Inflation type one error: FDA [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2019-11-10 11:33  – Posting: # 20780
Views: 73

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
 Mix view
Bioequivalence and Bioavailability Forum |  Admin contact
19,963 posts in 4,226 threads, 1,373 registered users;
online 12 (1 registered, 11 guests [including 10 identified bots]).
Forum time (Europe/Vienna): 21:06 CET

There are no dangerous thoughts;
thinking itself is dangerous.    Hannah Arendt

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
HTML5