Educate the IEC and regulators [Power / Sample Size]

posted by Helmut Homepage – Vienna, Austria, 2017-12-28 12:30 (2254 d 11:04 ago) – Posting: # 18111
Views: 32,938

Hi Yura,

❝ You are considering the power after the study at n = 28 (which were calculated before the study: GMR=0.95, CV=0.25, β=0.80). The question is whether it is possible to carry out a study at n = 50 and will this be forced bioequivalence?

As I wrote above the IEC and the authority should judge this before the study is done. I agree that in many cases the statistical knowledge of IECs is limited. However, once the protocol was approved by both, I don’t see a reason to talk about “forced BE” any more.

BTW, I don’t see a problem if a study is designed for 90% power (80% is not carved in stone). Let’s assume a dropout rate of 15% and we will already end up with 46 subjects:

CV     <- 0.25 # CV-intra
theta0 <- 0.95 # T/R-ratio
target <- 0.90 # desired (target) power
dor    <- 15   # expected dropout rate in percent
n      <- sampleN.TOST(CV=CV, theta0=theta0, targetpower=target,
                       print=FALSE)[["Sample size"]]
ceiling(n/(1-dor/100)/2)*2 # round up to next even

Considering your example and assuming that the GMR and CV turn out exactly as assumed, no dropouts (n=50): The 90% CI will be 87.47–103.18%. Fine with me. Not even a significant difference (100% included). If the drop­out-rate is as expected (n=38) the 90% CI will be 86.36–104.51%. If the assessor is not happy with that, he should have a chat with his colleague who approved the protocol and enlighten him about potential “over-powering” in study planing.
According to all guidelines (CI within the acceptance range) I can’t imagine a justification to reject the study. If the study is not accepted only due to the high sample size in the EEA the applicant might go for a referral (with extremely high chances of success) and in the USA the FDA will be sued right away. :-D

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz

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

Complete thread:

UA Flag
 Admin contact
22,916 posts in 4,807 threads, 1,646 registered users;
46 visitors (0 registered, 46 guests [including 12 identified bots]).
Forum time: 23:35 CET (Europe/Vienna)

Nothing shocks me. I’m a scientist.    Harrison Ford (as Indiana Jones)

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