Bioequivalence and Bioavailability Forum

Hi Siva Krishna,

I guess 100% was not contained in the 90% CI, right?
If yes, you have a statistically significant difference which is clinically not relevant.¹ We abandoned testing for a statistically significant difference (see ElMaestro’s post) 33 (‼) years ago with Schuirmann’s TOST.² To quote Wasserstein et al.³

Don’t Say “Statistically Significant”

For which power did you plan the study? It might well be that

• the T/R-ratio was closer to 100% than assumed and/or
  
• the CV was lower than assumed and/or
  
• the dropout-rate was lower than anticipated.

Any of those (and their combinations) will lead to higher power and increases the chance of a statistically significant treatment effect.
See also the second part of this post. If you are in the lower right quadrants, you have high power and a statistically significant treatment effect is likely.

See also this article.

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1. \(\small{\Delta}\) = clinically relevant difference. Commonly 0.20 (20%). For NTIDs (EMA and other jurisdicions) \(\small{\Delta}\) 0.10, for C_max (Russian Federation, EEU, GCC) \(\small{\Delta}\) 0.25. For HVD(P)s, where CV_wR >30%, \(\small{\Delta}\) >0.30 (scaled to the variability of the reference). The acceptance range for bioequivalence \(\small{\left \{\theta_1,\theta_2\right \}}\) is calculated by \(\small{\theta_1=1-\Delta}\), \(\small{\theta_2=(1-\Delta)^{-1}}\). If the 90% CI lies entirely within \(\small{\left \{\theta_1,\theta_2\right \}}\), the observed difference of the treatment effect is considered clinically not relevant – irrespective how wide the CI is or where the point estimate lies. A formulation with a PE of 100% (CI 80.00–125.00%) is as BE as another with a PE of 85% (CI 80.00–90.31%). In the former case you were extremely lucky and in the second you have a statistically significant difference (100% not contained in the CI).
   
2. Schuirmann DJ. A comparison of the Two One-Sided Tests Procedure and the Power Approach for Assessing the Equivalence of Average Bioavailability. J Pharmacokin Biopharm. 1987; 15(6): 657–80. doi:10.1007/BF01068419.
   
3. Wasserstein RL, Schirm AL, Lazar NA. Moving to a World Beyond “p < 0.05”. Am Stat. 2019; 73(sup1): 1–19. doi:10.1080/00031305.2019.1583913. Open access.