Dropouts continued [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2017-09-19 17:17  – Posting: # 17819
Views: 3,325

Hi ElMaestro,

had a closer look into the loss of power due to dropouts.

» Let us say we look at e.g. CV=.3 and N1=12 (6 per sequence at stage 1). What would you expect in terms of power […], if 2 subjects go lost in sequence RT during stage 2?
»
» […] stage 2's are often (not always, just often in practice) much larger than stage 1's…

Larger is OK but too large isn’t. With the exception of Xu’s methods (my current favorite) you don’t reach the target power with small n1. ‘Potvin B’:

                   power
n1  N (median) stage 1 final
12      44      0.0671 0.784
14      44      0.104  0.799
16      44      0.155  0.810
24      36      0.413  0.830
30      30      0.566  0.834

In your example final power is 78.4%, 93.1% of studies proceed to the second stage, and the median total sample size is 44. Let’s add dropouts and see what happens to power.

 N  power
44  0.779
43  0.768
42  0.757
41  0.745
40  0.733

If n1 is small you are punished twice: You don’t reach the target power and the total sample sizes will be larger.
My current practice is to use n1 which is ~75–80% of the fixed sample design with a ‘best-guess’ CV. With n1 30 we exceed the target power with 83.4%, only 41.8% studies proceed to the second stage (i.e., you have a 56.6% chance to show BE already in the first), and the median total sample size is 30 (!). OK, the mean is 39… The distribution looks like that:

[image]


Even with a futility (Nmax 64) final power is with 77.6% close to the target but power in the first stage is still 56.6%. With a futility on the total sample size you can not only ease the sponsor but – hopefully – the BSWP. The Type I Error drops from 0.0440 to 0.0427.

I don’t like small first stages.

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
20,128 posts in 4,245 threads, 1,384 registered users;
online 4 (0 registered, 4 guests [including 2 identified bots]).
Forum time (Europe/Vienna): 23:14 CET

You really don’t know what you don’t know until you write about it.
Then, everyone knows what you don’t know.    Rod Machado

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