Bioequivalence and Bioavailability Forum • If it is real: results

If it is real: results [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2013-03-29 00:20 (4483 d 10:13 ago) – Posting: # 10305
Views: 25,892

Hi Martin!

❝ IMHO: yes as this is a constant and should not dependent on the number of simulation runs.

Oh yes, sure. Sorry for my stupidity.

❝ Ps.: ... and yes its the same guy who is famous for publicly calling some approaches “bullshit” :-D

I always thought he should work on his social skills.

Here the results of my sim’s for target α 0.05. Partial and full replicate designs, n=24/48.

[image]

The FDA’s method would lead to a large α-inflation (as presented by Detlew above) for CV_WR ≤30%. This could be corrected by adjusting α. However, since scaling is only allowed for CV_WR >30% nothing has to be done. Like the conventional TOST the test gets more conservative with increasing CV (and n).

[image]

The EMA’s method is another cup of tea. α-inflation is seen up to 45%! The test is closer to the nominal level than the FDA’s.
Interesting the behavior of the partial replicate with n=24. :confused:

Code (10–25 iterations to reach convergence, runtime on my machine 15–45 seconds depending on design, n, CV):

require(PowerTOST)

reg   <- "EMA"   # "EMA" for ABEL or "FDA" for scABE

CV    <- 0.300   # intra-subject CV of reference

n     <- 24      # total sample size

                 # in case of imbalanced sequences use a vector:

                 # e.g., c(n1,n2,n3)

des   <- "2x3x3" # partial: "2x3x3" full: "2x2x4"

                 # for others see known.designs()

print <- TRUE    # intermediate results

if (reg == "EMA") { # scABEL

  ifelse (CV <= 0.5, GMR <- exp(0.7601283*CV2se(CV)),

                     GMR <- exp(0.7601283*CV2se(0.5)))

  if (CV <= 0.3) GMR <- 1.25

  } else {          # RSABE

  ifelse (CV > 0.3, GMR <- exp(0.8925742*CV2se(CV)),

                    GMR <- 1.25)

}

nsims <- 1e6

prec  <- 1e-8    # precision of bisection algo

x     <- 0.05    # target alpha

nom   <- c(0.001, x)                # from conservative to target alpha

lower <- min(nom); upper <- max(nom)

delta <- upper - lower              # interval

ptm   <- proc.time()                # start timer

iter  <- 0

while (abs(delta) > prec) {         # until precision reached

  iter  <- iter + 1

  x.new <- (lower+upper)/2          # bisection

  if (reg == "EMA") {

    pBE <- power.scABEL(alpha=x.new, theta0=GMR, CV=CV,

                        n=n, design=des, nsims=nsims)

    } else {

    pBE <- power.RSABE(alpha=x.new, theta0=GMR, CV=CV,

                       n=n, design=des, nsims=nsims)

  }

  if (print) {                      # show progress

    if (iter == 1) cat(" i  adj. alpha       pBE\n")

    cat(format(iter, digits=2, width=2),

        format(x.new, digits=6, width=11, nsmall=7),

        format(pBE, digits=6, width=9, nsmall=6), "\n")

    if (.Platform$OS.type == "windows") flush.console()

  }

  if (abs(pBE - x) <= prec) break   # precision reached

  if (pBE > x) upper <- x.new       # move upper limit downwards

  if (pBE < x) lower <- x.new       # move lower limit upwards

  delta <- upper - lower            # new interval

}

if (print) cat("run-time:", round((proc.time()[3]-ptm[3]), 1),

               "seconds  iterations:", iter, "\n")

cat("regulator:", reg, " CV:", CV, " n:", n, " design:", des,

    "\ntarget alpha:", x, " adjusted alpha:", x.new,

    " pBE:", pBE, "(empiric alpha)\n")

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

‘alpha’ of scaled ABE? d_labes 2013-03-15 15:56
- ‘alpha’ of scaled ABE? Helmut 2013-03-15 17:27
  - ’alpha’ of scaled ABE: design d_labes 2013-03-16 20:10
    - N=24, 48 d_labes 2013-03-18 08:11
      - adaptive design without adjustment martin 2013-03-25 20:47
        
        α adjustment? Helmut 2013-03-26 15:21
        
        iteratively adjusted alpha martin 2013-03-26 16:19
        
        throw away our sample size tables? Helmut 2013-03-26 18:02
        
        if real martin 2013-03-26 19:44
        
        regulators don’t care? Helmut 2013-03-26 21:18
        
        adjusting α Helmut 2013-08-11 16:19
        
        missing letter apapanas 2024-10-31 06:02
        
        PowerTOST: sampleN.scABEL.ad() Helmut 2024-10-31 08:41
        
        PowerTOST: sampleN.scABEL.ad() apapanas 2024-11-08 10:48
        
        Molins et al. (2017) Helmut 2024-11-08 14:34
        
        target α in sim’s? Helmut 2013-03-27 15:38
        
        target α in sim’s? martin 2013-03-27 16:36
        
        If it is real: resultsHelmut 2013-03-28 23:20
        
        having alpha martin 2013-03-28 15:08
        
        fixed swr Helmut 2013-03-28 23:34
        
        fixed swr martin 2013-03-29 15:07
        
        Yes but no but yes but no but… Helmut 2013-03-29 16:10