Bioequivalence and Bioavailability Forum

Problems resolved? [Study Performance]

posted by Helmut – Vienna, Austria, 2014-06-11 04:01 (3973 d 09:25 ago) – Posting: # 13057
Views: 18,403

Hi Khaoula!

❝ […] I havnt randomisation because they dont give me it, they asked me to try to understand where is the error, […]

May I ask: Who are “they”?

❝ […] our design is't appropriate (must have replicate design), […]

Not necessarily. Only if you want to widen the acceptance range (EMA) or go with reference-scaling (FDA). But if CV_WR <30% scaling is not allowed.

❝ […] the problem of our study is number of subject, […]

Mainly. If we assume the T/R-ratio and CV “as carved in stone” – which I would not recommend anyway – you would have needed the following sample sizes in order to demonstrate BE with 80% power:

design  method                     sample size

2×2×2   unscaled (80–125%)            630

2x2×3   fully replicated unscaled     472

2×2×4   fully replicated unscaled     316

2x2x3   scaled (EMA)                  474

2×2×4   scaled (EMA)                  316

2x2x3   scaled (FDA)                  474

2×2×4   scaled (FDA)                  318

Note that reference-scaling would not help with such a low CV.

You have a lot of problems arising from the study:

The T/R-ratio of 121% is close to the upper limit of the acceptance range. Since the confidence interval (104.22%, 140.53%) does not include 100%, formulations are significantly different (p 0.04155). Is there an end of bugs in Kinetica? Despite the – wrong! – CI does also not include 100%, formulations are considered not significantly different (p 0.05391). Amazing.
With such a large deviation from the reference any attempt to show BE in a larger study is not ethical, IMHO.
The CV is untypically low for omeprazole’s C_max. Maybe you were just lucky. But luck is not what you should expect for the next study.

❝ the test drug is really bioequivalent of réference, […]

Why do you think so? You would need hundreds of subjects to squeeze the CI within the acceptance range.

❝ this study was done to learn how to do biequivalennce study

Can you briefly summarize what you have learned?

A drug is that substance which, when injected into a rat,
   will produce a scientific report.    Anonymous

Pharmacokinetics: one of the magic arts of divination
   whereby needles are stuck into dummies in an attempt
   to predict profits.    Stephen Senn

❝ I calculated CV with error = 0.0471261 and I had CV% = 100√(ℯ^0.0471261 – 1) = 21.97% but I thought that I was wrong

So instead of following a formula given in numerous papers and textbooks you rather trusted in the output of a piece of software?

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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

Complete thread:

randomization khaoula 2014-06-06 14:04 [Study Performance]
- Imbalanced cross-overs Helmut 2014-06-06 14:47
  - Imbalanced cross-overs khaoula 2014-06-06 16:03
    - CV 0.03%? Helmut 2014-06-07 13:52
    - Imbalanced cross-overs jag009 2014-06-09 15:36
      - Imbalanced cross-overs khaoula 2014-06-09 22:07
        
        Bag full of bugs Helmut 2014-06-10 00:37
        
        Randomisation? ElMaestro 2014-06-10 01:00
        
        Randomisation? Helmut 2014-06-10 14:53
        
        Randomisation? khaoula 2014-06-11 00:17
        
        Problems resolved?Helmut 2014-06-11 02:01
        
        Problems resolved? khaoula 2014-07-24 13:36
        
        corrected data in PHX/WNL Helmut 2014-07-27 01:37
        
        Which version of Kinetica? Helmut 2014-06-11 19:51
        
        Which version of Kinetica? khaoula 2014-06-12 00:41
        Which version of Kinetica? khaoula 2014-07-25 00:49
        
        adjusted means (aka LSMs) Helmut 2014-07-27 02:23
        
        adjusted means (aka LSMs) khaoula 2014-08-25 21:41

Problems resolved? [Study Per­for­mance]

Complete thread:

Problems resolved? [Study Performance]