Random norming aids analysis of non-linear regression models with sequential informative dose selection

Wiley-Interscience Paperback Series Wiley-Interscience Paperback Series consists of selected books that have been made more accessible to consumers in an effort to increase global appeal and general circulation. With these new unabridged softcover volumes, Wiley hopes to extend the lives of these works by making them available to future generations of statisticians, mathematicians, and scientists. The authors have put together an extraordinary presentation of concepts and methods concerning the use and analysis of nonlinear regression models ...highly recommend[ed] ...for anyone needing to use and/or understand issues concerning the analysis of nonlinear regression -Technometrics [This book] provides a good balance of relevant theory and application with many examples ...[and it] provides the most balanced approach to theory and application appropriate for a first course in nonlinear regression modeling for graduate statistics students. -Mathematical Reviews [This book] joins a distinguished list of publications with a reputation for balancing technical rigor with readability, and theory with application. [It] upholds tradition ...[and is] a worthwhile reference for the marketing researcher with a serious interest in linear models. -Journal of Marketing Research This book offers a balanced presentation of the theoretical, practical, and computational aspects of nonlinear regression and provides background material on linear regression, including the geometrical development for linear and nonlinear least squares. authors employ real data sets throughout, and their extensive use of geometric constructs and continuing examples makes the progression of ideas appear very natural. book also includes pseudocode for computing algorithms.

The paper outlines a method of analysis of intricically non‐linear regression functions. The nonlinear model is first approximated by a cubic spline function. Thereafter, the standard methods of analysis in linear models are applied to obtain estimates and test statistics.

Sample size calculations for gene expression microarray and NGS-RNA-Seq experiments are challenging because the overall power depends on unknown quantities as the proportion of true null hypotheses and the distribution of the effect sizes under the alternative. We propose a two-stage design with an adaptive interim analysis where these quantities are estimated from the interim data. The second stage sample size is chosen based on these estimates to achieve a specific overall power. The proposed procedure controls the power in all considered scenarios except for very low first stage sample sizes. The false discovery rate (FDR) is controlled despite of the data dependent choice of sample size. The two-stage design can be a useful tool to determine the sample size of high-dimensional studies if in the planning phase there is high uncertainty regarding the expected effect sizes and variability.

In this paper, heteroscedastic nonlinear regression (HNLR) models under the flexible class of two–piece distributions based on the scale mixtures of normal (TP–SMN) family were examined. This novel class of nonlinear regression (NLR) models is a generalization of the well-known heteroscedastic symmetrical nonlinear regression models. The TP–SMN is a rich class of distributions that covers symmetric and asymmetric as well as heavy-tailed distributions. Using the suitable hierarchical representation of the family, the researchers first derived an EM–type algorithm for iteratively computing maximum likelihood (ML) estimates of the parameters. Then, in order to examine the performance of the proposed models and methods, some simulation studies were presented to show the robust aspect of this flexible class against outlying and also atypical data. As the last step, a natural real dataset was fitted under the proposed HNLR models.

Questa nota intende dare alcuni criteri generali per costruire stime di parametri da funzioni curve cubiche. Tali funzioni sono particolarmente utili nell'analisi di modelli non lineari per le loro proprieta di convergenza (Ahlberg e altri, 1967). Illustra quindi l'effetto dei coefficienti di correlazione multipla sulle proprieta delle stime quando il modello lineare sottinteso e una funzione esponenziale a tre parametri. Esempi numerici sono gia stati pubblicati dall'Autore (1982, 1984).

The Maximum Likelihood (ML) and Best Linear Unbiased (BLU) estimators of the location and scale parameters of an extreme value distribution (Lawless [1982]) are compared under conditions of small sample sizes and Type I censorship. The comparisons were made in terms of the mean square error criterion. According to this criterion, the ML estimator of σ in the case of very small sample sizes (n < 10) and heavy censorship (low censoring time) proved to be more efficient than the corresponding BLU estimator. However, the BLU estimator for σ attains parity with the corresponding ML estimator when the censoring time increases even for sample sizes as low as 10. The BLU estimator of σ attains equivalence with the ML estimator when the sample size increases above 10, particularly when the censoring time is also increased. The situation is reversed when it came to estimating the location parameter μ, as the BLU estimator was found to be consistently more efficient than the ML estimator despite the improved performance of the ML estimator when the sample size increases. However, computational ease and convenience favor the ML estimators. Keywords: maximum likelihood estimatorsbest linear unbiased estimatorslife-testingreliability

The pharmaceutical industry is currently interested in the population approach and population models, also known as mixed effects models and random effects models depending on the precise form. Population models are useful in that they can account for both withinand between-individual sources of variability and serial correlation within individual observations when analyzing unbalanced repeated measures data. The modelling of population pharmacodynamic or pharmacokinetic profiles typically involves nonlinear random effects models. Each individual's observations are modelled by identical (up to unknown parameter values) nonlinear regression models, with the distribution of the observations, or a transformation of the observations, about expected responses taken to be normal, with the degree of variability described by a variance model. Between-individual variability is modelled by a population distribution for the individual regression parameter values (random effects). In a parametric analysis the population distribution is taken to be normal, the parameters of which, along with the parameters of the variance model, are known as the population parameters. Maximum likelihood estimation of the population parameters for nonlinear random effects models was pioneered by Beal and Sheiner (1979), and since then a number of algorithms have appeared for approximate maximum likelihood, including Steimer et al. (1984), Lindstrom and Bates (1990), Beal and Sheiner (1992), and Mentre and Gomeni (1995). All of these algorithms are approximate in some way. For a summary see Beal and Sheiner (1992), Wolfinger (1993), Pinheiro and Bates (1994), and Davidian and Giltinan (1995). In this paper an EM algorithm for exact maximum likelihood estimation is introduced. An EM algorithm obtaining maximum likelihood estimates for linear random effects models was introduced by Dempster, Laird, and Rubin (1977). Laird and Ware (1982), Lindstrom and Bates (1988), Jennrich and Schluchter (1986), and Liu and Rubin (1994) all describe hybrid EM algorithms for the linear random effects model. A true EM algorithm for the linear model is described by Jamshidian and Jennrich (1993). Mentre and Gomeni (1995) describe an approximate EM algorithm for nonlinear random effects models and, from the algorithm given in this paper, it can be seen clearly how their approximations arise. The present algorithm uses Monte Carlo methods to perform the E step, a strategy previously adopted in an altogether different model by Guo and Thompson (1994). Guo and Thompson require a Gibbs sampler, that is, a Markov chain Monte Carlo method for their E step, but the present algorithm uses independent samples. In Section 2 of this paper the nonlinear random effects model is described. Section 3 gives the EM algorithm without random effect covariates, while Section 4 gives the modified algorithm in the

The class of generalized linear models is extended to allow for correlated observations, nonlinear models and error distributions not of the exponential family form. The extended class of models include a number of important examples, particularly of the composite transformational type. Large-sample inference and maximum likelihood estimation for the extended class of generalized linear models are discussed, and the analysis of deviance is generalized to the extended class of models. Calculation of the maximum likelihood estimate for a general likelihood by Fisher's scoring method and a related method is considered, and the relation with the Gauss–Newton method is discussed.

Beta regression model is used for modeling proportions measured on a continuous scale; its parameters are estimated with the maximum likelihood method. Classical regression models, such as linear regression model and nonlinear regression models like logistic regression are not suitable for such situations. As in linear regression model, the independent variables are assumed to be uncorrelated if this assumption is not met, then the multicollinearity appears. Multicollinearity problem means that there is a near dependency between the independent variables. Biased estimators are commonly used for correcting the multicollinearity problem. In this study, we propose a generalized biased estimator for correcting multicollinearity in beta regression that is generalize beta ridge regression estimator (GBRRE). The performance of the proposed generalized biased estimator is evaluated theoretically via the matrix mean squared errors and the scalar mean squared errors; and practically using a Monte Carlo simulation study. The simulation results show that the optimal shrinkage estimator is K1 and the worst one is K2. Also, the proposed generalized estimator is applied to a real data set of pre-university education students in Egypt during the academic year (2018/2019) and we found the application results agree with the simulation results. Finally based on the results of the simulation study and the application the performance of the suggested generalized biased estimator is better than maximum likelihood estimators.

Spatial two-stage designs for phase II clinical trials

Sample size modifications in the interim analyses of an adaptive design can inflate the type 1 error rate, if test statistics and critical boundaries are used in the final analysis as if no modification had been made. While this is already true for designs with an overall change of the sample size in a balanced treatment-control comparison, the inflation can be much larger if in addition a modification of allocation ratios is allowed as well. In this paper, we investigate adaptive designs with several treatment arms compared to a single common control group. Regarding modifications, we consider treatment arm selection as well as modifications of overall sample size and allocation ratios. The inflation is quantified for two approaches: a naive procedure that ignores not only all modifications, but also the multiplicity issue arising from the many-to-one comparison, and a Dunnett procedure that ignores modifications, but adjusts for the initially started multiple treatments. The maximum inflation of the type 1 error rate for such types of design can be calculated by searching for the “worst case” scenarios, that are sample size adaptation rules in the interim analysis that lead to the largest conditional type 1 error rate in any point of the sample space. To show the most extreme inflation, we initially assume unconstrained second stage sample size modifications leading to a large inflation of the type 1 error rate. Furthermore, we investigate the inflation when putting constraints on the second stage sample sizes. It turns out that, for example fixing the sample size of the control group, leads to designs controlling the type 1 error rate.

Ordinal regression is used to model the ordinal response variable as functions of several explanatory variables. The most commonly used model for ordinal regression is the proportional odds model (POM). The classical technique for estimating the unknown parameters of this model is the maximum likelihood (ML) estimator. However, this method is not suitable for solving problems with extreme observations. A robust regression method is needed to handle the problem of extreme points in the data. This study proposes Huber M-estimator as a robust method to estimate the parameters of the POM with a logistic link function and polytomous explanatory variables. This study assesses ML estimator performance and the robust method proposed through an extensive Monte Carlo simulation study conducted using statistical software, R. Measurement for comparisons are bias, RMSE, and Lipsitzs' goodness of fit test. Various sample sizes, percentages of contamination, and residual standard deviations are considered in the simulation study. Preliminary results show that Huber estimates provide the best results for parameter estimation and overall model fitting. Huber's estimator has reached a 50% breakdown point for data containing extreme points that are quite far from most points. In addition, the presence of extreme points that have only a distance of two times far from most points has no major impact on ML estimates. This means that the estimates for ML and Huber may yield the same results if the model's residual values are between -2 and 2. This situation may also occur for data with a percentage of contamination below 5%.

The Multiple Comparison Procedures with Modeling Techniques (MCP-Mod) framework has been recently approved by the U.S. Food, Administration, and European Medicines Agency as fit-for-purpose for phase II studies. Nonetheless, this approach relies on the asymptotic properties of Maximum Likelihood (ML) estimators, which might not be reasonable for small sample sizes. In this paper, we derived improved ML estimators and correction for their covariance matrices in the censored Weibull regression model based on the corrective and preventive approaches. We performed two simulation studies to evaluate ML and improved ML estimators with their covariance matrices in (i) a regression framework (ii) the Multiple Comparison Procedures with Modeling Techniques framework. We have shown that improved ML estimators are less biased than ML estimators yielding Wald-type statistics that controls type I error without loss of power in both frameworks. Therefore, we recommend the use of improved ML estimators in the MCP-Mod approach to control type I error at nominal value for sample sizes ranging from 5 to 25 subjects per dose.

ABSTRACTSinh-normal/independent distributions are a class of symmetric heavy-tailed distributions that include the sinh-normal distribution as a special case, which has been used extensively in Birnbaum–Saunders regression models. Here, we explore the use of Markov Chain Monte Carlo methods to develop a Bayesian analysis in nonlinear regression models when Sinh-normal/independent distributions are assumed for the random errors term, and it provides a robust alternative to the sinh-normal nonlinear regression model. Bayesian mechanisms for parameter estimation, residual analysis and influence diagnostics are then developed, which extend the results of Farias and Lemonte [Bayesian inference for the Birnbaum-Saunders nonlinear regression model, Stat. Methods Appl. 20 (2011), pp. 423-438] who used the Sinh-normal/independent distributions with known scale parameter. Some special cases, based on the sinh-Student-t (sinh-St), sinh-slash (sinh-SL) and sinh-contaminated normal (sinh-CN) distributions are discussed in detail. Two real datasets are finally analyzed to illustrate the developed procedures.

On diagnostics in symmetrical nonlinear models