Bioequivalence and Bioavailability Forum

Dear Helmut,

this is a very eminent important post .

But I believe those to whom it really concerns unfortunately will not read it or are not able to read or duno understand its message .

❝ Contrary to 2×2×2 and parallel designs – where power can be directly calculated – for scaling we need simu­la­tions since the limits are not fixed, we have a restriction on the GMR, and an upper cap at 50% for EMA. The convergence is fine, but we still need 10⁵ simulations within every simulated study. This leads to ~10¹⁴ (110,000,000,000,000‼) simulations overall.

This is an optimistic (sic!) estimation since you forgot the sims necessary for the sample size estimation step of 2 ... 8 iterations with 10⁵ simulations each, since the start values of sample size search are naturally not as good as for the case of the classical sample size estimation.

So let us estimate more pessimistically (but may be too optimistically) an additional factor of 4 (one for the power monitoring step + 3 for the sample size estimation) within each of the simulations of your preferred grid of CV and n1.
This will then give, using your determined ~80 msecs, ~ 4x10¹⁴ sims x 80 ms =
3.2x 10¹³ secs = 533.333.333.333 min = 8.888.888.889 h = 370.370.370 days = 1.014.713 years!
calculated with the newest R version 3.2.0
(hope I got all the conversions using the thousands sparator "." correct, prove me wrong)
Oh what a weired calculation. Seems yesterday evening there was one beer too much . And alcohol impairs the ability of self critics.
Try it once more, hope now I got it right:
1.1×10⁹ sims each with 4x80 msecs for the power calculations =
5,866,667 min = 97,777.78 h = 4,074.074 days = 11.16185 years

Even if someone came out with a much more clever algo having a boost of 1E3 (thousand) faster than mine in PowerTOST (which I of course can't believe that it is possible to beat me to such an amount ) we all will not be alive we have to wait more than one month (~41 days) for noticing the result for one shot of alpha adjustment. And you need more than one ...

Just to make your message crystal clear!

If this all is necessary to be really done for a certain regulatory body (which one remains my secret ) remains an open question. As elsewhere said: Regulators are a bunch of strange people.