In a sequential clinical trial whose stopping rule depends on the primary endpoint, inference on secondary endpoints is an important long-standing problem. Ignoring the possibility of early stopping based on the primary endpoint may result in substantial bias. To address this problem, a commonly...

A hybrid method that combines Laplace's approximation and Monte Carlo simulations to evaluate integrals in the likelihood function is proposed for estimation of the parameters in nonlinear mixed effects models that assume a normal parametric family for the random effects. Simulations show that...

A nonparametric approach is developed herein to estimate parameters in nonlinear mixed effects models. Asymptotic properties of the nonparametric maximum likelihood estimators and associated computational algorithms are provided. Empirical Bayes estimators of functionals of the random effects...

A new ordering scheme for defining quantiles of the multivariate distribution of a stopping time and a stopped stochastic process is introduced. This ordering scheme is used in conjunction with resampling methods to construct confidence intervals for a population mean following a group...