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Register a new userPenalized integrative analysis under the accelerated failure time model
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Qingzhao Zhang PhD
Publication date
2015
fields
Mathematical Statistics
and research's language is
English
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For survival data with high-dimensional covariates, results generated in the analysis of a single dataset are often unsatisfactory because of the small sample size. Integrative analysis pools raw data from multiple independent studies with comparable designs, effectively increases sample size, and has better performance than meta-analysis and single-dataset analysis. In this study, we conduct integrative analysis of survival data under the accelerated failure time (AFT) model. The sparsity structures of multiple datasets are described using the homogeneity and heterogeneity models. For variable selection under the homogeneity model, we adopt group penalization approaches. For variable selection under the heterogeneity model, we use composite penalization and sparse group penalization approaches. As a major advancement from the existing studies, the asymptotic selection and estimation properties are rigorously established. Simulation study is conducted to compare different penalization methods and against alternatives. We also analyze four lung cancer prognosis datasets with gene expression measurements.
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Network meta-analysis (NMA) allows the combination of direct and indirect evidence from a set of randomized clinical trials. Performing NMA using individual patient data (IPD) is considered as a gold standard approach as it provides several advantages over NMA based on aggregate data. For example, it allows to perform advanced modelling of covariates or covariate-treatment interactions. An important issue in IPD NMA is the selection of influential parameters among terms that account for inconsistency, covariates, covariate-by-treatment interactions or non-proportionality of treatments effect for time to event data. This issue has not been deeply studied in the literature yet and in particular not for time-to-event data. A major difficulty is to jointly account for between-trial heterogeneity which could have a major influence on the selection process. The use of penalized generalized mixed effect model is a solution, but existing implementations have several shortcomings and an important computational cost that precludes their use for complex IPD NMA. In this article, we propose a penalized Poisson regression model to perform IPD NMA of time-to-event data. It is based only on fixed effect parameters which improve its computational cost over the use of random effects. It could be easily implemented using existing penalized regression package. Computer code is shared for implementation. The methods were applied on simulated data to illustrate the importance to take into account between trial heterogeneity during the selection procedure. Finally, it was applied to an IPD NMA of overall survival of chemotherapy and radiotherapy in nasopharyngeal carcinoma.
The penalized Cox proportional hazard model is a popular analytical approach for survival data with a large number of covariates. Such problems are especially challenging when covariates vary over follow-up time (i.e., the covariates are time-dependent). The standard R packages for fully penalized Cox models cannot currently incorporate time-dependent covariates. To address this gap, we implement a variant of gradient descent algorithm (proximal gradient descent) for fitting penalized Cox models. We apply our implementation to real and simulated data sets.
Model fitting often aims to fit a single model, assuming that the imposed form of the model is correct. However, there may be multiple possible underlying explanatory patterns in a set of predictors that could explain a response. Model selection without regarding model uncertainty can fail to bring these patterns to light. We present multi-model penalized regression (MMPR) to acknowledge model uncertainty in the context of penalized regression. In the penalty form explored here, we examine how different settings can promote either shrinkage or sparsity of coefficients in separate models. The method is tuned to explicitly limit model similarity. A choice of penalty form that enforces variable selection is applied to predict stacking fault energy (SFE) from steel alloy composition. The aim is to identify multiple models with different subsets of covariates that explain a single type of response.
For data with high-dimensional covariates but small to moderate sample sizes, the analysis of single datasets often generates unsatisfactory results. The integrative analysis of multiple independent datasets provides an effective way of pooling information and outperforms single-dataset analysis and some alternative multi-datasets approaches including meta-analysis. Under certain scenarios, multiple datasets are expected to share common important covariates, that is, the multiple models have similarity in sparsity structures. However, the existing methods do not have a mechanism to {it promote} the similarity of sparsity structures in integrative analysis. In this study, we consider penalized variable selection and estimation in integrative analysis. We develop an $L_0$-penalty based approach, which is the first to explicitly promote the similarity of sparsity structures. Computationally it is realized using a coordinate descent algorithm. Theoretically it has the much desired consistency properties. In simulation, it significantly outperforms the competing alternative when the models in multiple datasets share common important covariates. It has better or similar performance as the alternative when the sparsity structures share no similarity. Thus it provides a safe choice for data analysis. Applying the proposed method to three lung cancer datasets with gene expression measurements leads to models with significantly more similar sparsity structures and better prediction performance.
We propose a distributed quadratic inference function framework to jointly estimate regression parameters from multiple potentially heterogeneous data sources with correlated vector outcomes. The primary goal of this joint integrative analysis is to estimate covariate effects on all outcomes through a marginal regression model in a statistically and computationally efficient way. We develop a data integration procedure for statistical estimation and inference of regression parameters that is implemented in a fully distributed and parallelized computational scheme. To overcome computational and modeling challenges arising from the high-dimensional likelihood of the correlated vector outcomes, we propose to analyze each data source using Qu, Lindsay and Li (2000)s quadratic inference functions, and then to jointly reestimate parameters from each data source by accounting for correlation between data sources using a combined meta-estimator in a similar spirit to Hansen (1982)s generalised method of moments. We show both theoretically and numerically that the proposed method yields efficiency improvements and is computationally fast. We illustrate the proposed methodology with the joint integrative analysis of the association between smoking and metabolites in a large multi-cohort study and provide an R package for ease of implementation.
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