Bioequivalence and Bioavailability Forum

Hi ElMaestro,

❝ […] I have not come a across a scientific justification for avoiding random effects in BE.

Me not either – and I don’t expect to see one ever. Do you believe the mighty oracle has got one? The nicest explanation I know is by Gerard E. Dallal (giving an example about nurses measuring blood pressure by three different methods):

Factors can either be fixed or random. A factor is fixed when the levels under study are the only levels of interest. A factor is random when the levels under study are a random sample from a larger population and the goal of the study is to make a statement regarding the larger population.

In this example, method is a fixed factor. The purpose of this study is to examine these three methods of measuring blood pressure. There may be other methods, but they do not concern us here. When we are done, the hope is to make a statement comparing these three methods.

From the description of the study, the status of nurse is less clear. If the investigator cares only about these four nurses, nurse is a fixed factor. This might be the case where the study concerns the staff of a particular research unit and there is no goal of generalizing beyond the unit. Since only these four nurses matter, nurse is a fixed factor. However, it might be that the point of the study is to generalize the results to all nurses. In that case, these four nurses might be viewed as a random sample of the population of all nurses, making nurse a random factor.

One way to decide whether a factor is fixed or random is to ask what would happen if the study were repeated. If the same set of nurses would be used (as in the case of studying a particular research unit) the factor is fixed. If any set of nurses would do equally well, the factor is random.

Read subject instead of nurse and treatment instead of method… That’s BE! Do we want to make inferences about a larger population and/or run similar studies? I always did so.
With all effects fixed EMA should at least be as honest to redefine type I error in BE and replace “patient’s risk” or “consumer’s risk” by “volunteer’s risk”.