Bioequivalence and Bioavailability Forum

Hi John John,

❝ Cmax   CVintrasub (0.387)  Ratio(%Ref) (81.439)


❝                BEQ (70.162-94.529)

Later you wrote:

❝ We have worked with CI of 94.12 and alpha 0.0294

I don’t think so; with your data:

library(PowerTOST)
round(100*CI.BE(alpha=0.0294, pe=0.81439, CV=0.387, n=36), 3)
 lower  upper
68.558 96.740

But:

round(100*CI.BE(alpha=0.0500, pe=0.81439, CV=0.387, n=36), 3)
 lower  upper
70.173 94.514

Talk to your statistician. I suggest to read the papers again (before designing a study & writing the pro­to­col / SAP) in order to get the analysis right.

Adding to this post:

find_alpha <- function(x) {
  require(PowerTOST)
  CI     <- CI.BE(alpha=alpha, pe=pe, CV=CV, n=n)
  closer <- CI[which.min(abs(CI - 1))]
  CI.BE(alpha=x, pe=pe, CV=CV, n=n)[names(closer)]-1
}
n     <- 36
pe    <- 0.81439
CV    <- 0.387
alpha <- 0.0294
p     <- uniroot(find_alpha, interval=c(1e-6, 0.5),
           tol=1e-8)$root
if (p < alpha) {
  cat(paste0("\n100% is not included in the ",
    "100(1\u002d2\u03b1) = ", 100*(1-2*alpha),
    "% confidence\ninterval; treatments are ",
    "significantly different (p ", signif(p, 4), ").\n\n"))
  } else {
  cat(paste0("\nTreatments are not significantly different ",
    "(p ", signif(p, 4), ").\n\n"))
}

100% is not included in the 100(1-2α) = 94.12% confidence
interval; treatments are significantly different (p 0.01289).

Do you really think that it is reasonable to continue?