On Goodness-of-Fit Tests for Aalen's Additive Risk Model

Abstract.  In this paper we propose goodness-of-fit tests for Aalen's additive risk model. They are based on test statistics the asymptotic distributions of which are determined under both the null and alternative hypotheses. The results are derived using martingale techniques for counting processes. An important feature of these tests is that they can be adjusted to particular alternatives. One of the alternatives we consider is Cox's multiplicative risk model. It is perhaps remarkable that such a test needs no estimate of the baseline hazard in the Cox model. We present simulation studies which give an impression of the performance of the proposed tests. In addition, the tests are applied to real data sets.     

Checking a Semiparametric Additive Risk Model

McKeague and Sasieni [A partly parametric additive risk model. Biometrika 81 (1994) 501] propose a restriction of Aalen’s additive risk model by the additional hypothesis that some of the covariates have time-independent influence on the intensity of the observed counting process. We introduce goodness-of-fit tests for this semiparametric Aalen model. The asymptotic distribution properties of the test statistics are derived by means of martingale techniques. The tests can be adjusted to detect particular alternatives. As one of the most important alternatives we consider Cox’s proportional hazards model. We present simulation studies and an application to a real data set.     

Additive transformation models for clustered failure time data

We propose a class of additive transformation risk models for clustered failure time data. Our models are motivated by the usual additive risk model for independent failure times incorporating a frailty with mean one and constant variability which is a natural generalization of the additive risk model from univariate failure time to multivariate failure time. An estimating equation approach based on the marginal hazards function is proposed. Under the assumption that cluster sizes are completely random, we show the resulting estimators of the regression coefficients are consistent and asymptotically normal. We also provide goodness-of-fit test statistics for choosing the transformation. Simulation studies and real data analysis are conducted to examine the finite-sample performance of our estimators.     

Additive mixed effect model for recurrent gap time data

Gap times between recurrent events are often of primary interest in medical and observational studies. The additive hazards model, focusing on risk differences rather than risk ratios, has been widely used in practice. However, the marginal additive hazards model does not take the dependence among gap times into account. In this paper, we propose an additive mixed effect model to analyze gap time data, and the proposed model includes a subject-specific random effect to account for the dependence among the gap times. Estimating equation approaches are developed for parameter estimation, and the asymptotic properties of the resulting estimators are established. In addition, some graphical and numerical procedures are presented for model checking. The finite sample behavior of the proposed methods is evaluated through simulation studies, and an application to a data set from a clinic study on chronic granulomatous disease is provided.     

Non‐parametric Maximum Likelihood Estimation for Cox Regression with Subject‐Specific Measurement Error

Abstract. Many epidemiological studies have been conducted to identify an association between nutrient consumption and chronic disease risk. To this problem, Cox regression with additive covariate measurement error has been well developed in the literature. However, researchers are concerned with the validity of the additive measurement error assumption for self‐report nutrient data. Recently, some study designs using more reliable biomarker data have been considered, in which the additive measurement error assumption is more likely to hold. Biomarker data are often available in a subcohort. Self‐report data often encounter with a variety of serious biases. Complications arise primarily because the magnitude of measurement errors is often associated with some characteristics of a study subject. A more general measurement error model has been developed for self‐report data. In this paper, a non‐parametric maximum likelihood (NPML) estimator using an EM algorithm is proposed to simultaneously adjust for the general measurement errors.     

Goodness-of-fit tests in semi-linear models

Specification tests for the error distribution are proposed in semi-linear models, including the partial linear model and additive models. The tests utilize an integrated distance involving the empirical characteristic function of properly estimated residuals. These residuals are obtained from an initial estimation step involving a combination of penalized least squares and smoothing techniques. A bootstrap version of the tests is utilized in order to study the small sample behavior of the procedures in comparison with more classical approaches. As an example, the tests are applied on some real data sets.     

Goodness-of-fit tests for additive mean residual life model under right censoring

The mean residual life (MRL) measures the remaining life expectancy and is useful in actuarial studies, biological experiments and clinical trials. To assess the covariate effect, an additive MRL regression model has been proposed in the literature. In this paper, we focus on the topic of model checking. Specifically, we develop two goodness-of-fit tests to test the additive MRL model assumption. We explore the large sample properties of the test statistics and show that both of them are based on asymptotic Gaussian processes so that resampling approaches can be applied to find the rejection regions. Simulation studies indicate that our methods work reasonably well for sample sizes ranging from 50 to 200. Two empirical data sets are analyzed to illustrate the approaches.     

Generalized likelihood ratio tests for the structure of semiparametric additive models

Semiparametric additive models (SAMs) are very useful in multivariate nonparametric regression. In this paper, the authors study nonparametric testing problems for the nonparametric components of SAMs. Using the backfitting algorithm and the local polynomial smoothing technique, they extend to SAMs the generalized likelihood ratio tests of Fan &Jiang (2005). The authors show that the proposed tests possess the Wilks‐type property and that they can detect alternatives nearing the null hypothesis with a rate arbitrarily close to root‐n while error distributions are unspecified. They report simulations which demonstrate the Wilks phenomenon and the powers of their tests. They illustrate the performance of their approach by simulation and using the Boston housing data set.     

Testing for additivity and joint effects in multivariate nonparametric regression using Fourier and wavelet methods

We consider the problem of testing for additivity and joint effects in multivariate nonparametric regression when the data are modelled as observations of an unknown response function observed on a d-dimensional (d 2) lattice and contaminated with additive Gaussian noise. We propose tests for additivity and joint effects, appropriate for both homogeneous and inhomogeneous response functions, using the particular structure of the data expanded in tensor product Fourier or wavelet bases studied recently by Amato and Antoniadis (2001) and Amato, Antoniadis and De Feis (2002). The corresponding tests are constructed by applying the adaptive Neyman truncation and wavelet thresholding procedures of Fan (1996), for testing a high-dimensional Gaussian mean, to the resulting empirical Fourier and wavelet coefficients. As a consequence, asymptotic normality of the proposed test statistics under the null hypothesis and lower bounds of the corresponding powers under a specific alternative are derived. We use several simulated examples to illustrate the performance of the proposed tests, and we make comparisons with other tests available in the literature.     

An Additive Genetic Gamma Frailty Model for Linkage Analysis of Diseases with Variable Age of Onset Using Nuclear Families

Many late-onset complex diseases exhibit variable age of onset. Efficiently incorporating age of onset information into linkage analysis can potentially increase the power of dissecting complex diseases. In this paper, we treat age of onset as a genetic trait with censored observations. We use multiple markers to infer the inheritance vector at the disease susceptibility (DS) locus in order to extract information about the inheritance pattern of the disease allele in a pedigree. Given the inheritance distribution at the DS locus, we define the genetic frailty for each individual within a nuclear family as the sum of frailties due to a putative major disease gene and a polygenic effect due to any remaining DS loci. Conditioning on these frailties we use the proportional hazards model for the risk of developing disease. We show that a test of linkage can be formulated as a test of zero variance due to a specific locus of the additive gamma frailties. Maximum likelihood estimation, using the EM algorithm, and likelihood ratio tests are employed for parameter estimation and tests of linkage. A simulation study presented indicates that the proposed method is well behaved and can be more powerful than the currently available allele-sharing based linkage methods. A breast cancer data example is used for illustration.     

Testing linearity against nonlinear moving average models

Lagrange multiplier (LM) test statistics are derived for testing a linear moving average model against an asymmetric moving average model and an LM type test against an additive smooth transition moving average model. The latter model is introduced in the paper. The small sample performance of the proposed tests are evaluated in a Monte Carlo study and compared to Wald and likelihood ratio statistics. The size properties of the Lagrange multiplier test are better than those of other tests.     

Semiparametric additive marginal regression models for multiple type recurrent events

Recurrent event data are often encountered in biomedical research, for example, recurrent infections or recurrent hospitalizations for patients after renal transplant. In many studies, there are more than one type of events of interest. Cai and Schaube (Lifetime Data Anal 10:121-138, 2004) advocated a proportional marginal rate model for multiple type recurrent event data. In this paper, we propose a general additive marginal rate regression model. Estimating equations approach is used to obtain the estimators of regression coefficients and baseline rate function. We prove the consistency and asymptotic normality of the proposed estimators. The finite sample properties of our estimators are demonstrated by simulations. The proposed methods are applied to the India renal transplant study to examine risk factors for bacterial, fungal and viral infections.     

Permutation tests for between-unit fixed effects in multivariate generalized linear mixed models

A permutation testing approach in multivariate mixed models is presented. The solutions proposed allow for testing between-unit effect; they are exact under some assumptions, while approximated in the more general case. The classes of models comprised by this approach include generalized linear models, vector generalized additive models and other nonparametric models based on smoothing. Moreover it does not assume observations of different units to have the same distribution. The extensions to a multivariate framework are presented and discussed. The proposed multivariate tests exploit the dependence among variables, hence increasing the power with respect to other standard solutions (e.g. Bonferroni correction) which combine many univariate tests in an overall one. Examples are given of two applications to real data from psychological and ecological studies; a simulation study provides some insight into the unbiasedness of the tests and their power. The methods were implemented in the R package flip, freely available on CRAN.     

SiZer Map for inference with additive models

Sizer Map is proposed as a graphical tool for assistance in nonparametric additive regression testing problems. Four problems have been analyzed by using SiZer Map: testing for additivity, testing the components significance, testing parametric models for the components and testing for interactions. The simplicity and flexibility of SiZer Map for our purposes are highlighted from the performed empirical study with several real datasets. With these data, we compare the conclusions derived from SiZer analysis with the global results derived from standard tests, previously proposed in the literature.     

On goodness-of-fit tests for Aalen's additive model based on left-truncated right-censored or doubly censored data

ABSTRACT

Gandy and Jensen (2005 Gandy, A., Jensen, U. (2005). On goodness-of-fit tests for Aalen's additive risk model. Scan. J. Stat. 32:425–445.[Crossref], [Web of Science ®] , [Google Scholar]) proposed goodness-of-fit tests for Aalen's additive risk model. In this article, we demonstrate that the approach of Gandy and Jensen (2005 Gandy, A., Jensen, U. (2005). On goodness-of-fit tests for Aalen's additive risk model. Scan. J. Stat. 32:425–445.[Crossref], [Web of Science ®] , [Google Scholar]) can be applied to left-truncated right-censored (LTRC) data and doubly censored data. A simulation study is conducted to investigate the performance of the proposed tests. The proposed tests are illustrated using heart transplant data.     

Tests for comparison of competing risks under the additive risk model

It is of interest that researchers study competing risks in which subjects may fail from any one of k causes. Comparing any two competing risks with covariate effects is very important in medical studies. In this paper, we develop tests for comparing cause-specific hazard rates and cumulative incidence functions at specified covariate levels under the additive risk model by a weighted difference of estimates of cumulative cause-specific hazard rates. Motivated by McKeague et al. (2001), we construct simultaneous confidence bands for the difference of two conditional cumulative incidence functions as a useful graphical tool. In addition, we conduct a simulation study, and the simulation result shows that the proposed procedure has a good finite sample performance. A melanoma data set in clinical trial is used for the purpose of illustration.     

Mark-specific additive hazards regression with continuous marks

For survival data, mark variables are only observed at uncensored failure times, and it is of interest to investigate whether there is any relationship between the failure time and the mark variable. The additive hazards model, focusing on hazard differences rather than hazard ratios, has been widely used in practice. In this article, we propose a mark-specific additive hazards model in which both the regression coefficient functions and the baseline hazard function depend nonparametrically on a continuous mark. An estimating equation approach is developed to estimate the regression functions, and the asymptotic properties of the resulting estimators are established. In addition, some formal hypothesis tests are constructed for various hypotheses concerning the mark-specific treatment effects. The finite sample behavior of the proposed estimators is evaluated through simulation studies, and an application to a data set from the first HIV vaccine efficacy trial is provided.     

Testing equality of cause-specific hazard rates corresponding to m competing risks among K groups

In this paper, a class of tests is developed for comparing the cause-specific hazard rates of m competing risks simultaneously in K ( 2) groups. The data available for a unit are the failure time of the unit along with the identifier of the risk claiming the failure. In practice, the failure time data are generally right censored. The tests are based on the difference between the weighted averages of the cause-specific hazard rates corresponding to each risk. No assumption regarding the dependence of the competing risks is made. It is shown that the proposed test statistic has asymptotically chi-squared distribution. The proposed test is shown to be optimal for a specific type of local alternatives. The choice of weight function is also discussed. A simulation study is carried out using multivariate Gumbel distribution to compare the optimal weight function with a proposed weight function which is to be used in practice. Also, the proposed test is applied to real data on the termination of an intrauterine device.An erratum to this article can be found at     

An additive Cox model for coronary heart disease study

Existing models for coronary heart disease study use a set of common risk factors to predict the survival time of the disease, via the standard Cox regression model. For complex relationships between the survival time and risk factors, the linear regression specification in the existing Cox model is not flexible enough to accounts for such relationships. Also, the risk factors are actually risky only when they fall in some risk ranges. For more flexibility in modelling and characterize the risk factors more accurately, we study a semi-parametric additive Cox model, using basis splines and LASSO technique. The proposed model is evaluated by simulation studies and is used for the analysis of a real data in the Strong Heart Study.     

Testing the homogeneity of risk differences with sparse count data

ABSTRACT

In this paper, we consider testing the homogeneity of risk differences in independent binomial distributions especially when data are sparse. We point out some drawback of existing tests in either controlling a nominal size or obtaining powers through theoretical and numerical studies. The proposed test is designed to avoid the drawbacks of existing tests. We present the asymptotic null distribution and asymptotic power function for the proposed test. We also provide numerical studies including simulations and real data examples showing the proposed test has reliable results compared to existing testing procedures.