Improved inference on a scalar fixed effect of interest in nonlinear mixed-effects models

Likelihood-based inference on a scalar fixed effect of interest in nonlinear mixed-effects models usually relies on first-order approximations. If the sample size is small, tests and confidence intervals derived from first-order solutions can be inaccurate. An improved test statistic based on a modification of the signed likelihood ratio statistic is presented which was recently suggested by Skovgaard [1996. An explicit large-deviation approximation to one-parameter tests. Bernoulli 2, 145–165]. The finite sample behaviour of this statistic is investigated through a set of simulation studies. The results show that its finite-sample null distribution is better approximated by the standard normal than it is for its first-order counterpart. The R code used to run the simulations is freely available. © 2006 Elsevier B.V. All rights reserved.