Bioequivalence and Bioavailability Forum

Hi Jack,

❝ 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.

Stop searching. IMHO there is none. See this presentation (slides 18–20).

❝ 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.

So far so good.

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

If you mean by variability the variances (and not the CVs), you are almost there.

❝ Between subject variability = 50% to 70% of total variability

❝ Within subject variability = 30% to 50% of total variability

OK, this is one of the often quoted ‘rules of thumb’ which have no statistical background. If it worked in your experience, you have been lucky.
See slide 20 for other examples and this thread as well.

A justification of any ‘rule’ would a require a sufficiently high correlation between intra- and inter-subject variability. What I have seen in my studies (checked ~150 until I got bored) is R² of 0.5…

❝ […] I recall having a reference many years ago but it has disappeared over the years.

Too bad. Would have been nice to dissect it.

❝ 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.

Again: Lucky you!

❝ 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!

Not necessarily the drug, but it might be the formulation as well. No very uncommon for PPIs.