A comparison of linear regression techniques in method comparison studies

In this study, the performances of linear regression techniques, which are especially used in clinical chemistry in method comparison studies, are compared via the Monte-Carlo simulation. The regression techniques that take the measurement errors of both dependent and independent variables into account are called Type II regression techniques. In this study, we also compare the performances of Type II and Type I (classical regression techniques that do not take the measurement errors of the independent variable into account) regression techniques for different sample sizes and different shape parameters of the Weibull distribution. The mean square error is used as a performance criterion of each technique. MATLAB 7.02 software is used in the simulation study. As a result, in all conditions, the ordinary least-square (OLS)-bisector regression technique, which bisects the OLS(Y | X) and the OLS(X | Y), shows the best performance.     

SIMEX method for censored quantile regression with measurement error

Censored quantile regression serves as an important supplement to the Cox proportional hazards model in survival analysis. In addition to being exposed to censoring, some covariates may subject to measurement error. This leads to substantially biased estimate without taking this error into account. The SIMulation-EXtrapolation (SIMEX) method is an effective tool to handle the measurement error issue. We extend the SIMEX approach to the censored quantile regression with covariate measurement error. The algorithm is assessed via extensive simulations. A lung cancer study is analyzed to verify the validation of the proposed method.     

Sample size calculation based on risk ratio under multiple matching

To increase the efficiency of comparisons between treatments in clinical trials, we may consider the use of a multiple matching design, in which, for each patient receiving the experimental treatment, we match with more than one patient receiving the standard treatment. To assess the efficacy of the experimental treatment, the risk ratio (RR) of patient responses between two treatments is certainly one of the most commonly used measures. Because the probability of patient responses in clinical trial is often not small, the odds ratio (OR), of which the practical interpretation is not easily understood, cannot approximate RR well. Thus, all sample size formulae in terms of OR for case-control studies with multiple matched controls per case can be of limited use here. In this paper, we develop three sample size formulae based on RR for randomized trials with multiple matching. We propose a test statistic for testing the equality of RR under multiple matching. On the basis of Monte Carlo simulation, we evaluate the performance of the proposed test statistic with respect to Type I error. To evaluate the accuracy and usefulness of the three sample size formulae developed in this paper, we further calculate their simulated powers and compare them with those of the sample size formula ignoring matching and the sample size formula based on OR for multiple matching published elsewhere. Finally, we include an example that employs the multiple matching study design about the use of the supplemental ascorbate in the supportive treatment of terminal cancer patients to illustrate the use of these formulae.     

A risk set calibration method for failure time regression by using a covariate reliability sample

Regression parameter estimation in the Cox failure time model is considered when regression variables are subject to measurement error. Assuming that repeat regression vector measurements adhere to a classical measurement model, we can consider an ordinary regression calibration approach in which the unobserved covariates are replaced by an estimate of their conditional expectation given available covariate measurements. However, since the rate of withdrawal from the risk set across the time axis, due to failure or censoring, will typically depend on covariates, we may improve the regression parameter estimator by recalibrating within each risk set. The asymptotic and small sample properties of such a risk set regression calibration estimator are studied. A simple estimator based on a least squares calibration in each risk set appears able to eliminate much of the bias that attends the ordinary regression calibration estimator under extreme measurement error circumstances. Corresponding asymptotic distribution theory is developed, small sample properties are studied using computer simulations and an illustration is provided.     

Sample sizes for trials involving multiple correlated must-win comparisons

In Clinical trials involving multiple comparisons of interest, the importance of controlling the trial Type I error is well-understood and well-documented. Moreover, when these comparisons are themselves correlated, methodologies exist for accounting for the correlation in the trial design, when calculating the trial significance levels. However, less well-documented is the fact that there are some circumstances where multiple comparisons affect the Type II error rather than the Type I error, and failure to account for this, can result in a reduction in the overall trial power. In this paper, we describe sample size calculations for clinical trials involving multiple correlated comparisons, where all the comparisons must be statistically significant for the trial to provide evidence of effect, and show how such calculations have to account for multiplicity in the Type II error. For the situation of two comparisons, we provide a result which assumes a bivariate Normal distribution. For the general case of two or more comparisons we provide a solution using inflation factors to increase the sample size relative to the case of a single outcome. We begin with a simple case of two comparisons assuming a bivariate Normal distribution, show how to factor in correlation between comparisons and then generalise our findings to situations with two or more comparisons. These methods are easy to apply, and we demonstrate how accounting for the multiplicity in the Type II error leads, at most, to modest increases in the sample size.     

Sample size calculation for testing non-inferiority and equivalence under Poisson distribution

When counting the number of chemical parts in air pollution studies or when comparing the occurrence of congenital malformations between a uranium mining town and a control population, we often assume Poisson distribution for the number of these rare events. Some discussions on sample size calculation under Poisson model appear elsewhere, but all these focus on the case of testing equality rather than testing equivalence. We discuss sample size and power calculation on the basis of exact distribution under Poisson models for testing non-inferiority and equivalence with respect to the mean incidence rate ratio. On the basis of large sample theory, we further develop an approximate sample size calculation formula using the normal approximation of a proposed test statistic for testing non-inferiority and an approximate power calculation formula for testing equivalence. We find that using these approximation formulae tends to produce an underestimate of the minimum required sample size calculated from using the exact test procedure. On the other hand, we find that the power corresponding to the approximate sample sizes can be actually accurate (with respect to Type I error and power) when we apply the asymptotic test procedure based on the normal distribution. We tabulate in a variety of situations the minimum mean incidence needed in the standard (or the control) population, that can easily be employed to calculate the minimum required sample size from each comparison group for testing non-inferiority and equivalence between two Poisson populations.     

On the relationship between the sample size and the number of variables in a linear regression model

The problem of determining the number of variables to be included in the linear regression model is considered under the assumption that the dependent and independent variables have a joint normal distribution. It is shown that for a given sample size n there exists an optimal number k₀ (0 ≤ k₀ < n-2) of variables among all independent variables in the model, such that the expectation of the mean squared error corresponding to the prediction equation with k₀ variables is minimal.Application of this result to ustepwise procedures is discussed.     

Sample size calculation for an agreement study

It is often necessary to compare two measurement methods in medicine and other experimental sciences. This problem covers a broad range of data. Many authors have explored ways of assessing the agreement of two sets of measurements. However, there has been relatively little attention to the problem of determining sample size for designing an agreement study. In this paper, a method using the interval approach for concordance is proposed to calculate sample size in conducting an agreement study. The philosophy behind this is that the concordance is satisfied when no more than the pre‐specified k discordances are found for a reasonable large sample size n since it is much easier to define a discordance pair. The goal here is to find such a reasonable large sample size n. The sample size calculation is based on two rates: the discordance rate and tolerance probability, which in turn can be used to quantify an agreement study. The proposed approach is demonstrated through a real data set. Copyright © 2009 John Wiley & Sons, Ltd.     

The optimal group size using inverse binomial group testing considering misclassification

ABSTRACT

Inverse binomial sampling is preferred for quick report. It is also recommended when the population proportion is really small to ensure a positive sample is contained. Group testing has been discussed extensively under binomial model, but not so much under negative binomial model. In this study, we investigate the problem of how to determine the group size using inverse binomial group testing. We propose to choose the optimal group size by minimizing asymptotic variance of the estimator or the cost relative to Fisher information. We show the good performance of our estimator by applying to the data of Chlamydia.     

Estimation in multiple linear regression Berkson model for processes with uncorrelated increments

This paper presents a method of estimating the regression and variance parameters in the multiple linear regression Berkson model for a continuous-time stochastic process with uncorrelated increments. Under minimal conditions, we establish (i) the Gauss–Markov theorem and the quadratic mean—as well as the strong consistency of the proposed estimate of the regression parameter and (ii) the weak consistency of the proposed estimate of the variance parameter.     

On preliminary test ridge regression estimators for linear restrictions in a regression model with non-normal disturbances

In this paper, we study the properties of the preliminary test, restricted and unrestricted ridge regression estimators of the linear regression model with non-normal disturbances. We present the estimators of the regression coefficients combining the idea of preliminary test and ridge regression methodology, when it is suspected that the regression coefficients may be restricted to a subspace and the regression error is distributed as multivariate t. Accordingly we consider three estimators, namely the Unrestricted Ridge Regression Estimator (URRRE), the Restricted Ridge Regression Estimator (RRRE) and finally the Preliminary test Ridge Regression Estimator (PTRRE). The biases and the mean square error (MSE) of the estimators are derived under the null and alternative hypotheses and compared with the usual estimators. By studying the MSE criterion, the regions of optimahty of the estimators are determined.     

Sample size recalculation for binary data in internal pilot study designs

For binary endpoints, the required sample size depends not only on the known values of significance level, power and clinically relevant difference but also on the overall event rate. However, the overall event rate may vary considerably between studies and, as a consequence, the assumptions made in the planning phase on this nuisance parameter are to a great extent uncertain. The internal pilot study design is an appealing strategy to deal with this problem. Here, the overall event probability is estimated during the ongoing trial based on the pooled data of both treatment groups and, if necessary, the sample size is adjusted accordingly. From a regulatory viewpoint, besides preserving blindness it is required that eventual consequences for the Type I error rate should be explained. We present analytical computations of the actual Type I error rate for the internal pilot study design with binary endpoints and compare them with the actual level of the chi‐square test for the fixed sample size design. A method is given that permits control of the specified significance level for the chi‐square test under blinded sample size recalculation. Furthermore, the properties of the procedure with respect to power and expected sample size are assessed. Throughout the paper, both the situation of equal sample size per group and unequal allocation ratio are considered. The method is illustrated with application to a clinical trial in depression. Copyright © 2004 John Wiley & Sons Ltd.     

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.     

Reducing errors-in-variables bias in linear regression using compact genetic algorithms

A new technique is devised to mitigate the errors-in-variables bias in linear regression. The procedure mimics a 2-stage least squares procedure where an auxiliary regression which generates a better behaved predictor variable is derived. The generated variable is then used as a substitute for the error-prone variable in the first-stage model. The performance of the algorithm is tested by simulation and regression analyses. Simulations suggest the algorithm efficiently captures the additive error term used to contaminate the artificial variables. Regressions provide further credit to the simulations as they clearly show that the compact genetic algorithm-based estimate of the true but unobserved regressor yields considerably better results. These conclusions are robust across different sample sizes and different variance structures imposed on both the measurement error and regression disturbances.     

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.     

Measure of location-based estimators in simple linear regression

In this note we consider certain measure of location-based estimators (MLBEs) for the slope parameter in a linear regression model with a single stochastic regressor. The median-unbiased MLBEs are interesting as they can be robust to heavy-tailed samples and, hence, preferable to the ordinary least squares estimator (LSE). Two different cases are considered as we investigate the statistical properties of the MLBEs. In the first case, the regressor and error is assumed to follow a symmetric stable distribution. In the second, other types of regressions, with potentially contaminated errors, are considered. For both cases the consistency and exact finite-sample distributions of the MLBEs are established. Some results for the corresponding limiting distributions are also provided. In addition, we illustrate how our results can be extended to include certain heteroskedastic and multiple regressions. Finite-sample properties of the MLBEs in comparison to the LSE are investigated in a simulation study.     

Statistical estimation for a partially linear single-index model with errors in all variables

This article considers partially linear single-index models with errors in all variables. By using the Pseudo ? θ method (Liang, Härdle, and Carroll 1999), local linear regression and simulation-extrapolation (SIMEX) technique (Cook and Stefanski 1994), we propose an efficient methodology to estimate the current model. Under certain conditions the asymptotic properties of proposed estimators are obtained. Some simulation experiments and an application are conducted to illustrate our proposed method.     

Detecting change in a hazard regression model with right-censoring

The hazard function plays an important role in survival analysis and reliability, since it quantifies the instantaneous failure rate of an individual at a given time point t, given that this individual has not failed before t. In some applications, abrupt changes in the hazard function are observed, and it is of interest to detect the location of such a change. In this paper, we consider testing of existence of a change in the parameters of an exponential regression model, based on a sample of right-censored survival times and the corresponding covariates. Likelihood ratio type tests are proposed and non-asymptotic bounds for the type II error probability are obtained. When the tests lead to acceptance of a change, estimators for the location of the change are proposed. Non-asymptotic upper bounds of the underestimation and overestimation probabilities are obtained. A short simulation study illustrates these results.     

Adaptive LASSO for linear regression models with ARMA-GARCH errors

The linear regression models with the autoregressive moving average (ARMA) errors (REGARMA models) are often considered, in order to reflect a serial correlation among observations. In this article, we focus on an adaptive least absolute shrinkage and selection operator (LASSO) (ALASSO) method for the variable selection of the REGARMA models and extend it to the linear regression models with the ARMA-generalized autoregressive conditional heteroskedasticity (ARMA-GARCH) errors (REGARMA-GARCH models). This attempt is an extension of the existing ALASSO method for the linear regression models with the AR errors (REGAR models) proposed by Wang et al. in 2007 Wang, H., Li, G., Tsai, C. (2007). Regression coefficient and autoregressive order shrinkage and selection via the lasso. Journal of the Royal Statistical Society: Series B 69:63–78. [Google Scholar]. New ALASSO algorithms are proposed to determine important predictors for the REGARMA and REGARMA-GARCH models. Finally, we provide the simulation results and real data analysis to illustrate our findings.     

Sample size determination for testing equality in frequency data under an incomplete block crossover design

When there are more than two treatments under comparison, we may consider the use of the incomplete block crossover design (IBCD) to save the number of patients needed for a parallel groups design and reduce the duration of a crossover trial. We develop an asymptotic procedure for simultaneously testing equality of two treatments versus a control treatment (or placebo) in frequency data under the IBCD with two periods. We derive a sample size calculation procedure for the desired power of detecting the given treatment effects at a nominal-level and suggest a simple ad hoc adjustment procedure to improve the accuracy of the sample size determination when the resulting minimum required number of patients is not large. We employ Monte Carlo simulation to evaluate the finite-sample performance of the proposed test, the accuracy of the sample size calculation procedure, and that with the simple ad hoc adjustment suggested here. We use the data taken as a part of a crossover trial comparing the number of exacerbations between using salbutamol or salmeterol and a placebo in asthma patients to illustrate the sample size calculation procedure.