Prevalent cohort sampling is commonly used to study the natural history of a disease when the disease is rare or it usually takes a long time to observe the failure event. It is known, however, that the collected sample in this situation is not representative of the target population which in turn leads to biased sample risk sets. In addition, when survival times are subject to censoring, the censoring mechanism is informative. In this paper, I propose a pseudo-partial likelihood estimation method for estimating parameters in the Cox proportional hazards model with right-censored and biased sampling data by adjusting sample risk sets. I study the asymptotic properties of the resulting estimator and conduct a simulation study to illustrate its finite sample performance of the proposed method. I also use the proposed method to analyze a set of HIV/AIDS data.
The Scientific Registry of Transplant Recipients (SRTR) system has become a rich resource for understanding the complex mechanisms of graft failure after kidney transplant, a crucial step for allocating organs effectively and implementing appropriate care. As transplant centers that treated patients might strongly confound graft failures, Cox models stratified by centers can eliminate their confounding effects. Also, since recipient age is a proven non-modifiable risk factor, a common practice is to fit models separately by recipient age groups. The moderate sample sizes, relative to the numbe…
Structured Transfer Learning for Survival Risk Stratification in Data-Sparse Clinical Cohorts
National University of Singapore（新加坡国立大学）；Institute for Human Development and Potential, Agency for Science, Technology and Research (A*STAR)（人才发展研究所，科学技术研究局（A*STAR））；Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR)（生物信息学研究所，科学技术研究局（A*STAR））；Department of Biomedical Informatics & Data Science, Yale School of Medicine（耶鲁医学院生物医学信息学与数据科学系）；National Heart & Lung Institute, Imperial College London（帝国理工学院国家心肺研究所）
Polygenic hazard score (PHS) models designed for European ancestry (EUR) individuals provide ample information regarding survival risk discrimination. Incorporating such information can improve the performance of risk discrimination in an internal small-sized non-EUR cohort. However, given that external EUR-based model and internal individual-level data come from different populations, ignoring population heterogeneity can introduce substantial bias. In this paper, we develop a Kullback-Leibler-based Cox model (CoxKL) to integrate internal individual-level time-to-event data with external risk…
Most prediction models that are used in medical research fail to accurately predict health outcomes due to methodological limitations. Using routinely collected patient data, we explore the use of a Cox proportional hazard (PH) model within a latent class framework to model survival of patients with chronic heart failure (CHF). We identify subgroups of patients based on their risk with the aid of available covariates. We allow each subgroup to have its own risk model.We choose an optimum number of classes based on the reported Bayesian information criteria (BIC). We assess the discriminative a…
In this paper, we develop a computationally efficient discrete approximation to log-Gaussian Cox process (LGCP) models for the analysis of spatially aggregated disease count data. Our approach overcomes an inherent limitation of spatial models based on Markov structures, namely that each such model is tied to a specific partition of the study area, and allows for spatially continuous prediction. We compare the predictive performance of our modelling approach with LGCP through a simulation study and an application to primary biliary cirrhosis incidence data in Newcastle-Upon-Tyne, UK. Our resul…
Truncation is a statistical phenomenon that occurs in many time to event studies. For example, autopsy-confirmed studies of neurodegenerative diseases are subject to an inherent left and right truncation, also known as double truncation. When the goal is to study the effect of risk factors on survival, the standard Cox regression model cannot be used when the data is subject to truncation. Existing methods which adjust for both left and right truncation in the Cox regression model require independence between the survival times and truncation times, which may not be a reasonable assumption in …
The shape of the relationship between a continuous exposure variable and a binary disease variable is often central to epidemiologic investigations. This paper investigates a number of issues surrounding inference and the shape of the relationship. Presuming that the relationship can be expressed in terms of regression coefficients and a shape parameter, we investigate how well the shape can be inferred in settings which might typify epidemiologic investigations and risk assessment. We also consider a suitable definition of the median effect of exposure, and investigate how precisely this can …
Institute for Mathematical and Molecular Biomedicine, King’s College London（伦敦国王学院数学与分子生物医学研究所）；King’s College London（伦敦国王学院）；Saddle Point Science Ltd（鞍点科学有限公司）
The Cox proportional hazards model is ubiquitous in the analysis of time-to-event data. However, when the data dimension p is comparable to the sample size $N$, maximum likelihood estimates for its regression parameters are known to be biased or break down entirely due to overfitting. This prompted the introduction of the so-called regularized Cox model. In this paper we use the replica method from statistical physics to investigate the relationship between the true and inferred regression parameters in regularized multivariate Cox regression with L2 regularization, in the regime where both p …
An important task in clinical medicine is the construction of risk prediction models for specific subgroups of patients based on high-dimensional molecular measurements such as gene expression data. Major objectives in modeling high-dimensional data are good prediction performance and feature selection to find a subset of predictors that are truly associated with a clinical outcome such as a time-to-event endpoint. In clinical practice, this task is challenging since patient cohorts are typically small and can be heterogeneous with regard to their relationship between predictors and outcome. W…
Variable selection problem for the nonlinear Cox regression model is considered. In survival analysis, one main objective is to identify the covariates that are associated with the risk of experiencing the event of interest. The Cox proportional hazard model is being used extensively in survival analysis in studying the relationship between survival times and covariates, where the model assumes that the covariate has a log-linear effect on the hazard function. However, this linearity assumption may not be satisfied in practice. In order to extract a representative subset of features, various v…
Capture-recapture methods aim to estimate the size of a closed population on the basis of multiple incomplete enumerations of individuals. In many applications, the individual probability of being recorded is heterogeneous in the population. Previous studies have suggested that it is not possible to reliably estimate the total population size when capture heterogeneity exists. Here we approach population estimation in the presence of capture heterogeneity as a latent length biased nonparametric density estimation problem on the unit interval. We show that in this setting it is generally imposs…
Important objectives in cancer research are the prediction of a patient's risk based on molecular measurements such as gene expression data and the identification of new prognostic biomarkers (e.g. genes). In clinical practice, this is often challenging because patient cohorts are typically small and can be heterogeneous. In classical subgroup analysis, a separate prediction model is fitted using only the data of one specific cohort. However, this can lead to a loss of power when the sample size is small. Simple pooling of all cohorts, on the other hand, can lead to biased results, especially …
We consider estimation of the cumulative incidence function (CIF) in the competing risks Cox model. We study three methods. Methods 1 and 2 are existing methods while Method 3 is a newly-proposed method. Method 3 is constructed so that the sum of the CIF's across all event types at the last observed event time is guaranteed, assuming no ties, to be equal to 1. The performance of the methods is examined in a simulation study, and the methods are illustrated on a data example from the field of computer code comprehension. The newly-proposed Method 3 exhibits performance comparable to that of Met…
Statistical inference after variable selection in Cox models: A simulation study
Mathematical Statistics and Artificial Intelligence in Medicine, University of Augsburg（医学中的数学统计与人工智能，乌尔姆大学）；Center for Advanced Analytics and Predictive Sciences (CAAPS), University of Augsburg（高级分析与预测科学中心（CAAPS），乌尔姆大学）
Time-to-event analysis often relies on prior parametric assumptions, or, if a non-parametric approach is chosen, Cox's model. This is inherently tied to the assumption of proportional hazards, with the analysis potentially invalidated if this assumption is not fulfilled. In addition, most interpretations focus on the hazard ratio, that is often misinterpreted as the relative risk. In this paper, we introduce an alternative to current methodology for assessing a treatment effect in a two-group situation, not relying on the proportional hazards assumption but assuming proportional risks. Precise…
We consider a class of Cox models with time-dependent effects that may be zero over certain unknown time regions or, in short, sparse time-varying effects. The model is particularly useful for biomedical studies as it conveniently depicts the gradual evolution of effects of risk factors on survival. Statistically, estimating and drawing inference on infinite dimensional functional parameters with sparsity (e.g., time-varying effects with zero-effect time intervals) present enormous challenges. To address them, we propose a new soft-thresholding operator for modeling sparse, piecewise smooth an…
In contrast to the popular Cox model which presents a multiplicative covariate effect specification on the time to event hazards, the semiparametric additive risks model (ARM) offers an attractive additive specification, allowing for direct assessment of the changes or the differences in the hazard function for changing value of the covariates. The ARM is a flexible model, allowing the estimation of both time-independent and time-varying covariates. It has a nonparametric component and a regression component identified by a finite-dimensional parameter. This chapter presents an efficient appro…
Risk assessment tools are widely used around the country to inform decision making within the criminal justice system. Recently, considerable attention has been devoted to the question of whether such tools may suffer from racial bias. In this type of assessment, a fundamental issue is that the training and evaluation of the model is based on a variable (arrest) that may represent a noisy version of an unobserved outcome of more central interest (offense). We propose a sensitivity analysis framework for assessing how assumptions on the noise across groups affect the predictive bias properties …
Information from various data sources is increasingly available nowadays. However, some of the data sources may produce biased estimation due to commonly encountered biased sampling, population heterogeneity, or model misspecification. This calls for statistical methods to combine information in the presence of biased sources. In this paper, a robust data fusion-extraction method is proposed. The method can produce a consistent estimator of the parameter of interest even if many of the data sources are biased. The proposed estimator is easy to compute and only employs summary statistics, and h…
In this work we develop methods for privatizing spatial location data, such as spatial locations of individual disease cases. We propose two novel Bayesian methods for generating synthetic location data based on log-Gaussian Cox processes (LGCPs). We show that conditional predictive ordinate (CPO) estimates can easily be obtained for point process data. We construct a novel risk metric that utilizes CPO estimates to evaluate individual disclosure risks. We adapt the propensity mean square error (pMSE) data utility metric for LGCPs. We demonstrate that our synthesis methods offer an improved ri…
Many time-to-event studies are complicated by the presence of competing risks. Such data are often analyzed using Cox models for the cause specific hazard function or Fine-Gray models for the subdistribution hazard. In practice regression relationships in competing risks data with either strategy are often complex and may include nonlinear functions of covariates, interactions, high-dimensional parameter spaces and nonproportional cause specific or subdistribution hazards. Model misspecification can lead to poor predictive performance. To address these issues, we propose a novel approach to fl…
Manipulating a Continuous Instrumental Variable in an Observational Study of Premature Babies: Algorithm, Partial Identification Bounds, and Inference under Randomization and Biased Randomization Assumptions
Multinomial logistic regression models allow one to predict the risk of a categorical outcome with more than 2 categories. When developing such a model, researchers should ensure the number of participants (n) is appropriate relative to the number of events (E.k) and the number of predictor parameters (p.k) for each category k. We propose three criteria to determine the minimum n required in light of existing criteria developed for binary outcomes. The first criteria aims to minimise the model overfitting. The second aims to minimise the difference between the observed and adjusted R2 Nagelker…
