Variance estimation of DEE and regression estimator when a first-phase cluster sample is restratified

We consider a variance estimation when a stratified single stage cluster sample is selected in the first phase and a stratified simple random element sample is selected in the second phase. We propose explicit formulas of (asymptotically), we propose explicit formulas of (asymptotically) unbiased variance estimators for the double expansion estimator and regression estimator. We perform a small simulation study to investigate the performance of the proposed variance estimators. In our simulation study, the proposed variance estimator showed better or comparable performance to the Jackknife variance estimator. We also extend the results to a two-phase sampling design in which a stratified pps with replacement cluster sample is selected in the first phase.     

Sample size determination for clustered right-censored data using copula models

Determination of an adequate sample size is critical to the design of research ventures. For clustered right-censored data, Manatunga and Chen [Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes. Biometrics. 2000;56(2):616–621] proposed a sample size calculation based on considering the bivariate marginal distribution as Clayton copula model. In addition to the Clayton copula, other important family of copulas, such as Gumbel and Frank copulas are also well established in multivariate survival analysis. However, sample size calculation based on these assumptions has not been fully investigated yet. To broaden the scope of Manatunga and Chen [Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes. Biometrics. 2000;56(2):616–621]'s research and achieve a more flexible sample size calculation for clustered right-censored data, we extended the work by assuming the marginal distribution as bivariate Gumbel and Frank copulas. We evaluate the performance of the proposed method and investigate the impacts of the accrual times, follow-up times and the within-clustered correlation effect of the study. The proposed method is applied to two real-world studies, and the R code is made available to users.     

Unbalanced cluster sizes and rates of convergence in mixed-effects models for clustered data

ABSTRACT

Convergence problems often arise when complex linear mixed-effects models are fitted. Previous simulation studies (see, e.g. [Buyse M, Molenberghs G, Burzykowski T, Renard D, Geys H. The validation of surrogate endpoints in meta-analyses of randomized experiments. Biostatistics. 2000;1:49–67, Renard D, Geys H, Molenberghs G, Burzykowski T, Buyse M. Validation of surrogate endpoints in multiple randomized clinical trials with discrete outcomes. Biom J. 2002;44:921–935]) have shown that model convergence rates were higher (i) when the number of available clusters in the data increased, and (ii) when the size of the between-cluster variability increased (relative to the size of the residual variability). The aim of the present simulation study is to further extend these findings by examining the effect of an additional factor that is hypothesized to affect model convergence, i.e. imbalance in cluster size. The results showed that divergence rates were substantially higher for data sets with unbalanced cluster sizes – in particular when the model at hand had a complex hierarchical structure. Furthermore, the use of multiple imputation to restore ‘balance’ in unbalanced data sets reduces model convergence problems.     

Regression analysis of clustered interval-censored failure time data with linear transformation models in the presence of informative cluster size

This paper discusses regression analysis of clustered interval-censored failure time data, which often occur in medical follow-up studies among other areas. For such data, sometimes the failure time may be related to the cluster size, the number of subjects within each cluster or we have informative cluster sizes. For the problem, we present a within-cluster resampling method for the situation where the failure time of interest can be described by a class of linear transformation models. In addition to the establishment of the asymptotic properties of the proposed estimators of regression parameters, an extensive simulation study is conducted for the assessment of the finite sample properties of the proposed method and suggests that it works well in practical situations. An application to the example that motivated this study is also provided.     

Profile likelihood approaches for semiparametric copula and frailty models for clustered survival data

ABSTRACT

In clustered survival data, the dependence among individual survival times within a cluster has usually been described using copula models and frailty models. In this paper we propose a profile likelihood approach for semiparametric copula models with different cluster sizes. We also propose a likelihood ratio method based on profile likelihood for testing the absence of association parameter (i.e. test of independence) under the copula models, leading to the boundary problem of the parameter space. For this purpose, we show via simulation study that the proposed likelihood ratio method using an asymptotic chi-square mixture distribution performs well as sample size increases. We compare the behaviors of the two models using the profile likelihood approach under a semiparametric setting. The proposed method is demonstrated using two well-known data sets.     

Unbiased estimators for restricted adaptive cluster sampling

In adaptive cluster sampling the size of the final sample is random, thus creating design problems. To get round this, Brown (1994) and Brown & Manly (1998) proposed a modification of the method, placing a restriction on the size of the sample, and using standard but biased estimators for estimating the population mean. But in this paper a new unbiased estimator and an unbiased variance estimator are proposed, based on estimators proposed by Murthy (1957) and extended to sequential and adaptive sampling designs by Salehi & Seber (2001). The paper also considers a restricted version of the adaptive scheme of Salehi & Seber (1997a) in which the networks are selected without replacement, and obtains unbiased estimators. The method is demonstrated by a simple example. Using simulation from this example, the new estimators are shown to compare very favourably with the standard biased estimators.     

Power and sample size for GEE analysis of incomplete paired outcomes in 2 × 2 crossover trials

The 2 × 2 crossover trial uses subjects as their own control to reduce the intersubject variability in the treatment comparison, and typically requires fewer subjects than a parallel design. The generalized estimating equations (GEE) methodology has been commonly used to analyze incomplete discrete outcomes from crossover trials. We propose a unified approach to the power and sample size determination for the Wald Z-test and t-test from GEE analysis of paired binary, ordinal and count outcomes in crossover trials. The proposed method allows misspecification of the variance and correlation of the outcomes, missing outcomes, and adjustment for the period effect. We demonstrate that misspecification of the working variance and correlation functions leads to no or minimal efficiency loss in GEE analysis of paired outcomes. In general, GEE requires the assumption of missing completely at random. For bivariate binary outcomes, we show by simulation that the GEE estimate is asymptotically unbiased or only minimally biased, and the proposed sample size method is suitable under missing at random (MAR) if the working correlation is correctly specified. The performance of the proposed method is illustrated with several numerical examples. Adaption of the method to other paired outcomes is discussed.     

Testing of mean interval for interval-valued data

Abstract

A new parametric hypothesis test of mean interval for interval-valued data set, which can deal with massive information contained in nowadays massive data “Big data” sets, is proposed. An approach using an orthogonal transformation is introduced to obtain an equivalent hypothesis test of mean interval in terms of the mid-point and mid-range of the interval-valued variable. The new test is very efficient in small interval-valued sample scenarios. Some simulation studies are conducted for the investigation of the sample size and the power of test. The performance of the proposed test is illustrated with two real-life examples.     

Sample size determination for cluster randomization phase II trials of dichotomous data

One of the main goals for a phase II trial is to screen and select the best treatment to proceed onto further studies in a phase III trial. Under the flexible design proposed elsewhere, we discuss for cluster randomization trials sample size calculation with a given desired probability of correct selection to choose the best treatment when one treatment is better than all the others. We develop exact procedures for calculating the minimum required number of clusters with a given cluster size (or the minimum number of patients with a given number of repeated measurements) per treatment. An approximate sample size and the evaluation of its performance for two arms are also given. To help readers employ the results presented here, tables are provided to summarize the resulting minimum required sample sizes for cluster randomization trials with two arms and three arms in a variety of situations. Finally, to illustrate the sample size calculation procedures developed here, we use the data taken from a cluster randomization trial to study the association between the dietary sodium and the blood pressure.     

Power of the adjusted Q statistic to evaluate heterogeneity in meta-analyses of cluster randomized trials

Because of its simplicity, the Q statistic is frequently used to test the heterogeneity of the estimated intervention effect in meta-analyses of individually randomized trials. However, it is inappropriate to apply it directly to the meta-analyses of cluster randomized trials without taking clustering effects into account. We consider the properties of the adjusted Q statistic for testing heterogeneity in the meta-analyses of cluster randomized trials with binary outcomes. We also derive an analytic expression for the power of this statistic to detect heterogeneity in meta-analyses, which can be useful when planning a meta-analysis. A simulation study is used to assess the performance of the adjusted Q statistic, in terms of its Type I error rate and power. The simulation results are compared to that obtained from the proposed formula. It is found that the adjusted Q statistic has a Type I error rate close to the nominal level of 5%, as compared to the unadjusted Q statistic commonly used to test for heterogeneity in the meta-analyses of individually randomized trials with an inflated Type I error rate. Data from a meta-analysis of four cluster randomized trials are used to illustrate the procedures.     

The LAD estimation of the change-point linear model with randomly censored data

Abstract

In this paper, a change-point linear model with randomly censored data is investigated. We propose the least absolute deviation estimation procedure for regression and change-point parameters simultaneously. The asymptotic properties of the change-point and regression parameter estimators are obtained. We show that the resulting regression parameter estimator is asymptotically normal, and the change-point estimator converges weakly to the minimizer of a given random process. The extensive simulation studies and the analysis of an acute myocardial infarction data set are conducted to illustrate the finite sample performance of the proposed method.     

Testing for center effects on survival and competing risks outcomes using pseudo-value regression

In multi-center studies, the presence of a cluster effect leads to correlation among outcomes within a center and requires different techniques to handle such correlation. Testing for a cluster effect can serve as a pre-screening step to help guide the researcher towards the appropriate analysis. With time to event data, score tests have been proposed which test for the presence of a center effect on the hazard function. However, sometimes researchers are interested in directly modeling other quantities such as survival probabilities or cumulative incidence at a fixed time. We propose a test for the presence of a center effect acting directly on the quantity of interest using pseudo-value regression, and derive the asymptotic properties of our proposed test statistic. We examine the performance of our proposed test through simulation studies in both survival and competing risks settings. The proposed test may be more powerful than tests based on the hazard function in settings where the center effect is time-varying. We illustrate the test using a multicenter registry study of survival and competing risks outcomes after hematopoietic cell transplantation.

     

Proportional Trapping-Removal Model with a Known Ratio

ABSTRACT

Population size estimator is derived for a proportional trapping-removal model with a known ratio between two sub-population sizes, and the corresponding asymptotic properties is obtained. The performance of the proposed estimator is checked via simulation studies and an example.     

Bias Reduction in Logistic Regression with Missing Responses When the Missing Data Mechanism is Nonignorable

ABSTRACT

In logistic regression with nonignorable missing responses, Ibrahim and Lipsitz proposed a method for estimating regression parameters. It is known that the regression estimates obtained by using this method are biased when the sample size is small. Also, another complexity arises when the iterative estimation process encounters separation in estimating regression coefficients. In this article, we propose a method to improve the estimation of regression coefficients. In our likelihood-based method, we penalize the likelihood by multiplying it by a noninformative Jeffreys prior as a penalty term. The proposed method reduces bias and is able to handle the issue of separation. Simulation results show substantial bias reduction for the proposed method as compared to the existing method. Analyses using real world data also support the simulation findings. An R package called brlrmr is developed implementing the proposed method and the Ibrahim and Lipsitz method.     

Generation of pseudo random numbers and estimation under Cox models with time-dependent covariates

ABSTRACT

We study the method for generating pseudo random numbers under various special cases of the Cox model with time-dependent covariates when the baseline hazard function may not be constant and the random variable may equal infinity with a positive probability. During our simulation studies in computing the partial likelihood estimates, in between 3% and 20% of the time with a moderate sample size, it happens that the partial likelihood estimate of the regression coefficient is ∞ for the data from the Cox model. We propose a semi-parametric estimator as a modification for such a case. We present simulation results on the asymptotic properties of the semi-parametric estimator.     

Statistical inference for the accelerated failure time model under two-stage generalized case–cohort design

Abstract

In this article, we propose a two-stage generalized case–cohort design and develop an efficient inference procedure for the data collected with this design. In the first-stage, we observe the failure time, censoring indicator and covariates which are easy or cheap to measure, and in the second-stage, select a subcohort by simple random sampling and a subset of failures in remaining subjects from the first-stage subjects to observe their exposures which are different or expensive to measure. We derive estimators for regression parameters in the accelerated failure time model under the two-stage generalized case–cohort design through the estimated augmented estimating equation and the kernel function method. The resulting estimators are shown to be consistent and asymptotically normal. The finite sample performance of the proposed method is evaluated through the simulation studies. The proposed method is applied to a real data set from the National Wilm’s Tumor Study Group.     

M-Estimation for partially functional linear regression model based on splines

ABSTRACT

M-estimation is a widely used technique for robust statistical inference. In this paper, we study robust partially functional linear regression model in which a scale response variable is explained by a function-valued variable and a finite number of real-valued variables. For the estimation of the regression parameters, which include the infinite dimensional function as well as the slope parameters for the real-valued variables, we use polynomial splines to approximate the slop parameter. The estimation procedure is easy to implement, and it is resistant to heavy-tailederrors or outliers in the response. The asymptotic properties of the proposed estimators are established. Finally, we assess the finite sample performance of the proposed method by Monte Carlo simulation studies.     

A spatial scan statistic for survival data based on generalized life distribution

ABSTRACT

For many years, detection of clusters has been of great public health interest and widely studied. Several methods have been developed to detect clusters and their performance has been evaluated in various contexts. Spatial scan statistics are widely used for geographical cluster detection and inference. Different types of discrete or continuous data can be analyzed using spatial scan statistics for Bernoulli, Poisson, ordinal, exponential, and normal models. In this paper, we propose a scan statistic for survival data which is based on generalized life distribution model that provides three important life distributions, viz. Weibull, exponential, and Rayleigh. The proposed method is applied to the survival data of tuberculosis patients in Nainital district of Uttarakhand, India, for the year 2004–05. The Monte Carlo simulation studies reveal that the proposed method performs well for different survival distributions.