Bioequivalence and Bioavailability Forum

Hello,

I need help finding a reference that gives methodology and assumptions for estimating between and within subject variabilities from total variability for a BE study.

Here are my specific conditions:

I have a variance estimate from a prior study. This study was a parallel design.

I need to use this variability to generate a power calc (samp size) for a x-over study. So I need to estimate the within subject variability using the variability estimate I have from the prior study.

For the purposes of this discussion, I am going to assume the variability estimate I have is the total variability we would expect to see when testing this drug.

I will also assume: total variability = between subject variability + within subject variability

Based on my experience I have found the split to be, in general, something like this:

Between subject variability = 50% to 70% of total variability
Within subject variability = 30% to 50% of total variability

I need help finding a reference that supports these assumptions. I recall having a reference many years ago but it has disappeared over the years.

Over the past 15+ years, these assumptions have served me well and to my recollection, have not been significantly off when powering a definitive study. I do understand that within subject variability can be larger than the between subject variability but these are not typical results and are rare in my experience. And if this is observed and the numbers are correct, there are big problems with the compound being tested!

Ahy help with finding a reference is much appreciated!

Thanks in advance!
Jack