Bioequivalence and Bioavailability Forum

Main page Policy/Terms of Use Abbreviations Latest Posts

 Log-in |  Register |  Search

Back to the forum  Query: 2018-05-25 09:10 CEST (UTC+2h)
 
nobody
Senior

2018-02-27 19:02

Posting: # 18472
Views: 926
 

 Shorter sampling interval in pilot - Good idea? [Design Issues]

Hy!

Have a drug with "normal" half-life of some hours in the mean, but considerable variability (BOTH target params). So pilot will be huuuugh and fully replicate (planned: EU submission).

Sponsor wants to make a little cheaper by having only 24 h sampling in the pilot, but considerably longer in the pivotal trial.

Good idea? Regarding sample size estimation for the pivotal (including adjusted acceptance range for Cmax, but standard acceptance range for AUC...).

Any thoughts or numbers? :-)

Οὐδείς

Kindest regards, nobody
ElMaestro
Hero

Denmark,
2018-02-27 21:42

@ nobody
Posting: # 18473
Views: 786
 

 Shorter sampling interval in pilot - Good idea?

Hy yourself,

» Sponsor wants to make a little cheaper by having only 24 h sampling in the pilot, but considerably longer in the pivotal trial.
»
» Good idea? Regarding sample size estimation for the pivotal (including adjusted acceptance range for Cmax, but standard acceptance range for AUC...).

That's likely going to be fine. It will regularly be Cmax that is the showstopper. Even if your AUC does not cover 80% and if you are not sampling to 72hrs, then the idea you get about AUC aspects will still be very qualified.

Note one thing which is commonly misunderstood: When pilot trials have small sample sizes compared to pivotal studies (which is almost a definition) then they do not give good info about formulation matches in BE (or, where applicable, of superiority prospects, but this is often very dependent of placebo arms).
Pilot BE studies are great for everything but screening for formulation matches.:-)

“A ten-year, double-blind study from the Mayo Clinic concluded that even in late stages of dementia, the last to go is the lobe of the brain in charge of cafeteria layout.” (Serge Storms/Tim Dorsey).


Best regards,
ElMaestro

- Bootstrapping is a relatively new hobby of mine. I am only 30 years late to the party.
nobody
Senior

2018-02-27 22:47

@ ElMaestro
Posting: # 18474
Views: 768
 

 Shorter sampling interval in pilot - Good idea?

Hi Iceland II

Sounds good. With highly variable Cmax point estimates are frequently jumping around like hell between studies, but with highly variable AUC the point estimate from pilot should be more reliable/less freakish (with a reasonably high n), right? Didn't have a look at the numbers recently...

Thanks for reply!

(-11.4°C right in front the window... still falling...)

Kindest regards, nobody
ElMaestro
Hero

Denmark,
2018-02-27 22:58

@ nobody
Posting: # 18475
Views: 755
 

 Shorter sampling interval in pilot - Good idea?

Hi Nobody,

it is quite simple.
Look at the pilot trial's CI for whatever you are interested in, such as the T/R.

If the CI is for example 60-149 (and it might well be in a pilot. Even for AUC. Even if AUC's CV is not high) then you cannot really take any decision based on the location of T/R. Think about it. For two identical product, you will "quite likely" make the wrong decision whether your decision is.

There was a weirdo who wrote a paper about pilot and repeat trials as development tools in BE. The author's only regret is that he presented the data the way he did. It would have appealed more to the broad audience if he had graphed the chance of taking the wrong decision in the various scenarios when the decision was to be based on the location of the apparent T/R.

“A ten-year, double-blind study from the Mayo Clinic concluded that even in late stages of dementia, the last to go is the lobe of the brain in charge of cafeteria layout.” (Serge Storms/Tim Dorsey).


Best regards,
ElMaestro

- Bootstrapping is a relatively new hobby of mine. I am only 30 years late to the party.
nobody
Senior

2018-02-28 08:36

@ ElMaestro
Posting: # 18477
Views: 725
 

 Shorter sampling interval in pilot - Good idea?

» There was a weirdo who wrote a paper about pilot and repeat trials as development tools in BE. The author's only regret is that he presented the data the way he did. It would have appealed more to the broad audience if he had graphed the chance of taking the wrong decision in the various scenarios when the decision was to be based on the location of the apparent T/R.

Yep, next time you send me your draft and we discuss the data presentation. :-D

GMR of AUC is of some interest to judge which formulation to take to the pivotal (one from pilot(s) or maybe something completely different?). Not so much for sample size. Would take 0.9 plus CVintra estimated for Test from pilot(s) and see where one ends (1 gazillion of HVs?)...

Kindest regards, nobody
Back to the forum Activity
 Thread view
Bioequivalence and Bioavailability Forum | Admin contact
18,290 posts in 3,889 threads, 1,169 registered users;
20 users online (0 registered, 20 guests).

The purpose of models is not to fit the data,
but to sharpen the questions.    Samuel Karlin

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
XHTML/CSS RSS Feed