Bioequivalence and Bioavailability Forum

Hi Anu,

❝ Refernce Formulation (LSM,SD)=(12.225,0.171)

❝ Test Formulation (LSM,SD)=(11.540,0.171)

Identical SDs? Your variability is unbelievably low (CV ~1.44%). In the linked study the CV was ~20.4% – which is already pretty low for phosphate excretion. Even if your values are the SEMs (not the SDs) I still doubt CVs of ~6.6%.

❝ As for the calculation of Pivotol study sample size we require (CV %, Point Estimate (T/R)) from Pilot study usually.

If you want to follow the method of the linked study you need CV% and the difference (!) T–R, not the ratio T/R.

❝ I have no idea how to go for the sample size calculation for this study from pilot results so available. How we can calculate sample size for Pivotal Study in this case?

You need the intrasubject CV from your study (untransformed data). If it is not given in the study report calculate it as CV_intra = √MSE/LSM_R.

❝ Also in the given link dint get how they have calculated, PD equivalence was to be claimed if the 90% CI was completely contained within the critical reference range of (-3.47, 3.47).

❝ The numbers in red. Which in our study is (-2.44 to 2.44)

❝ How the calculations done?

              n     T (SD)      R (SD)    80–120% of R   AR* for T–R  90% CI of T–R
linked study  49  16.01±3.40  17.35±3.39  13.88–20.82   –3.47, +3.47  –3.17, –0.80
your study    21  11.54±0.17  12.23±0.17   9.78–14.67   –2.45, +2.45  –1.07, –0.30

Note that both studies were imbalanced. In the imbalanced case generally the LSM of the difference ≠ the difference of treatment means.
               T–R   LSM
linked study  –1.34 –1.98
your study    –0.69 –0.69

Check your calculations.

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• AR = (1±0.2)×R – R = [13.88, 20.82] – 17.35 = –3.47, +3.47