Bioequivalence and Bioavailability Forum

Hi sury,

❝ I want to include the deletti tables in my SOP references …

I don’t understand. You have already an SOP without references – what does it say? How do you estimate a sample size right now?

These tables for α 0.05 (90% CI), 70/80/90% power and

• CV 5–30% (step size 5%), T/R-ratio 0.85–1.20 (step size 0.05);
  for acceptance 80.00–125.00%¹
  
• CV 5–20% (step size 2.5%), T/R-ratio 0.925–1.075 (step size 0.025);
  for acceptance range 90.00–111.11%²
  
• CV 15–60% (step size 5%), T/R-ratio 0.75–1.35 (step size 0.05);
  for acceptance range 70.00–142.86%²

are hopelessly behind state of the art!

Since power is nonlinear, you can’t easily interpolate if you are interested in anything not given in the tables. What if you want another α (two-stage adaptive and group-sequential designs) or an acceptance range of 75.00–133.33% (applicable in some jurisdictions for C_max)?
NB, if you are interested in reference-scaling (FDA: RSABE, EMA: ABEL) you need yet other tables (covered designs: TRR|RTR|RRT and TRTR|RTRT).³ No tables exist for other designs (e.g., TRT|RTR – which is better than the lousy partial replicate), Health Canada’s ABEL, and the FDA’s RSABE for NTIDS.

Hence, I strongly suggest to opt for software, i.e., package PowerTOST⁴ for which supports all of those (plus paired and parallel designs, non-inferiority/-superiority, Fieller’s CI of ratios, dose-proportionality, …).

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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(8):287–90.
   
3. Tóthfalusi L, Endrényi L. Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs. J Pharm Pharmaceut Sci. 2011;15(1):73–84. open access.
   
4. Labes D, Schütz H, Lang B. PowerTOST: Power and Sample Size Based on Two One-Sided t-Tests (TOST) for (Bio)Equivalence Studies. 2018-04-12;1.4-7.
   https://cran.r-project.org/package=PowerTOST.