Estimating the causal effects in randomized trials for survival data with a cure fraction and non compliance

We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.     

Nonparametric analysis of recurrent gap time data

Abstract

Recurrent event data are frequently encountered in longitudinal studies. In many applications, the times between successive recurrent events (gap times) are often of interest and lead to problems that have received much attention recently. In this article, using the approach of inverse probability-of-censoring weights (IPCW), we propose nonparametric estimators for the estimation of the bivariate distribution and survival functions for gap times of recurrent event data. We also consider the estimation of Kendall’s tau for two gap times by expressing it as an integral functional of the bivariate survival function. The asymptotic properties of the proposed estimators are established. Simulation studies are conducted to investigate their finite sample performance.     

Matching Using Sufficient Dimension Reduction for Causal Inference

ABSTRACT

To estimate causal treatment effects, we propose a new matching approach based on the reduced covariates obtained from sufficient dimension reduction. Compared with the original covariates and the propensity score, which are commonly used for matching in the literature, the reduced covariates are nonparametrically estimable and are effective in imputing the missing potential outcomes, under a mild assumption on the low-dimensional structure of the data. Under the ignorability assumption, the consistency of the proposed approach requires a weaker common support condition. In addition, researchers are allowed to employ different reduced covariates to find matched subjects for different treatment groups. We develop relevant asymptotic results and conduct simulation studies as well as real data analysis to illustrate the usefulness of the proposed approach.     

Analyzing panel count data with a dependent observation process and a terminal event

Panel count data occur in many fields and a number of approaches have been developed. However, most of these approaches are for situations where there is no terminal event and the observation process is independent of the underlying recurrent event process unconditionally or conditional on the covariates. In this paper, we discuss a more general situation where the observation process is informative and there exists a terminal event which precludes further occurrence of the recurrent events of interest. For the analysis, a semiparametric transformation model is presented for the mean function of the underlying recurrent event process among survivors. To estimate the regression parameters, an estimating equation approach is proposed in which an inverse survival probability weighting technique is used. The asymptotic distribution of the proposed estimates is provided. Simulation studies are conducted and suggest that the proposed approach works well for practical situations. An illustrative example is provided. The Canadian Journal of Statistics 41: 174–191; 2013 © 2012 Statistical Society of Canada     

Model averaging by jackknife criterion for varying-coefficient partially linear models

Abstract

This paper is concerned with model averaging procedure for varying-coefficient partially linear models. We proposed a jackknife model averaging method that involves minimizing a leave-one-out cross-validation criterion, and developed a computational shortcut to optimize the cross-validation criterion for weight choice. The resulting model average estimator is shown to be asymptotically optimal in terms of achieving the smallest possible squared error. The simulation studies have provided evidence of the superiority of the proposed procedures. Our approach is further applied to a real data.     

Estimating Causal Effects in Trials Involving Multi-Treatment Arms Subject to Non-compliance: A Bayesian framework

Data analysis for randomized trials including multi-treatment arms is often complicated by subjects who do not comply with their treatment assignment. We discuss here methods of estimating treatment efficacy for randomized trials involving multi-treatment arms subject to non-compliance. One treatment effect of interest in the presence of non-compliance is the complier average causal effect (CACE) (Angrist et al. 1996), which is defined as the treatment effect for subjects who would comply regardless of the assigned treatment. Following the idea of principal stratification (Frangakis & Rubin 2002), we define principal compliance (Little et al. 2009) in trials with three treatment arms, extend CACE and define causal estimands of interest in this setting. In addition, we discuss structural assumptions needed for estimation of causal effects and the identifiability problem inherent in this setting from both a Bayesian and a classical statistical perspective. We propose a likelihood-based framework that models potential outcomes in this setting and a Bayes procedure for statistical inference. We compare our method with a method of moments approach proposed by Cheng & Small (2006) using a hypothetical data set, and further illustrate our approach with an application to a behavioral intervention study (Janevic et al. 2003).     

Estimating finite mixture of continuous trees using penalized mutual information

Abstract

In this paper we introduce continuous tree mixture model that is the mixture of undirected graphical models with tree structured graphs and is considered as multivariate analysis with a non parametric approach. We estimate its parameters, the component edge sets and mixture proportions through regularized maximum likalihood procedure. Our new algorithm, which uses expectation maximization algorithm and the modified version of Kruskal algorithm, simultaneosly estimates and prunes the mixture component trees. Simulation studies indicate this method performs better than the alternative Gaussian graphical mixture model. The proposed method is also applied to water-level data set and is compared with the results of Gaussian mixture model.     

A joint modelling approach for clustered recurrent events and death events

In dental implant research studies, events such as implant complications including pain or infection may be observed recurrently before failure events, i.e. the death of implants. It is natural to assume that recurrent events and failure events are correlated to each other, since they happen on the same implant (subject) and complication times have strong effects on the implant survival time. On the other hand, each patient may have more than one implant. Therefore these recurrent events or failure events are clustered since implant complication times or failure times within the same patient (cluster) are likely to be correlated. The overall implant survival times and recurrent complication times are both interesting to us. In this paper, a joint modelling approach is proposed for modelling complication events and dental implant survival times simultaneously. The proposed method uses a frailty process to model the correlation within cluster and the correlation within subjects. We use Bayesian methods to obtain estimates of the parameters. Performance of the joint models are shown via simulation studies and data analysis.     

Semiparametric proportional means model for marker data contingent on recurrent event

In many biomedical studies with recurrent events, some markers can only be measured when events happen. For example, medical cost attributed to hospitalization can only incur when patients are hospitalized. Such marker data are contingent on recurrent events. In this paper, we present a proportional means model for modelling the markers using the observed covariates contingent on the recurrent event. We also model the recurrent event via a marginal rate model. Estimating equations are constructed to derive the point estimators for the parameters in the proposed models. The estimators are shown to be asymptotically normal. Simulation studies are conducted to examine the finite-sample properties of the proposed estimators and the proposed method is applied to a data set from the Vitamin A Community Trial.     

A hybrid method to estimate the full parametric hazard model

Abstract

In this paper, we propose a hybrid method to estimate the baseline hazard for Cox proportional hazard model. In the proposed method, the nonparametric estimate of the survival function by Kaplan Meier, and the parametric estimate of the logistic function in the Cox proportional hazard by partial likelihood method are combined to estimate a parametric baseline hazard function. We compare the estimated baseline hazard using the proposed method and the Cox model. The results show that the estimated baseline hazard using hybrid method is improved in comparison with estimated baseline hazard using the Cox model. The performance of each method is measured based on the estimated parameters of the baseline distribution as well as goodness of fit of the model. We have used real data as well as simulation studies to compare performance of both methods. Monte Carlo simulations carried out in order to evaluate the performance of the proposed method. The results show that the proposed hybrid method provided better estimate of the baseline in comparison with the estimated values by the Cox model.     

A functional coefficient GARCH-M model

ABSTRACT

Motivated by the time varying property of the risk aversion and the functional coefficient regression model, a functional coefficient GARCH-M model is studied. The proposed GARCH-M type model gives a way to study the relationship between risk aversion and certain variable. An approach is given to estimate the model and some theoretical results are obtained. Simulations demonstrate that the method performs well. From the empirical studies, it is shown that the proposed model can better fit the considered data compared to the usual parametric models.     

Additive–multiplicative rates model for recurrent events

Recurrent events are frequently encountered in biomedical studies. Evaluating the covariates effects on the marginal recurrent event rate is of practical interest. There are mainly two types of rate models for the recurrent event data: the multiplicative rates model and the additive rates model. We consider a more flexible additive–multiplicative rates model for analysis of recurrent event data, wherein some covariate effects are additive while others are multiplicative. We formulate estimating equations for estimating the regression parameters. The estimators for these regression parameters are shown to be consistent and asymptotically normally distributed under appropriate regularity conditions. Moreover, the estimator of the baseline mean function is proposed and its large sample properties are investigated. We also conduct simulation studies to evaluate the finite sample behavior of the proposed estimators. A medical study of patients with cystic fibrosis suffered from recurrent pulmonary exacerbations is provided for illustration of the proposed method.     

Reducing sample size needed for cox-proportional hazards model analysis using more efficient sampling method

Abstract

In general, survival data are time-to-event data, such as time to death, time to appearance of a tumor, or time to recurrence of a disease. Models for survival data have frequently been based on the proportional hazards model, proposed by Cox. The Cox model has intensive application in the field of social, medical, behavioral and public health sciences. In this paper we propose a more efficient sampling method of recruiting subjects for survival analysis. We propose using a Moving Extreme Ranked Set Sampling (MERSS) scheme with ranking based on an easy-to-evaluate baseline auxiliary variable known to be associated with survival time. This paper demonstrates that this approach provides a more powerful testing procedure as well as a more efficient estimate of hazard ratio than that based on simple random sampling (SRS). Theoretical derivation and simulation studies are provided. The Iowa 65+ Rural study data are used to illustrate the methods developed in this paper.     

Semiparametric additive marginal regression models for multiple type recurrent events

Recurrent event data are often encountered in biomedical research, for example, recurrent infections or recurrent hospitalizations for patients after renal transplant. In many studies, there are more than one type of events of interest. Cai and Schaube (Lifetime Data Anal 10:121-138, 2004) advocated a proportional marginal rate model for multiple type recurrent event data. In this paper, we propose a general additive marginal rate regression model. Estimating equations approach is used to obtain the estimators of regression coefficients and baseline rate function. We prove the consistency and asymptotic normality of the proposed estimators. The finite sample properties of our estimators are demonstrated by simulations. The proposed methods are applied to the India renal transplant study to examine risk factors for bacterial, fungal and viral infections.     

Nonparametric causal effects based on marginal structural models

A parametric marginal structural model (PMSM) approach to Causal Inference has been favored since the introduction of MSMs by Robins [1998a. Marginal structural models. In: 1997 Proceedings of the American Statistical Association. American Statistical Association, Alexandria, VA, pp. 1–10]. We propose an alternative, nonparametric MSM (NPMSM) approach that extends the definition of causal parameters of interest and causal effects. This approach is appealing in practice as it does not require correct specification of a parametric model but instead relies on a working model which can be willingly misspecified. We propose a methodology for longitudinal data to generate and estimate so-called NPMSM parameters describing so-called nonparametric causal effects and provide insight on how to interpret these parameters causally in practice. Results are illustrated with a point treatment simulation study. The proposed NPMSM approach to Causal Inference is compared to the more typical PMSM approach and we contribute to the general understanding of PMSM estimation by addressing the issue of PMSM misspecification.     

Case-cohort analysis of clusters of recurrent events

The case-cohort sampling, first proposed in Prentice (Biometrika 73:1–11, 1986), is one of the most effective cohort designs for analysis of event occurrence, with the regression model being the typical Cox proportional hazards model. This paper extends to consider the case-cohort design for recurrent events with certain specific clustering feature, which is captured by a properly modified Cox-type self-exciting intensity model. We discuss the advantage of using this model and validate the pseudo-likelihood method. Simulation studies are presented in support of the theory. Application is illustrated with analysis of a bladder cancer data.     

A Statistical Model for Shelf Life Estimation Using Sensory Evaluations Scores

Abstract

This article focuses on the problem of estimating the shelf life of food products by modeling the results coming from sensory evaluations. In such studies, trained panelists are asked to judge food attributes by reference to a scale of numbers (scores varying often from 0 to 6). The usual statistical approach for data analysis is to fit a regression line relating the scores and the time of evaluation. The estimate of the shelf life is obtained by solving the regression equation and replacing the score by a cut-off point (which indicates product “failure”) previously chosen by the food company. The procedure used in these sensory evaluations is such that one never knows the exact “time to failure”. Consequently, data arising from these studies are either right or left censored. We propose a model which incorporates these informations and assumes a Weibull for the underlying distribution of the failure time. Simulation studies were implemented. The approach was used in a real data set coming from sensory evaluations of a dehydrated food product.     

Exponential class of dynamic binary choice panel data models with fixed effects

ABSTRACT

This paper proposes an exponential class of dynamic binary choice panel data models for the analysis of short T (time dimension) large N (cross section dimension) panel data sets that allow for unobserved heterogeneity (fixed effects) to be arbitrarily correlated with the covariates. The paper derives moment conditions that are invariant to the fixed effects which are then used to identify and estimate the parameters of the model. Accordingly, generalized method of moments (GMM) estimators are proposed that are consistent and asymptotically normally distributed at the root-N rate. We also study the conditional likelihood approach and show that under exponential specification, it can identify the effect of state dependence but not the effects of other covariates. Monte Carlo experiments show satisfactory finite sample performance for the proposed estimators and investigate their robustness to misspecification.     

Rank-based multiple change-point detection

Abstract

A nonparametric procedure is proposed to estimate multiple change-points of location changes in a univariate data sequence by using ranks instead of the raw data. While existing rank-based multiple change-point detection methods are mostly based on sequential tests, we treat it as a model selection problem. We derive the corresponding Schwarz’s information criterion for rank-statistics, theoretically prove the consistency of the change-point estimator and use a pruned dynamic programing algorithm to achieve the change-point estimator. Simulation studies show our method’s robustness, effectiveness and efficiency in detecting mean-changes. We also apply the method to a gene dataset as an illustration.     

High breakdown point robust estimators with missing data

In this paper, we propose a new procedure to estimate the distribution of a variable y when there are missing data. To compensate the presence of missing responses, it is assumed that a covariate vector x is observed and that y and x are related by means of a semi-parametric regression model. Observed residuals are combined with predicted values to estimate the missing response distribution. Once the responses distribution is consistently estimated, we can estimate any parameter defined through a continuous functional T using a plug in procedure. We prove that the proposed estimators have high breakdown point.