Bioequivalence and Bioavailability Forum • SABE or Normal BE?

SABE or Normal BE? [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2013-02-20 16:45 (4450 d 20:32 ago) – Posting: # 10080
Views: 12,320

Hi Luv,

sorry for cutting in.

❝ ❝ FDA wants you to compare the intrasubject variation between test and reference which full replicate will give. […]

❝

❝ Just a thought, What if the variability in the reference product is higher than test? ;-)

Wouldn’t matter since variabilities are compared by a one-sided test. In other words, the variability of the test must not be significantly larger than the one of the reference. Smaller is fine.

❝ I tried using FARTSSIE 17 to do some random calculations

❝

❝ Lower Equivalence Limit 90.0%

❝ Upper Equivalence Limit 111.1%

❝ …

❝ Required Sample Size 168

Nope. For CV_WR 20% (σ_WR 0.1980422) limits are upscaled from 0.9/1.11111 to 0.8116742/1.232021. Then FARTSSIE agrees with PowerTOST.

PowerTOST

sampleN.TOST(CV=0.2,theta0=0.95, theta1=0.8116742, theta2=1.232021, design="2x2x2")

+++++++++++ Equivalence test - TOST +++++++++++

            Sample size estimation

-----------------------------------------------

Study design:  2x2 crossover

log-transformed data (multiplicative model)



alpha = 0.05, target power = 0.8

BE margins        = 0.8116742 ... 1.232021

Null (true) ratio = 0.95,  CV = 0.2



Sample size (total)

 n     power

22   0.810558

FARTSSIE

Expected µT/µR Ratio     95%-105.3%

Lower Equivalence Limit  81.16742%

Upper Equivalence Limit 123.2021%

sw                        0.1980422

n                        22

n-2                      20

t(1-alpha,n-2)            1.724718004

tau2                     -4.353385162

tau1                      2.635367015

Probt(2)                  0.994693186

Probt(1)                  0.184134808

1-b                       0.810558378



Required Sample Size     22

But: For the FDA a full replicate design is mandatory anyway. Of course you are right for EMA where for some NTIDs (tacrolimus: AUC, ciclosporine: AUC and C_max) the acceptance range is fixed to 90.00–111.11%.

❝ For A full replicate study […]

I wouldn’t use FARTSIE for replicate designs any more because the sample size is estimated for a 2×2×2 design and afterwards set to 50% for full replicates and 75% for three-period designs. That’s just approximatively correct.

—
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Helmut Schütz

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Complete thread:

SABE or Normal BE? luvblooms 2013-02-19 05:07 [RSABE / ABEL]
- FDA: rSABE for NTIDs Helmut 2013-02-19 11:05
- SABE or Normal BE? jag009 2013-02-19 15:23
  - Sample size? Helmut 2013-02-19 17:25
  - SABE or Normal BE? luvblooms 2013-02-20 05:26
    - SABE or Normal BE? jag009 2013-02-20 15:20
    - SABE or Normal BE?Helmut 2013-02-20 15:45
      - SABE or Normal BE? ElMaestro 2013-02-20 16:08
        
        SABE or Normal BE? jag009 2013-02-21 17:10
        
        FDA’s example data sets Helmut 2013-02-21 17:18
        
        FDA’s example data sets jag009 2013-02-21 20:14
        
        FDA’s example data sets Helmut 2013-02-21 22:42
        
        FDA’s example data sets jag009 2013-02-22 15:46
        
        FDA’s example data sets Helmut 2013-02-22 16:33