Sample‐size calculations for multi‐group comparison in population pharmacokinetic experiments

This paper describes an approach for calculating sample size for population pharmacokinetic experiments that involve hypothesis testing based on multi‐group comparison detecting the difference in parameters between groups under mixed‐effects modelling. This approach extends what has been described for generalized linear models and nonlinear population pharmacokinetic models that involve only binary covariates to more complex nonlinear population pharmacokinetic models. The structural nonlinear model is linearized around the random effects to obtain the marginal model and the hypothesis testing involving model parameters is based on Wald's test. This approach provides an efficient and fast method for calculating sample size for hypothesis testing in population pharmacokinetic models. The approach can also handle different design problems such as unequal allocation of subjects to groups and unbalanced sampling times between and within groups. The results obtained following application to a one compartment intravenous bolus dose model that involved three different hypotheses under different scenarios showed good agreement between the power obtained from NONMEM simulations and nominal power. Copyright © 2009 John Wiley & Sons, Ltd.     

Faculty abstracts

Background. The Aging Males' Symptoms scale (AMS) is an internationally used scale to analyse health related quality of life (HRQoL). The aim of this paper is to provide evidence that the Nigerian AMS scale measures HRQoL with similar accuracy as in other language versions. We also intended to show the severity of complaints of aging in males in advanced old age. More generally, we aim to demonstrate that the Nigerian AMS scale is an applicable, validated, sensitive instrument to measure HRQoL in Nigeria.

Material. We performed a representative survey in Nigeria to get data of the AMS scale in a group of males in old age. The survey was a household-based population sample conducted in March 2006. The Nigerian data were compared with existing data from other European countries. Only community-based data were used for this comparison.

Results and discussion. The internal structure of the AMS (factorial analysis) was sufficiently similar with the comparison group of other countries in Europe to conclude that the scale really measures the same phenomenon. The sub-scores and total score correlations were high (0.8–0.9) but lower among the sub-scales (0.4–0.8). This suggests that the domains are not fully independent. The reliability (consistency) was found to be good and almost identical with European countries.

Mean scores of the Nigerian AMS did systematically differ from data of other European studies. There were much higher because of older age. The same applies for the population reference values obtained in Nigeria. It is the first time that population norm values are available for very old age.

Conclusion. The Nigerian AMS scale is a standardized HRQoL scale that showed good psychometric characteristics (reliability, validity) similar to other international versions. We suggest that the results obtained with the Nigerian AMS scale should be used preliminarily as reference for ‘norm values’ for highest age, i.e. in absence of other data. Confirmation in future studies is needed.