Exposure Stratified Case-Cohort Designs

A variant of the case-cohort design is proposed for the situation in which a correlate of the exposure (or prognostic factor) of interest is available for all cohort members, and exposure information is to be collected for a case-cohort sample. The cohort is stratified according to the correlate, and the subcohort is selected by stratified random sampling. A number of possible methods for the analysis of such exposure stratified case-cohort samples are presented, some of their statistical properties developed, and approximate relative efficiency and optimal allocation to the strata discussed. The methods are compared to each other, and to randomly sampled case-cohort studies, in a limited computer simulation study. We found that all of the proposed analysis methods performed well and were more efficient than a randomly sampled case-cohort study.     

Stratified proportional subdistribution hazards model with covariate-adjusted censoring weight for case-cohort studies

The case-cohort study design is widely used to reduce cost when collecting expensive covariates in large cohort studies with survival or competing risks outcomes. A case-cohort study dataset consists of two parts: (a) a random sample and (b) all cases or failures from a specific cause of interest. Clinicians often assess covariate effects on competing risks outcomes. The proportional subdistribution hazards model directly evaluates the effect of a covariate on the cumulative incidence function under the non-covariate-dependent censoring assumption for the full cohort study. However, the non-covariate-dependent censoring assumption is often violated in many biomedical studies. In this article, we propose a proportional subdistribution hazards model for case-cohort studies with stratified data with covariate-adjusted censoring weight. We further propose an efficient estimator when extra information from the other causes is available under case-cohort studies. The proposed estimators are shown to be consistent and asymptotically normal. Simulation studies show (a) the proposed estimator is unbiased when the censoring distribution depends on covariates and (b) the proposed efficient estimator gains estimation efficiency when using extra information from the other causes. We analyze a bone marrow transplant dataset and a coronary heart disease dataset using the proposed method.     

An adaptive allocation sampling design for which the conventional stratified estimator is an appropriate estimator

Adaptive allocations in stratified sampling design are suitable for studying Biological and Environmental populations. Biologists tend to use the conventional stratified estimator for an adaptive allocation sampling design in spite of its adaptive nature. In this paper, we have introduced an adaptive allocation sampling design for which the conventional stratified estimator has some desired statistical properties. We conduct a simulation study on a real population. The results show that the conventional stratified estimator for the introduced adaptive allocation sampling design is more efficient than other available estimators.     

Additive risk model with case-cohort sampled current status data

Two-phase stratified sampling has been extensively used in large epidemiologic studies as a way of reducing costs associated with assembling covariate histories and enlarging relative sample sizes of the most informative subgroups. In this article, we investigate case-cohort sampled current status data under the additive risk model assumption. We describe a class of estimating equations, each depending on a different prevalence ratio estimate. Asymptotic properties of the proposed estimators and inference based on the “m out of n” nonparametric bootstrap are investigated. A small simulation study is employed to evaluate the finite sample performance and relative efficiency of the proposed estimators.     

Stratified Case-Cohort Analysis of General Cohort Sampling Designs

Abstract.  It is shown that variance estimates for regression coefficients in exposure-stratified case-cohort studies (Borgan et al ., Lifetime Data Anal., 6, 2000, 39–58) can easily be obtained from influence terms routinely calculated in the standard software for Cox regression. By allowing for post-stratification on outcome we also place the estimators proposed by Chen ( J. R. Statist. Soc. Ser. B , 63, 2001, 791–809) for a general class of cohort sampling designs within the Borgan et al. 's framework, facilitating simple variance estimation for these designs. Finally, the Chen approach is extended to accommodate stratified designs with surrogate variables available for all cohort members, such as stratified case-cohort and counter-matching designs.     

Influence Function Based Variance Estimation and Missing Data Issues in Case-Cohort Studies

Recognizing that the efficiency in relative risk estimation for the Cox proportional hazards model is largely constrained by the total number of cases, Prentice (1986) proposed the case-cohort design in which covariates are measured on all cases and on a random sample of the cohort. Subsequent to Prentice, other methods of estimation and sampling have been proposed for these designs. We formalize an approach to variance estimation suggested by Barlow (1994), and derive a robust variance estimator based on the influence function. We consider the applicability of the variance estimator to all the proposed case-cohort estimators, and derive the influence function when known sampling probabilities in the estimators are replaced by observed sampling fractions. We discuss the modifications required when cases are missing covariate information. The missingness may occur by chance, and be completely at random; or may occur as part of the sampling design, and depend upon other observed covariates. We provide an adaptation of S-plus code that allows estimating influence function variances in the presence of such missing covariates. Using examples from our current case-cohort studies on esophageal and gastric cancer, we illustrate how our results our useful in solving design and analytic issues that arise in practice.     

A regularized variable selection procedure in additive hazards model with stratified case-cohort design

Case-cohort designs are commonly used in large epidemiological studies to reduce the cost associated with covariate measurement. In many such studies the number of covariates is very large. An efficient variable selection method is needed for case-cohort studies where the covariates are only observed in a subset of the sample. Current literature on this topic has been focused on the proportional hazards model. However, in many studies the additive hazards model is preferred over the proportional hazards model either because the proportional hazards assumption is violated or the additive hazards model provides more relevent information to the research question. Motivated by one such study, the Atherosclerosis Risk in Communities (ARIC) study, we investigate the properties of a regularized variable selection procedure in stratified case-cohort design under an additive hazards model with a diverging number of parameters. We establish the consistency and asymptotic normality of the penalized estimator and prove its oracle property. Simulation studies are conducted to assess the finite sample performance of the proposed method with a modified cross-validation tuning parameter selection methods. We apply the variable selection procedure to the ARIC study to demonstrate its practical use.     

Analysis of two-phase sampling data with semiparametric additive hazards models

Under the case-cohort design introduced by Prentice (Biometrica 73:1–11, 1986), the covariate histories are ascertained only for the subjects who experience the event of interest (i.e., the cases) during the follow-up period and for a relatively small random sample from the original cohort (i.e., the subcohort). The case-cohort design has been widely used in clinical and epidemiological studies to assess the effects of covariates on failure times. Most statistical methods developed for the case-cohort design use the proportional hazards model, and few methods allow for time-varying regression coefficients. In addition, most methods disregard data from subjects outside of the subcohort, which can result in inefficient inference. Addressing these issues, this paper proposes an estimation procedure for the semiparametric additive hazards model with case-cohort/two-phase sampling data, allowing the covariates of interest to be missing for cases as well as for non-cases. A more flexible form of the additive model is considered that allows the effects of some covariates to be time varying while specifying the effects of others to be constant. An augmented inverse probability weighted estimation procedure is proposed. The proposed method allows utilizing the auxiliary information that correlates with the phase-two covariates to improve efficiency. The asymptotic properties of the proposed estimators are established. An extensive simulation study shows that the augmented inverse probability weighted estimation is more efficient than the widely adopted inverse probability weighted complete-case estimation method. The method is applied to analyze data from a preventive HIV vaccine efficacy trial.     

Regression analysis of case-cohort studies in the presence of dependent interval censoring

The case-cohort design is widely used as a means of reducing the cost in large cohort studies, especially when the disease rate is low and covariate measurements may be expensive, and has been discussed by many authors. In this paper, we discuss regression analysis of case-cohort studies that produce interval-censored failure time with dependent censoring, a situation for which there does not seem to exist an established approach. For inference, a sieve inverse probability weighting estimation procedure is developed with the use of Bernstein polynomials to approximate the unknown baseline cumulative hazard functions. The proposed estimators are shown to be consistent and the asymptotic normality of the resulting regression parameter estimators is established. A simulation study is conducted to assess the finite sample properties of the proposed approach and indicates that it works well in practical situations. The proposed method is applied to an HIV/AIDS case-cohort study that motivated this investigation.     

Quantile regression for competing risks analysis under case-cohort design

The case-cohort design brings cost reduction in large cohort studies. In this paper, we consider a nonlinear quantile regression model for censored competing risks under the case-cohort design. Two different estimation equations are constructed with or without the covariates information of other risks included, respectively. The large sample properties of the estimators are obtained. The asymptotic covariances are estimated by using a fast resampling method, which is useful to consider further inferences. The finite sample performance of the proposed estimators is assessed by simulation studies. Also a real example is used to demonstrate the application of the proposed methods.     

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.     

Statistical inference for generalized case-cohort design under the proportional hazards model with parameter constraints

ABSTRACT

The generalized case-cohort design is widely used in large cohort studies to reduce the cost and improve the efficiency. Taking prior information of parameters into consideration in modeling process can further raise the inference efficiency. In this paper, we consider fitting proportional hazards model with constraints for generalized case-cohort studies. We establish a working likelihood function for the estimation of model parameters. The asymptotic properties of the proposed estimator are derived via the Karush-Kuhn-Tucker conditions, and their finite properties are assessed by simulation studies. A modified minorization-maximization algorithm is developed for the numerical calculation of the constrained estimator. An application to a Wilms tumor study demonstrates the utility of the proposed method in practice.     

Finite mixture of regression models for a stratified sample

Despite the popularity and importance, there is limited work on modelling data which come from complex survey design using finite mixture models. In this work, we explored the use of finite mixture regression models when the samples were drawn using a complex survey design. In particular, we considered modelling data collected based on stratified sampling design. We developed a new design-based inference where we integrated sampling weights in the complete-data log-likelihood function. The expectation–maximisation algorithm was developed accordingly. A simulation study was conducted to compare the new methodology with the usual finite mixture of a regression model. The comparison was done using bias-variance components of mean square error. Additionally, a simulation study was conducted to assess the ability of the Bayesian information criterion to select the optimal number of components under the proposed modelling approach. The methodology was implemented on real data with good results.     

Calibration estimator of population mean under stratified ranked set sampling design

Calibration method adjusts the original design weights to improve the estimates by using auxiliary information. In this article we have proposed new calibration estimators under stratified ranked set sampling design and derive the estimator of variance of calibration estimator. A simulation study is carried out to see the performance of proposed estimators.     

A Comparison Of Two Adaptive Sampling Designs

Stratified sampling is a technique commonly used for ecological surveys. In this study there appears to be little gain in using a stratified design with adaptive cluster sampling. Two-phase adaptive sampling is preferable to adaptive cluster sampling. Even though two-phase adaptive sampling can give biased estimates, it is found that two-phase adaptive sampling has a lower MSE than adaptive cluster sampling for most populations.     

Design‐Based Inference in a Mixture Model for Ordinal Variables for a Two Stage Stratified Design

In this paper we present methods for inference on data selected by a complex sampling design for a class of statistical models for the analysis of ordinal variables. Specifically, assuming that the sampling scheme is not ignorable, we derive for the class of cub models (Combination of discrete Uniform and shifted Binomial distributions) variance estimates for a complex two stage stratified sample. Both Taylor linearization and repeated replication variance estimators are presented. We also provide design‐based test diagnostics and goodness‐of‐fit measures. We illustrate by means of real data analysis the differences between survey‐weighted and unweighted point estimates and inferences for cub model parameters.     

Gap-based inverse sampling

We present a new inverse sampling design for surveys of rare events, Gap-Based Inverse Sampling. In the design, sampling stops if after a predetermined interval, or gap, no new rare events are found. The length of the gap that follows after finding a rare event is used as a way of limiting sample effort. We present stopping rules using decisions based on the gap length, the total number of rare events found, and a fixed upper limit of survey effort. We illustrate the use of the design with stratified sampling of two biological populations. The design uses the intuitive behavior of a field biologist in stratified sampling, where if in a stratum nothing is found after a long search, the field surveyor would like to consider the stratum is empty and stop searching. Our design has appeal for surveying rare events (for example, a rare species) with stratified sampling where there are likely to be some completely empty strata.     

Stratified sampling using double samples

Usual stratified sampling design assume that one is able to draw units directly from given strata. If this is not possible, one can use the following double sampling procedure: First take a large simple random sample out of the whole population and find out, to which stratum each sample unit belongs. Out of these chosen units take a second stratified sample. In this paper unbiased estimators for this procedure in the cases of known (part I) and unknown (part II) stratum weights are proposed for sampling with replacement and sampling without replacement and their variances are evaluated.     

Joint modeling of longitudinal and survival data with the Cox model and two-phase sampling

A common objective of cohort studies and clinical trials is to assess time-varying longitudinal continuous biomarkers as correlates of the instantaneous hazard of a study endpoint. We consider the setting where the biomarkers are measured in a designed sub-sample (i.e., case-cohort or two-phase sampling design), as is normative for prevention trials. We address this problem via joint models, with underlying biomarker trajectories characterized by a random effects model and their relationship with instantaneous risk characterized by a Cox model. For estimation and inference we extend the conditional score method of Tsiatis and Davidian (Biometrika 88(2):447–458, 2001) to accommodate the two-phase biomarker sampling design using augmented inverse probability weighting with nonparametric kernel regression. We present theoretical properties of the proposed estimators and finite-sample properties derived through simulations, and illustrate the methods with application to the AIDS Clinical Trials Group 175 antiretroviral therapy trial. We discuss how the methods are useful for evaluating a Prentice surrogate endpoint, mediation, and for generating hypotheses about biological mechanisms of treatment efficacy.     

Efficient estimators for adaptive stratified sequential sampling

In stratified sampling, methods for the allocation of effort among strata usually rely on some measure of within-stratum variance. If we do not have enough information about these variances, adaptive allocation can be used. In adaptive allocation designs, surveys are conducted in two phases. Information from the first phase is used to allocate the remaining units among the strata in the second phase. Brown et al. [Adaptive two-stage sequential sampling, Popul. Ecol. 50 (2008), pp. 239–245] introduced an adaptive allocation sampling design – where the final sample size was random – and an unbiased estimator. Here, we derive an unbiased variance estimator for the design, and consider a related design where the final sample size is fixed. Having a fixed final sample size can make survey-planning easier. We introduce a biased Horvitz–Thompson type estimator and a biased sample mean type estimator for the sampling designs. We conduct two simulation studies on honey producers in Kurdistan and synthetic zirconium distribution in a region on the moon. Results show that the introduced estimators are more efficient than the available estimators for both variable and fixed sample size designs, and the conventional unbiased estimator of stratified simple random sampling design. In order to evaluate efficiencies of the introduced designs and their estimator furthermore, we first review some well-known adaptive allocation designs and compare their estimator with the introduced estimators. Simulation results show that the introduced estimators are more efficient than available estimators of these well-known adaptive allocation designs.