Bioequivalence and Bioavailability Forum

Dear Helmut,

Thank you very much for your reply, ICH M13A has a very clear description, thank you very much for sharing the case of missing data processing for multiple treatment groups.

❝ ❝ 2. For PK parameter analysis, can at least one period data to be included in PK parameter analysis?

❝ Not sure what you mean. Can you reword / elaborate?

❝ In a mixed effects model you could include the data but the result will be very similar (often identical) to a fixed effects model of complete data only (ANOVA).

My so-called PK parameter analysis refers to the simple descriptive statistics of PK parameters (such as AUC, Cmax, Tmax, etc. for mean, standard deviation, median, minimum value, maximum value, etc.), which does not involve the BE evaluation between the two treatment, whether PK descriptive analysis set and BE evaluation set must be consistent?

BTW, in FDA draft guidance «Statistical Approaches to Establishing Bioequivalence Guidance for Industry» about handling missing data, it is described as "Statistical methods for handling missing data include complete case analysis, available case analysis, weighting methods, imputation, and model-based approaches... An available case analysis could be done using SAS PROC MIXED, which uses all observed data (e.g., in a two-way crossover study, uses all subjects with one or two complete periods of data)... Approaches for handling missing data and the statistical methods for the primary BE analysis (e.g., GLM vs. MIXED) should be pre-specified in the study protocol or SAP.".
Will FDA guidance be updated with the ICH M13A statistical perspective? Or will FDA accept the two pre-specified missing data handling methods?

Thank you very much!
Looking forward to your reply again.