Variable selection for case-cohort studies with failure time outcome.
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ABSTRACT:
SUBMITTER: Ni AI
PROVIDER: S-EPMC5436496 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The case-cohort design is an economical approach to estimate the effect of risk factors on the survival outcome when collecting exposure information or covariates on all patients is expensive in a large cohort study. Variables often have group structure such as categorical variables and highly correlated continuous variables. The existing literature for case-cohort data is limited to identifying non-zero variables at individual level only. In this article, we propose a bi-level variable selection method to select non-zero group and within-group variables for case-cohort data when variables have group structure. The proposed method allows the number of variables to diverge as the sample size increases. The asymptotic properties of the estimator including bi-level variable selection consistency and the asymptotic normality are shown. We also conduct simulations to compare our proposed method with some existing method and apply them to the Busselton Health data.
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Project description:The case-cohort design has been widely used as a means of cost reduction in assembling or measuring expensive covariates in large cohort studies. The existing literature on the case-cohort design is mainly focused on right-censored data. In practice, however, the failure time is often subject to interval-censoring; it is known only to fall within some random time interval. In this paper, we consider the case-cohort study design for interval-censored failure time and develop a sieve semiparametric likelihood approach for analyzing data from this design under the proportional hazards model. We construct the likelihood function using inverse probability weighting and build the sieves with Bernstein polynomials. The consistency and asymptotic normality of the resulting regression parameter estimator are established and a weighted bootstrap procedure is considered for variance estimation. Simulations show that the proposed method works well for practical situations, and an application to real data is provided.
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Project description:The case-cohort study design is an effective way to reduce cost of assembling and measuring expensive covariates in large cohort studies. Recently, several weighted estimators were proposed for the case-cohort design when multiple diseases are of interest. However, these existing weighted estimators do not make effective use of the covariate information available in the whole cohort. Furthermore, the auxiliary information for the expensive covariates, which may be available in the studies, cannot be incorporated directly. In this article, we propose a class of updated-estimators. We show that, by making effective use of the whole cohort information, the proposed updated-estimators are guaranteed to be more efficient than the existing weighted estimators asymptotically. Furthermore, they are flexible to incorporate the auxiliary information whenever available. The advantages of the proposed updated-estimators are demonstrated in simulation studies and a real data analysis.
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Project description:In high throughput genomic studies, an important goal is to identify a small number of genomic markers that are associated with development and progression of diseases. A representative example is microarray prognostic studies, where the goal is to identify genes whose expressions are associated with disease free or overall survival. Because of the high dimensionality of gene expression data, standard survival analysis techniques cannot be directly applied. In addition, among the thousands of genes surveyed, only a subset are disease-associated. Gene selection is needed along with estimation. In this article, we model the relationship between gene expressions and survival using the accelerated failure time (AFT) models. We use the bridge penalization for regularized estimation and gene selection. An efficient iterative computational algorithm is proposed. Tuning parameters are selected using V-fold cross validation. We use a resampling method to evaluate the prediction performance of bridge estimator and the relative stability of identified genes. We show that the proposed bridge estimator is selection consistent under appropriate conditions. Analysis of two lymphoma prognostic studies suggests that the bridge estimator can identify a small number of genes and can have better prediction performance than the Lasso.
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Project description:BackgroundIn many applications of instrumental variable (IV) methods, the treatments of interest are intrinsically time-varying and outcomes of interest are failure time outcomes. A common example is Mendelian randomization (MR), which uses genetic variants as proposed IVs. In this article, we present a novel application of g-estimation of structural nested cumulative failure models (SNCFTMs), which can accommodate multiple measures of a time-varying treatment when modelling a failure time outcome in an IV analysis.MethodsA SNCFTM models the ratio of two conditional mean counterfactual outcomes at time k under two treatment strategies which differ only at an earlier time m. These models can be extended to accommodate inverse probability of censoring weights, and can be applied to case-control data. We also describe how the g-estimates of the SNCFTM parameters can be used to calculate marginal cumulative risks under nondynamic treatment strategies. We examine the performance of this method using simulated data, and present an application of these models by conducting an MR study of alcohol intake and endometrial cancer using longitudinal observational data from the Nurses' Health Study.ResultsOur simulations found that estimates from SNCFTMs which used an IV approach were similar to those obtained from SNCFTMs which adjusted for confounders, and similar to those obtained from the g-formula approach when the outcome was rare. In our data application, the cumulative risk of endometrial cancer from age 45 to age 72 under the "never drink" strategy (4.0%) was similar to that under the "always ½ drink per day" strategy (4.3%).ConclusionsSNCFTMs can be used to conduct MR and other IV analyses with time-varying treatments and failure time outcomes.
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Project description: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.
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Project description:Methodological advancements, including propensity score methods, have resulted in improved unbiased estimation of treatment effects from observational data. Traditionally, a "throw in the kitchen sink" approach has been used to select covariates for inclusion into the propensity score, but recent work shows including unnecessary covariates can impact both the bias and statistical efficiency of propensity score estimators. In particular, the inclusion of covariates that impact exposure but not the outcome, can inflate standard errors without improving bias, while the inclusion of covariates associated with the outcome but unrelated to exposure can improve precision. We propose the outcome-adaptive lasso for selecting appropriate covariates for inclusion in propensity score models to account for confounding bias and maintaining statistical efficiency. This proposed approach can perform variable selection in the presence of a large number of spurious covariates, that is, covariates unrelated to outcome or exposure. We present theoretical and simulation results indicating that the outcome-adaptive lasso selects the propensity score model that includes all true confounders and predictors of outcome, while excluding other covariates. We illustrate covariate selection using the outcome-adaptive lasso, including comparison to alternative approaches, using simulated data and in a survey of patients using opioid therapy to manage chronic pain.
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Project description:BackgroundAccurate detection and estimation of true exposure-outcome associations is important in aetiological analysis; when there are multiple potential exposure variables of interest, methods for detecting the subset of variables most likely to have true associations with the outcome of interest are required. Case-cohort studies often collect data on a large number of variables which have not been measured in the entire cohort (e.g. panels of biomarkers). There is a lack of guidance on methods for variable selection in case-cohort studies.MethodsWe describe and explore the application of three variable selection methods to data from a case-cohort study. These are: (i) selecting variables based on their level of significance in univariable (i.e. one-at-a-time) Prentice-weighted Cox regression models; (ii) stepwise selection applied to Prentice-weighted Cox regression; and (iii) a two-step method which applies a Bayesian variable selection algorithm to obtain posterior probabilities of selection for each variable using multivariable logistic regression followed by effect estimation using Prentice-weighted Cox regression.ResultsAcross nine different simulation scenarios, the two-step method demonstrated higher sensitivity and lower false discovery rate than the one-at-a-time and stepwise methods. In an application of the methods to data from the EPIC-InterAct case-cohort study, the two-step method identified an additional two fatty acids as being associated with incident type 2 diabetes, compared with the one-at-a-time and stepwise methods.ConclusionsThe two-step method enables more powerful and accurate detection of exposure-outcome associations in case-cohort studies. An R package is available to enable researchers to apply this method.
| S-EPMC5913627 | biostudies-literature
Project description:Case-cohort (Prentice, 1986) and nested case-control (Thomas, 1977) designs have been widely used as a cost-effective alternative to the full-cohort design. In this article, we propose an efficient likelihood-based estimation method for the accelerated failure time model under case-cohort and nested case-control designs. An EM algorithm is developed to maximize the likelihood function and a kernel smoothing technique is adopted to facilitate the estimation in the M-step of the EM algorithm. We show that the proposed estimators for the regression coefficients are consistent and asymptotically normal. The asymptotic variance of the estimators can be consistently estimated using an EM-aided numerical differentiation method. Simulation studies are conducted to evaluate the finite-sample performance of the estimators and an application to a Wilms tumor data set is also given to illustrate the methodology.
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Project description:For the analysis of ultrahigh-dimensional data, the first step is often to perform screening and feature selection to effectively reduce the dimensionality while retaining all the active or relevant variables with high probability. For this, many methods have been developed under various frameworks but most of them only apply to complete data. In this paper, we consider an incomplete data situation, case II interval-censored failure time data, for which there seems to be no screening procedure. Basing on the idea of cumulative residual, a model-free or nonparametric method is developed and shown to have the sure independent screening property. In particular, the approach is shown to tend to rank the active variables above the inactive ones in terms of their association with the failure time of interest. A simulation study is conducted to demonstrate the usefulness of the proposed method and, in particular, indicates that it works well with general survival models and is capable of capturing the nonlinear covariates with interactions. Also the approach is applied to a childhood cancer survivor study that motivated this investigation.
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