Optimal Spiking Experiment for Noninferiority of Qualitative Microbiological Methods on Accuracy With Multiple Microorganisms

The European and United States Pharmacopoeia demand a noninferiority study on the detection of microorganisms when an alternate qualitative microbiological method is intended to replace the compendial microbiological method. However, without imposing any modeling assumptions or constraints, noninferiority studies require large numbers of test samples for a proposed noninferiority criterion of 0.7 or higher for each microorganism. When we can assume that the accuracy of the alternate method with respect to the compendial method is homogeneous across microorganisms, a joint statistical analysis of the data from all microorganisms can be used to help reduce the sample size dramatically. For this situation, we provide a test statistic for noninferiority, an optimal spiking experiment, and a sample size calculation approach under only mild modeling assumptions of the microorganism-specific detection proportions. We illustrate our approach on a real dataset and demonstrate good performance of our method using simulation studies.

Automated summary

The European and United States Pharmacopoeia require a noninferiority study to be conducted when considering an alternative microbiological method. By assuming the accuracy of the alternative method is homogeneous across microorganisms, a joint statistical analysis can help reduce the required sample size. This study provides a test statistic for noninferiority, an optimal spiking experiment, and a sample size calculation approach based on mild modeling assumptions of microorganism-specific detection proportions.