arXiv subjects

Malka Gorfine

Publications and source records attributed to Malka Gorfine.

32 records · Page 2Linked to original sources

arXiv2020

Causal inference for semi-competing risks data

An emerging challenge for time-to-event data is studying semi-competing risks, namely when two event times are of interest: a non-terminal event time (e.g. age at disease diagnosis), and a terminal event time (e.g. age at death). The non-terminal event is observed only if it precedes the terminal event, which may occur before or after the non-terminal event. Studying treatment or intervention effects on the dual event times is complicated because for some units, the non-terminal event may occur under one treatment value but not under the other. Until recently, existing approaches (e.g., the survivor average causal effect) generally disregarded the time-to-event nature of both outcomes. More recent research focused on principal strata effects within time-varying populations under Bayesian approaches. In this paper, we propose alternative non time-varying estimands, based on a single stratification of the population. We present a novel assumption utilizing the time-to-event nature of the data, which is weaker than the often-invoked monotonicity assumption. We derive results on partial identifiability, suggest a sensitivity analysis approach, and give conditions under which full identification is possible. Finally, we present non-parametric and semi-parametric estimation methods for right-censored data.

stat.ME↗

arXiv2020

Efficient Study Design with Multiple Measurement Instruments

Outcomes from studies assessing exposure often use multiple measurements. In previous work, using a model first proposed by Buonoccorsi (1991), we showed that combining direct (e.g. biomarkers) and indirect (e.g. self-report) measurements provides a more accurate picture of true exposure than estimates obtained when using a single type of measurement. In this article, we propose a valuable tool for efficient design of studies that include both direct and indirect measurements of a relevant outcome. Based on data from a pilot or preliminary study, the tool, which is available online as a shiny app \citep{shinyR}, can be used to compute: (1) the sample size required for a statistical power analysis, while optimizing the percent of participants who should provide direct measures of exposure (biomarkers) in addition to the indirect (self-report) measures provided by all participants; (2) the ideal number of replicates; and (3) the allocation of resources to intervention and control arms. In addition we show how to examine the sensitivity of results to underlying assumptions. We illustrate our analysis using studies of tobacco smoke exposure and nutrition. In these examples, a near-optimal allocation of the resources can be found even if the assumptions are not precise.

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arXiv2019

$K$-sample omnibus non-proportional hazards tests based on right-censored data

This work presents novel and powerful tests for comparing non-proportional hazard functions, based on sample-space partitions. Right censoring introduces two major difficulties which make the existing sample-space partition tests for uncensored data non-applicable: (i) the actual event times of censored observations are unknown; and (ii) the standard permutation procedure is invalid in case the censoring distributions of the groups are unequal. We overcome these two obstacles, introduce invariant tests, and prove their consistency. Extensive simulations reveal that under non-proportional alternatives, the proposed tests are often of higher power compared with existing popular tests for non-proportional hazards. Efficient implementation of our tests is available in the R package KONPsurv, which can be freely downloaded from {https://github.com/matan-schles/KONPsurv

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arXiv2019

Semiparametric Analysis of the Proportional Likelihood Ratio Model and Omnibus Estimation Procedure

We provide a semi-parametric analysis for the proportional likelihood ratio model, proposed by Luo & Tsai (2012). We study the tangent spaces for both the parameter of interest and the nuisance parameter, and obtain an explicit expression for the efficient score function. We propose a family of Z-estimators based on the score functions, including an approximated efficient estimator. Using inverse probability weighting, the proposed estimators can also be applied to different missing-data mechanisms, such as right censored data and non-random sampling. A simulation study that illustrates the finite-sample performance of the estimators is presented.

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arXiv2019

Marginalized Frailty-Based Illness-Death Model: Application to the UK-Biobank Survival Data

The UK Biobank is a large-scale health resource comprising genetic, environmental and medical information on approximately 500,000 volunteer participants in the UK, recruited at ages 40--69 during the years 2006--2010. The project monitors the health and well-being of its participants. This work demonstrates how these data can be used to estimate in a semi-parametric fashion the effects of genetic and environmental risk factors on the hazard functions of various diseases, such as colorectal cancer. An illness-death model is adopted, which inherently is a semi-competing risks model, since death can censor the disease, but not vice versa. Using a shared-frailty approach to account for the dependence between time to disease diagnosis and time to death, we provide a new illness-death model that assumes Cox models for the marginal hazard functions. The recruitment procedure used in this study introduces delayed entry to the data. An additional challenge arising from the recruitment procedure is that information coming from both prevalent and incident cases must be aggregated. Lastly, we do not observe any deaths prior to the minimal recruitment age, 40. In this work we provide an estimation procedure for our new illness-death model that overcomes all the above challenges.

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arXiv2018

An improved fully nonparametric estimator of the marginal survival function based on case-control clustered data

A case-control family study is a study where individuals with a disease of interest (case probands) and individuals without the disease (control probands) are randomly sampled from a well-defined population. Possibly right-censored age at onset and disease status are observed for both probands and their relatives. Correlation among the outcomes within a family is induced by factors such as inherited genetic susceptibility, shared environment, and common behavior patterns. For this setting, we present a nonparametric estimator of the marginal survival function, based on local linear estimation of conditional survival functions. Asymptotic theory for the estimator is provided, and simulation results are presented showing that the method performs well. The method is illustrated on data from a prostate cancer study. Keywords: case-control; family study; multivariate survival; nonparametric estimator; local linear

stat.ME↗

arXiv2018

General Semiparametric Shared Frailty Model Estimation and Simulation with frailtySurv

The R package frailtySurv for simulating and fitting semi-parametric shared frailty models is introduced. Package frailtySurv implements semi-parametric consistent estimators for a variety of frailty distributions, including gamma, log-normal, inverse Gaussian and power variance function, and provides consistent estimators of the standard errors of the parameters' estimators. The parameters' estimators are asymptotically normally distributed, and therefore statistical inference based on the results of this package, such as hypothesis testing and confidence intervals, can be performed using the normal distribution. Extensive simulations demonstrate the flexibility and correct implementation of the estimator. Two case studies performed with publicly available datasets demonstrate applicability of the package. In the Diabetic Retinopathy Study, the onset of blindness is clustered by patient, and in a large hard drive failure dataset, failure times are thought to be clustered by the hard drive manufacturer and model.

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arXiv2015

Consistent distribution-free $K$-sample and independence tests for univariate random variables

A popular approach for testing if two univariate random variables are statistically independent consists of partitioning the sample space into bins, and evaluating a test statistic on the binned data. The partition size matters, and the optimal partition size is data dependent. While for detecting simple relationships coarse partitions may be best, for detecting complex relationships a great gain in power can be achieved by considering finer partitions. We suggest novel consistent distribution-free tests that are based on summation or maximization aggregation of scores over all partitions of a fixed size. We show that our test statistics based on summation can serve as good estimators of the mutual information. Moreover, we suggest regularized tests that aggregate over all partition sizes, and prove those are consistent too. We provide polynomial-time algorithms, which are critical for computing the suggested test statistics efficiently. We show that the power of the regularized tests is excellent compared to existing tests, and almost as powerful as the tests based on the optimal (yet unknown in practice) partition size, in simulations as well as on a real data example.

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arXiv2014

Consistent distribution-free tests of association between univariate random variables

We consider the problem of testing whether pairs of univariate random variables are associated. Few tests of independence exist that are consistent against all dependent alternatives and are distribution free. We propose novel tests that are consistent, distribution free, and have excellent power properties. The tests have simple form, and are surprisingly computationally efficient thanks to accompanying innovative algorithms we develop. Moreover, we show that one of the test statistics is a consistent estimator of the mutual information. We demonstrate the good power properties in simulations, and apply the tests to a microarray study where many pairs of genes are examined simultaneously for co-dependence.

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arXiv2014

A Quantile Regression Model for Failure-Time Data with Time-Dependent Covariates

Since survival data occur over time, often important covariates that we wish to consider also change over time. Such covariates are referred as time-dependent covariates. Quantile regression offers flexible modeling of survival data by allowing the covariates to vary with quantiles. This paper provides a novel quantile regression model accommodating time-dependent covariates, for analyzing survival data subject to right censoring. Our simple estimation technique assumes the existence of instrumental variables. In addition, we present a doubly-robust estimator in the sense of Robins and Rotnitzky (1992). The asymptotic properties of the estimators are rigorously studied. Finite-sample properties are demonstrated by a simulation study. The utility of the proposed methodology is demonstrated using the Stanford heart transplant dataset.

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arXiv2012

A consistent multivariate test of association based on ranks of distances

We are concerned with the detection of associations between random vectors of any dimension. Few tests of independence exist that are consistent against all dependent alternatives. We propose a powerful test that is applicable in all dimensions and is consistent against all alternatives. The test has a simple form and is easy to implement. We demonstrate its good power properties in simulations and on examples.

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arXiv2007

Case-Control Survival Analysis with a General Semiparametric Shared Frailty Model - a Pseudo Full Likelihood Approach

In this work we deal with correlated failure time (age at onset) data arising from population-based case-control studies, where case and control probands are selected by population-based sampling and an array of risk factor measures is collected for both cases and controls and their relatives. Parameters of interest are effects of risk factors on the hazard function of failure times and within-family dependencies of failure times after adjusting for the risk factors. Due to the retrospective nature of sampling, a large sample theory for existing methods has not been established. We develop a novel estimation techniques for estimating these parameters under a general semiparametric shared frailty model. We also present a simple, easily computed, and non-iterative nonparametric estimator for the cumulative baseline hazard function. A rigorous large sample theory for the proposed estimators of these parameters is given along with simulations and a real data example illustrate the utility of the proposed method.

math.ST↗

arXiv2006

Pseudo full likelihood estimation for prospective survival analysis with a general semiparametric shared frailty model: asymptotic theory

In this work we present a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Earlier work showed this method to perform well in a simulation study. Here we provide rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter, including consistent variance estimators.

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arXiv2005

Prospective survival analysis with a general semiparametric shared frailty model - a pseudo full likelihood approach

In this work we provide a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter is given, including consistent variance estimators. In a simulation study under the widely used gamma frailty model, our proposed approach was found to have essentially the same efficiency as the EM-based estimator considered by other authors, with negligible difference between the standard errors of the two estimators. The proposed approach, however, provides a framework capable of handling general frailty distributions with finite moments and yields an explicit consistent variance estimator.

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