simulation studies are conducted to assess the finite sample performance of the proposed approach.     

Semiparametric regression for the mean and rate functions of recurrent events

The counting process with the Cox-type intensity function has been commonly used to analyse recurrent event data. This model essentially assumes that the underlying counting process is a time-transformed Poisson process and that the covariates have multiplicative effects on the mean and rate function of the counting process. Recently, Pepe and Cai, and Lawless and co-workers have proposed semiparametric procedures for making inferences about the mean and rate function of the counting process without the Poisson-type assumption. In this paper, we provide a rigorous justification of such robust procedures through modern empirical process theory. Furthermore, we present an approach to constructing simultaneous confidence bands for the mean function and describe a class of graphical and numerical techniques for checking the adequacy of the fitted mean–rate model. The advantages of the robust procedures are demonstrated through simulation studies. An illustration with multiple-infection data taken from a clinical study on chronic granulomatous disease is also provided.     

Semiparametric models: a generalized self-consistency approach

Summary. In semiparametric models, the dimension d of the maximum likelihood problem is potentially unlimited. Conventional estimation methods generally behave like O ( d ³). A new O ( d ) estimation procedure is proposed for a large class of semiparametric models. Potentially unlimited dimension is handled in a numerically efficient way through a Nelson–Aalen-like estimator. Discussion of the new method is put in the context of recently developed minorization–maximization algorithms based on surrogate objective functions. The procedure for semiparametric models is used to demonstrate three methods to construct a surrogate objective function: using the difference of two concave functions, the EM way and the new quasi-EM (QEM) approach. The QEM approach is based on a generalization of the EM-like construction of the surrogate objective function so it does not depend on the missing data representation of the model. Like the EM algorithm, the QEM method has a dual interpretation, a result of merging the idea of surrogate maximization with the idea of imputation and self-consistency. The new approach is compared with other possible approaches by using simulations and analysis of real data. The proportional odds model is used as an example throughout the paper.     

Pseudo-full likelihood estimation for prospective survival analysis with a general semiparametric shared frailty model: Asymptotic theory

In this work we present a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Earlier work showed this method to perform well in a simulation study. Here we provide rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter, including consistent variance estimators.     

A class of accelerated means regression models for recurrent event data

In this article, we propose a general class of accelerated means regression models for recurrent event data. The class includes the proportional means model, the accelerated failure time model and the accelerated rates model as special cases. The new model offers great flexibility in formulating the effects of covariates on the mean functions of counting processes while leaving the stochastic structure completely unspecified. For the inference on the model parameters, estimating equation approaches are developed and both large and final sample properties of the proposed estimators are established. In addition, some graphical and numerical procedures are presented for model checking. An illustration with multiple-infection data from a clinic study on chronic granulomatous disease is also provided.     

Asymptotics for a class of dynamic recurrent event models

Asymptotic properties, both consistency and weak convergence, of estimators arising in a general class of dynamic recurrent event models are presented. The class of models take into account the impact of interventions after each event occurrence, the impact of accumulating event occurrences, the induced informative and dependent right-censoring mechanism due to the data-accrual scheme, and the effect of covariate processes on the recurrent event occurrences. The class of models subsumes as special cases many of the recurrent event models that have been considered in biostatistics, reliability, and in the social sciences. The asymptotic properties presented have the potential of being useful in developing goodness-of-fit and model validation procedures, confidence intervals and confidence bands constructions, and hypothesis testing procedures for the finite- and infinite-dimensional parameters of a general class of dynamic recurrent event models, albeit the models without frailties.     

Semiparametric inference for the recurrent events process by means of a single-index model

In this paper, we introduce new parametric and semiparametric regression techniques for a recurrent event process subject to random right censoring. We develop models for the cumulative mean function and provide asymptotically normal estimators. Our semiparametric model which relies on a single-index assumption can be seen as a dimension reduction technique that, contrary to a fully nonparametric approach, is not stroke by the curse of dimensionality when the number of covariates is high. We discuss data-driven techniques to choose the parameters involved in the estimation procedures and provide a simulation study to support our theoretical results.     

A class of partially linear transformation models for recurrent gap times

In this article, we propose a general class of partially linear transformation models for recurrent gap time data, which extends the linear transformation models by incorporating non linear covariate effects and includes the partially linear proportional hazards and the partially linear proportional odds models as special cases. Both global and local estimating equations are developed to estimate the parametric and non parametric covariate effects, and the asymptotic properties of the resulting estimators are established. The finite-sample behavior of the proposed estimators is evaluated through simulation studies, and an application to a clinic study on chronic granulomatous disease is provided.     

A class of linear transformation models for interval censored data with a cured proportion

Interval-censored data arise due to a sequence random examination such that the failure time of interest occurs in an interval. In some medical studies, there exist long-term survivors who can be considered as permanently cured. We consider a mixed model for the uncured group coming from linear transformation models and cured group coming from a logistic regression model. For the inference of parameters, an EM algorithm is developed for a full likelihood approach. To investigate finite sample properties of the proposed method, simulation studies are conducted. The approach is applied to the National Aeronautics and Space Administration’s hypobaric decompression sickness data.     

A new test for residual randomness in a class of dynamic autocorrelated econometric models

This paper presents a new test statistic for dynamic or stochastic mis-specification for the dynamic demand or dynamic adjustment class of economic models. The test statistic is based on residual autocorrelations, asymptotically X² and is suspected to be of low power. The test is illustrated with an example from recent econometric literature.     

A class of mixed models for recurrent event data

In this article, we propose a class of mixed models for recurrent event data. The new models include the proportional rates model and Box–Cox transformation rates models as special cases, and allow the effects of covariates on the rate functions of counting processes to be proportional or convergent. For inference on the model parameters, estimating equation approaches are developed. The asymptotic properties of the resulting estimators are established and the finite sample performance of the proposed procedure is evaluated through simulation studies. A real example with data taken from a clinic study on chronic granulomatous disease (CGD) is also illustrated for the use of the proposed methodology. The Canadian Journal of Statistics 39: 578–590; 2011. © 2011 Statistical Society of Canada     

Review and implementation of cure models based on first hitting times for Wiener processes

The development of models and methods for cure rate estimation has recently burgeoned into an important subfield of survival analysis. Much of the literature focuses on the standard mixture model. Recently, process-based models have been suggested. We focus on several models based on first passage times for Wiener processes. Whitmore and others have studied these models in a variety of contexts. Lee and Whitmore (Stat Sci 21(4):501–513, 2006) give a comprehensive review of a variety of first hitting time models and briefly discuss their potential as cure rate models. In this paper, we study the Wiener process with negative drift as a possible cure rate model but the resulting defective inverse Gaussian model is found to provide a poor fit in some cases. Several possible modifications are then suggested, which improve the defective inverse Gaussian. These modifications include: the inverse Gaussian cure rate mixture model; a mixture of two inverse Gaussian models; incorporation of heterogeneity in the drift parameter; and the addition of a second absorbing barrier to the Wiener process, representing an immunity threshold. This class of process-based models is a useful alternative to the standard model and provides an improved fit compared to the standard model when applied to many of the datasets that we have studied. Implementation of this class of models is facilitated using expectation-maximization (EM) algorithms and variants thereof, including the gradient EM algorithm. Parameter estimates for each of these EM algorithms are given and the proposed models are applied to both real and simulated data, where they perform well.     

On selecting a prior for the precision parameter of Dirichlet process mixture models

In hierarchical mixture models the Dirichlet process is used to specify latent patterns of heterogeneity, particularly when the distribution of latent parameters is thought to be clustered (multimodal). The parameters of a Dirichlet process include a precision parameter α$\alpha$ and a base probability measure _G0$G_0$. In problems where α$\alpha$ is unknown and must be estimated, inferences about the level of clustering can be sensitive to the choice of prior assumed for α$\alpha$. In this paper an approach is developed for computing a prior for the precision parameter α$\alpha$ that can be used in the presence or absence of prior information about the level of clustering. This approach is illustrated in an analysis of counts of stream fishes. The results of this fully Bayesian analysis are compared with an empirical Bayes analysis of the same data and with a Bayesian analysis based on an alternative commonly used prior.