Inflation type one error: FDA [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2019-11-10 11:33  – Posting: # 20780
Views: 579

Hi Mikalai,

» […] what regulators say on this subject? I do not remember any reflection on this matter in official documents (EMA, FDA)?

Some slides of Terry Hyslop (Director, Division of Biostatistics) of his presentation “Bioequivalence (BE) for Highly Variable Drugs” at the AAPS Workshop (New Orleans, Nov 2010) – after the progesterone guidance was published…


[image]

[image]
Aka the ‘implied limits’ (see this post and slide 23 below).

[image]

[image]
Well roared, lion! Trouble starts because we use \(s_{WR}\) instead of the unknown \(\sigma_{WR}\).
Nasty but \(s_{WR}\) is all we have.
Typo, should read
… use scaled average BE if sWR > cutoff.

[image]

[image]
Illegible text (white with grey shadowing):
  assuming no subject-by-formulation interaction, σWT = σWR,
  true GMR = max (1.25, implied scaled BE limit)

[image]

[image]


Check:

library(PowerTOST)
res        <- data.frame(method = c("ABE", "RSABE"), TIE = NA)
res$TIE[1] <- power.TOST(CV = 0.3, n = 36, theta0 = 1.25,
                         design ="2x3x3")
res$TIE[2] <- power.RSABE(CV = 0.3, n = 36, theta0 = 1.25,
                          design ="2x3x3", nsims = 1e6)
res$TIE    <- signif(res$TIE, 4)
print(res, row.names = FALSE)

# method    TIE
#    ABE
0.0500
#  RSABE 0.1323


Hence, the FDA was well aware of the inflated type I error and decided to ignore it.

Cheers,
Helmut Schütz
[image]

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

Complete thread:

Activity
 Admin contact
20,346 posts in 4,274 threads, 1,404 registered users;
online 14 (0 registered, 14 guests [including 3 identified bots]).
Forum time (Europe/Vienna): 15:47 CET

Any one who considers arithmetical methods
of producing random digits is, of course,
in a state of sin.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5