Bioequivalence

library(nlme)
# 2*2 cross-over design
auc11<-c(78.8,67.5,48.6,14.6,59.9,95.9,51.5,42,23.5,37)
auc12<-c(36.7,43.6,198.5,70.4,33.1,27.1,50.1,26.9,38.3,120.9)
auc21<-c(125.3,94.6,66.3,26.9,82.6,91.8,72.4,74.3,41.7,58.2)
auc22<-c(24.9,42.5,99.8,49.7,12.6,9.1,22,9,10.6,67.3)

auc<-c(auc11,auc12,auc21,auc22)
Sequence<-as.factor(rep(c(rep(1,10),rep(2,10)),2))
subject<-rep(1:20,2)
period<-as.factor(c(rep(1,20),rep(2,20)))
trt<-c(rep("test",10),rep("ref",20),rep("test",10))

AUC<-data.frame(Sequence,subject,period,trt,auc)

lme(log(auc)~Sequence+period+trt, random=~1|subject/Sequence, data=AUC)