Testing non-inferiority for accuracy of quantitative microbiological methods

Authors Edwin van den Heuvel, Maliheh Heidari, Kathrin Möllenhoff and Pieta IJzerman-Boon compare statistical analysis methods for determining comparable accuracy of alternate and compendial microbiological methods.

FOR THE VALIDATION of alternate microbiological methods, it is necessary to demonstrate that the accuracy of the alternate method is equivalent or non-inferior to the compendial method. Based on an experiment with multiple test samples from different concentrations per microbiological method, researchers often conduct difference testing assuming normally distributed data. Moreover, researchers typically conduct balanced experiments, with the same number of samples per concentration. In this paper we evaluate two statistical approaches for demonstrating non-inferiority using Poisson distributed counts. The first approach does not make any assumptions on the relation between the mean enumeration and the concentration. The paper shows that (optimal) sample sizes for this approach depend on the selected concentrations, which can suggest a non-balanced experiment. The second approach models the relation between the mean counts and the concentration for both microbiological methods with the non-linear Mitscherlich function. This model-based approach has more power than the non-model-based approach for testing non-inferiority.