Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

Convective Filmwise Condensation of R-11 inside a Vertical Tube

Partial condensation of refrigerant R-11 was experimentally and theoretically studied. The test apparatus consisted of two concentric tubes, with the vapor flowing downward in the inner tube and the cooling water in the annular space in countercurrent direction. By using the available dimensionless correlation, the mean heat transfer coefficient of the cooling water was determined, and then the mean condensationheat transfer coefficient was calculated from the overall heat transfer coefficient.The model of a homogeneous two-phase mixture of liquid and vapor, and Prandtl's principle of analogy between the momentum and heat transfer were used to establish the type of the correlation. Adopting the methods of the gradually linear regression and F-level evidence testing, the present paper proposed the dimensionless correlation to predict the relationship among the mean Nusselt number, Prandtl number, Kutateladze number and the dimensionless tube length.     

Bayesian quantile regression for single-index models

Using an asymmetric Laplace distribution, which provides a mechanism for Bayesian inference of quantile regression models, we develop a fully Bayesian approach to fitting single-index models in conditional quantile regression. In this work, we use a Gaussian process prior for the unknown nonparametric link function and a Laplace distribution on the index vector, with the latter motivated by the recent popularity of the Bayesian lasso idea. We design a Markov chain Monte Carlo algorithm for posterior inference. Careful consideration of the singularity of the kernel matrix, and tractability of some of the full conditional distributions leads to a partially collapsed approach where the nonparametric link function is integrated out in some of the sampling steps. Our simulations demonstrate the superior performance of the Bayesian method versus the frequentist approach. The method is further illustrated by an application to the hurricane data.     

Understanding increments in model performance metrics

The area under the receiver operating characteristic curve (AUC) is the most commonly reported measure of discrimination for prediction models with binary outcomes. However, recently it has been criticized for its inability to increase when important risk factors are added to a baseline model with good discrimination. This has led to the claim that the reliance on the AUC as a measure of discrimination may miss important improvements in clinical performance of risk prediction rules derived from a baseline model. In this paper we investigate this claim by relating the AUC to measures of clinical performance based on sensitivity and specificity under the assumption of multivariate normality. The behavior of the AUC is contrasted with that of discrimination slope. We show that unless rules with very good specificity are desired, the change in the AUC does an adequate job as a predictor of the change in measures of clinical performance. However, stronger or more numerous predictors are needed to achieve the same increment in the AUC for baseline models with good versus poor discrimination. When excellent specificity is desired, our results suggest that the discrimination slope might be a better measure of model improvement than AUC. The theoretical results are illustrated using a Framingham Heart Study example of a model for predicting the 10-year incidence of atrial fibrillation.     

Optimal designs for exponential regression

This paper is concerned with the optimal design problem for the particular case of non-linear parametrisation:the parameters to be estimated are included in exponents.Some properties of locally optimal designs as functions of estimated parameters are investigated and a table of such designs in given.We consider also designs to be optimal in the sense of minimax approach.     

Exact distribution of the MLEs of the parameters and of the quantiles of two-parameter exponential distribution under hybrid censoring

Epstein [Truncated life tests in the exponential case, Ann. Math. Statist. 25 (1954), pp. 555–564] introduced a hybrid censoring scheme (called Type-I hybrid censoring) and Chen and Bhattacharyya [Exact confidence bounds for an exponential parameter under hybrid censoring, Comm. Statist. Theory Methods 17 (1988), pp. 1857–1870] derived the exact distribution of the maximum-likelihood estimator (MLE) of the mean of a scaled exponential distribution based on a Type-I hybrid censored sample. Childs et al. [Exact likelihood inference based on Type-I and Type-II hybrid censored samples from the exponential distribution, Ann. Inst. Statist. Math. 55 (2003), pp. 319–330] provided an alternate simpler expression for this distribution, and also developed analogous results for another hybrid censoring scheme (called Type-II hybrid censoring). The purpose of this paper is to derive the exact bivariate distribution of the MLE of the parameter vector of a two-parameter exponential model based on hybrid censored samples. The marginal distributions are derived and exact confidence bounds for the parameters are obtained. The results are also used to derive the exact distribution of the MLE of the pth quantile, as well as the corresponding confidence bounds. These exact confidence intervals are then compared with parametric bootstrap confidence intervals in terms of coverage probabilities. Finally, we present some numerical examples to illustrate the methods of inference developed here.