Evaluation of tests based on individual versus population modeling to compare dissolution curves.

This study is aimed at comparing dissolution curves obtained for several batches of sustained release formulations of octreotide, a somatostatin analog used in acromegaly. We evaluated four tests to compare the parameters of two series of curves: a Mann-Whitney-Wilcoxon test comparing individual estimates; a likelihood ratio test after population analysis (NONMEM), and two Wald tests using population parameters estimated by two-stage methods. The four approaches were evaluated by simulations. The Mann-Whitney-Wilcoxon test and the population approach had adequate type-I error, and the latter provided the highest power under the alternatives simulated. The two-stage method including the uncertainty on individual estimates was disappointing.