Bioequivalence and Bioavailability Forum

Hi Marianna,

❝ We used data from the article: "Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and ❝ levonorgestrel-containing contraceptives with oral or subdermal administration route" Hofmann et. al, 2020.

❝ But the point still the number of subjects in this BE/BA study, because in this case, parallel design needs an intra+inter CV%.

Actually you need CV_total. That’s not the sum (or average) of both. You need to average the variances and back-convert them to a CV. In :

pooling <- function(CV.inter, CV.intra) {
  CV2var <- function(CV)  return(log(CV^2 + 1))
  var2CV <- function(var) return(sqrt(exp(var) - 1))
  return(var2CV(mean(c(CV2var(CV.inter), CV2var(CV.intra)))))
}
CV.inter <- 0.80
CV.intra <- 0.40
CV.total <- pooling(CV.inter, CV.intra)
cat("CV.inter =", sprintf("%.2f%%", 100 * CV.inter),
    "\nCV.inter =", sprintf("%.2f%%", 100 * CV.intra),
    "\nCV.total =", sprintf("%.2f%%", 100 * CV.total), "\n")

Gives

CV.inter = 80.00%
CV.inter = 40.00%
CV.total = 61.59%

❝ But in a scientific literature review, we don't find something like that.

I don’t have this article. If the study was performed in a parallel design, you have already CV_total. If it was not reported, you can calculate it from the confidence interval and the sample size by the function CVfromCI() in PowerTOST. If it was a crossover (very, very unlikely), use the code above.

❝ A suggestion about mitigating the error in subject number determination?

Not sure what you mean by that. Perhaps this article helps.