Bioequivalence and Bioavailability Forum

Dear All,

One question for the least square mean calculation for the fully replicate design as per USFDA in SAS.

We performed the statistical analysis using the code provided in progesterone guideline and Least square mean values of AUCi parameter for the Test and Reference are 6.112006 and 6.111151 respectively.

Unfortunately, after statistical analysis, one error was identified by sponsor in bio-analysis of sample in test formulation. Only one value in particular time point of one period in one subject got changed. Hence, Statistical analysis performed again and it was observed that Least square mean values of AUCi for Test and Reference are 6.111382 and 6.110883. The change in the value of test product results in the change in LSM value in reference product!!

The question is, reference product data remain the same, there is not a single value change in reference data then why Least square mean value of reference product changed AUCi parameter. Why this is affecting the reference data?

I have also perform the same experiments in two way study design but in that if I am changing any reference data it is not impacting on least square test data.

Please share your thoughts …

Thanks !!
Jaimik

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Edit: Category changed; see also this post #1. [Helmut]