Bioequivalence and Bioavailability Forum

Dear discutants!

Thanks to all (especially from Oberbavaria) for sharing your knowledge.
Seems a tiny step towards international harmonization .

One question is left, if I see this correct: The estimation method. EMA's crippled ANOVA(s), or FDA's mixed model approach, or intra-subject contrasts (ISC)?
Unfortunately I have no clue how to simulate FDA's mixed model approach avoiding time consuming subject data sims. ISC may be a substitute, at least w.r.t. the degrees of freedom.

For the aim of sample size estimation the differences (if any) are only marginal, but for evaluation of the TIE or other explorations of power it may count.
Upcoming PowerTOST version:
# Defaults: partial replicate design, regulator EMA
# sample size, GMR=0.9 (theta0)
# EMA's crippled ANOVA(s)
sampleN.scABEL(CV=0.3, print=FALSE, details=FALSE)
  Design alpha CVwT CVwR theta0 theta1 theta2 Sample size Achieved power Target power nlast
1  2x3x3  0.05  0.3  0.3    0.9    0.8   1.25          54        0.81593          0.8    54
# Evaluation via robust ISC
sampleN.scABEL2(CV=0.3, print=FALSE, details=FALSE)
  Design alpha CVwT CVwR theta0 theta1 theta2 Sample size Achieved power Target power nlast
1  2x3x3  0.05  0.3  0.3    0.9    0.8   1.25          54        0.80765          0.8    54
# Now power at border of widened acceptance limits (TIE), GMR=0.95
# EMA's crippled ANOVA(s)
power.scABEL(CV=0.3, n=24, theta0=scABEL(CV=0.3)[2], nsims=1e6)
[1] 0.069039
# Evaluation via 'robust' ISC
power.scABEL2(CV=0.3, n=24, theta0=scABEL(CV=0.3)[2], nsims=1e6)
[1] 0.07631