New paper (method D for PE 0.90) [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2011-04-19 16:30 (5178 d 03:16 ago) – Posting: # 6921
Views: 26,458

Dear D. Labes,

❝ ❝ ... It might be possible to adjust the α level for methods B/C as well, but this has not been evaluated yet.

❝

❝ This sentence of the paper is confusing me somewhat :confused:.

❝ As far as I had understood the method D is a variant of method C with adjusted alpha level.


This sentence is my intepretation. B/C are based on Pocock’s 0.0294. You are right about method D. The original quote is:

Although methods B and C, with the assumed GMR of 0.95 for the estimation of power and second-stage sample size as described in our first paper, in our opinion, provide acceptable control of the Type I error rate, changing the assumed GMR from 0.95 to 0.90 with these methods results in excessive inflation of the Type I error rate under some circumstances, and should be avoided. It is possible that by adjusting the α levels (α spending function) Methods B and C could be modified so as to control the Type I error rate with an assumed GMR of 0.90, but that is beyond the scope of this investigation.


❝ Moreover I don't share the authors view of "excessive inflation of Type I error rate".


Of course the criterion the authors have set for an "acceptable" inflation (i.e., ≤5.2%) is arbitrary.

❝ In view of other Type I inflation allowed by the FDA, f.i. the inflation around CV=30% for the scaled ABE up to 6.5%-7% due to the regulatory sw0=0.25 (see this presentation, page 23) I would consider the inflations observed in the paper (max. 0.0547) marginal.


Me too. On the other hand, I’m not sure whether EMA cares about the FDA. :-D I talked to Barbara Davit last year about this issue and she said that simulations by Donald Schuirmann showed the contrary. But nothing is published and as a fan of the two Lászlós I have strong doubts. The GL states:

If this approach is adopted appropriate steps must be taken to preserve the overall type I error of the experiment and the stopping criteria should be clearly defined prior to the study.


Bonus questions:
  1. What is an acceptable inflation?
  2. There’s no stopping criterion in Potvin’s method. My protocols stated clearly that there is none in the method and were approved by the BfArM and two IECs. Experiences?

❝ What makes me also wondering is that the alpha "inflation" is shifted to higher stage 1 number of subjects if the variability increases. This is somehow counter-intuitive to me. Small is beautiful?


Yes, that’s strange.
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Complete thread:

UA Flag
Activity
 Admin contact
23,424 posts in 4,927 threads, 1,673 registered users;
45 visitors (0 registered, 45 guests [including 8 identified bots]).
Forum time: 19:47 CEST (Europe/Vienna)

Medical researches can be divided into two sorts:
those who think that meta is better and those
who believe that pooling is fooling.    Stephen Senn

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