Bioequivalence and Bioavailability Forum • Sample size for widened scaled ABE limits

Sample size for widened scaled ABE limits [🇷 for BE/BA]

posted by d_labes – Berlin, Germany, 2011-01-17 14:19 (5637 d 07:04 ago) – Posting: # 6427
Views: 34,747

Ahoy my dear Capt'n,

❝ Wouldn't it be nice to include an option for (but not replace with) sample size calculation with adaptation to CI-widening ad modum the new BE guideline in Europe?

THX for your suggestion.

Theoretically the power of scaled ABE evaluation (if it could be done exact :cool:

) and therefore the sample size is independent of the variability. Therefore it should be enough to tabulate sample sizes for different powers to achieve. For this reason the FDA has discussed 24 or 32 subjects for scaled ABE. See this post. But don't know where these numbers exactly came from.

Of course the 50% CV cut-off of the EMA complicates the situation.
Moreover the widened limits are only an approximation to the problem.
The constraint "point estimate within 0.8 - 1.25" is not part of the classical power considerations.

❝ It would be easy enough to internally adapt the theta's where the input CV is in the 30%-50% range and the design is ref-replicated.

require(PowerTOST)

CV  <- 0.3

CVr <- CV

if (CV>0.5) CVr <- 0.5

if (CV>=0.3) theta1 <- exp(-0.760*CV2se(CVr)) else theta1 <- 0.8

# change 0.76 to log(1.25)/CV2se(0.3) if you prefer higher precision

# for the regulatory constant

# change 0.76 to log(1.25)/0.25 and comment out the 4. code line

# if you prefer FDA's widened limits

sampleN.TOST(CV=CV,theta0=0.95,theta1=theta1,logscale=TRUE, design="2x3x3")

Easy enough for the programmer of the famous EFG :-D

, although externally adapted?

Lets see what the results are:
# Targetpower=0.8, theta0=0.95, alpha=0.05, design=2x3x3 partial replicate
Regulatory body: EMA k=0.760


    CV   theta1  theta2 Sample size Achieved power

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

 0.275 0.800000 1.25000          27       0.841451

 0.299 0.800000 1.25000          30       0.822751

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

 0.300 0.800030 1.24995          30       0.820245  # limits not exact 0.8 - 1.25

 0.325 0.785978 1.27230          30       0.833297

 0.350 0.772322 1.29480          27       0.802139

 0.400 0.746177 1.34016          27       0.818089

 0.450 0.721545 1.38591          27       0.829135

 0.500 0.698368 1.43191          27       0.837096

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

 0.550 0.698368 1.43191          30       0.811407

 0.600 0.698368 1.43191          36       0.826497

 0.650 0.698368 1.43191          39       0.802684

 0.700 0.698368 1.43191          45       0.812494

Regulatory body: FDA k=0.893


    CV   theta1  theta2 Sample size Achieved power

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

 0.275 0.800000 1.25000          27       0.841451

 0.299 0.800000 1.25000          30       0.822751

--------------------------------------------------- # discontinuity!

 0.300 0.769396 1.29972          21       0.828956

 0.350 0.738182 1.35468          21       0.846446

 0.400 0.708907 1.41062          21       0.857880

 0.450 0.681490 1.46737          21       0.865758

 0.500 0.655842 1.52476          18       0.805337

 0.550 0.631865 1.58262          18       0.809706

 0.600 0.609461 1.64079          18       0.813047

 0.650 0.588531 1.69915          18       0.815660

 0.700 0.568975 1.75755          18       0.817743

—
Regards,

Detlew

Complete thread:

Feature suggestion for bear and PowerTOST ElMaestro 2011-01-16 19:13
- Sample size for widened scaled ABE limitsd_labes 2011-01-17 13:19
  - 0.760 or... Helmut 2011-01-17 14:38
    - ... full precision is the question d_labes 2011-01-17 16:37
      - ... full precision is the question Helmut 2011-01-17 18:06
        
        OT: Number of horns on a unicorn d_labes 2011-01-18 08:32
        
        Goooogle Helmut 2011-01-18 11:44
  - Cadmium ElMaestro 2011-01-19 17:50
    - Never eaten Cadmium deliberately d_labes 2011-01-20 15:00
      - Never eaten Cadmium deliberately Helmut 2011-01-20 15:25
        
        Call of duty for simulants d_labes 2011-01-20 16:15
        
        Counterinuitive Helmut 2011-01-21 04:13
        
        Counterintuitive d_labes 2011-01-21 08:36
        
        Counterintuitive Helmut 2011-01-21 12:53
        
        Counterinuitive, but ... d_labes 2011-01-21 12:12
        
        Counterinuitive, but ... Helmut 2011-01-21 13:01
        
        Wow, Wow ... d_labes 2011-01-21 14:43
        
        Never eaten Cadmium deliberately ElMaestro 2011-01-21 12:59
        
        Simulants of the world, unite! Helmut 2011-01-21 14:05
        
        Simulants of the world, unite! ElMaestro 2011-01-21 14:52
        
        Hyslop, Howe, scaled ABE and that all d_labes 2011-01-21 15:28
        
        Hyslop, Howe, scaled ABE and that all ElMaestro 2011-01-21 15:45
        
        scABE and missings d_labes 2011-01-21 16:19
        
        Intuition Helmut 2011-01-21 18:41
      - Never eaten Cadmium deliberately ElMaestro 2011-01-20 15:34
        
        Use of Cadmium d_labes 2011-01-20 16:06
        
        Use of Cadmium ElMaestro 2011-01-20 16:52
        Use of Cadmium ElMaestro 2011-01-20 17:53