Slightly off-topic: The wonders of pilot trials [Study As­sess­ment]

posted by ElMaestro  – Denmark, 2013-07-29 11:19 (4717 d 01:48 ago) – Posting: # 11095
Views: 25,135

Hi Sam and all,

I think this is extremely interesting:

❝ Fed Pilot Study Results (Total Sample szie 18):

❝ Dependent      Ratio[%Ref] CI_90_Lower CI_90_Upper Power   CV(%)  n

❝ Ln(AUCINF_obs)     87.39     69.74      108.72      51.0   32.2  14

❝ Ln(AUClast)        81.09     67.57       97.32      65.0   26.3  14

❝ Ln(Cmax)           87.07     67.52      113.11      41.0   37.8  14

❝

❝ Fed Pivotal Study Results (Total Sample szie 48):

❝ Dependent      Ratio[%Ref] CI_90_Lower CI_90_Upper Power   CV(%)  n

❝ Ln(AUCINF_obs)     96.45     91.53      101.64     100.0   14.5  44

❝ Ln(AUClast)        95.94     90.95      101.21     100.0   14.8  44

❝ Ln(Cmax)           87.91     81.81       94.47      99.99  20.3  44


Note that the upper CI limit for ln(AUCt) is about 97% and PE=81% in the pilot trial and in the pivotal trial the PE comes out at 96%. This shows the practical importance of not trusting too much in pilot trials. In this case, however, it worked in the sponsor's favour.

I think I will mention this example at the IPAC-RS meeting in Orlando in March 2014 where the talk is about two-stage approaches. This story could perhaps exemplify why a two-stage trial with a stopping criterion would have been a potentially interesting alternative.

At this point, however, I am slightly confused:
  1. How did you transit from the pilot trial to the pivotal?
    It looks like you aimed for N=48 in the pivotal, and got N=44 evaluable subjects. But how did N=48 enter the scene?
    With the CV for Cmax being 37.8, and assuming this is a 2,2,2-BE trial (is it not?), N=48 gives a very low power at PE=87.07; if optimism prevails and we think the PE is actually 95% then I get a power of around 71% for N=48; it would need to be N=60 to get 80% power.
  2. Could you tell how much time was in between the pilot and the pivotal fed studies?
Highly, highly interesting this story. And garnished with a classical Hötzi rant, it has truly made my day. :-D
—
Pass or fail!
ElMaestro

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