Bioequivalence and Bioavailability Forum

Dear Ahmed,

since you have quoted ANVISA, have a look at the example given at page 9 of the document. You must apply an iterative method, in order to get a sample size estimate (because the t-dis­tri­bution depends on the degrees of freedom and therefore, on the sample size itself).
Anyhow, ANVISA’s example is derived from Chow and Liu’s textbook, which refers to a linear (addi­tive) model on untransformed data – which is useless in our case.

For sample size estimation of log-transformed data (multiplicative model), you may either use tables^1,2 or approximations.^3,4
Approximations may give slightly larger samples size in a few cases (generally give the same num­bers than exact values from tables), but give you the freedom of choosing any deviation of test from reference, whereas tables give only a step size of 5%.
Another option is software, e.g., StudySize, PASS, NQuery Advisor,…

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1. Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharm Ther Toxicol. 1991;29(1):1–8.
   
2. Diletti E, Hauschke D, Steinijans VW. Sample size determination: Extended tables for the multiplicative model and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43. Int J Clin Pharm Ther Toxicol. 1992;30/Suppl.1:S59–62.
   
3. Hauschke D, Steinijans VW, Diletti E, Burke M. Sample Size Determination for Bioequivalence Assessment Using a Multiplicative Model. J Pharmacokin Biopharm 1992;20(5):557–61.
   
4. Chow SC, Wang H. On Sample Size Calculation in Bioequivalence Trials. J Pharmacokin Pharmacodyn. 2001;28(2):155–69.
   Errata: J Pharmacokin Pharmacodyn. 2002;29(2):101–2.