Bioequivalence and Bioavailability Forum

dear hs !

thank you for comment, I think I mixed up definition of data sets and handling of missing values, here is my point of view in more detail. based on my experience with these kind of things usually two data sets are used (artificial example for definitions of a cross-over trial):

Full analysis data set (intent-to-treat): subjects that were randomized and received at least one study treatment.

Per-protocol analyses data set: subjects that were randomized, met all inclusion criteria, were dosed according to the protocol, received both treatments with measurements at all assessment time points with both study drugs, etc.

based on these example definitions, handling of missing values is applicable for the full analyses dataset only. handling of missing values for calculation specific PK parameters (e.g. primary endpoint) and circumstances when these approach will be applied should be stated in the protocol (decision tree) or can be documented after a blinded review of the data.

for PK analyses, both data sets are analyzed and the results for the full analyses data set is the more important as pointed out by the ICH E9 guideline (i.e. primary analysis). for safety analyses, only the full analysis data set is used.

best regards

martin