Bioequivalence and Bioavailability Forum • Common variance!

Common variance! [Design Issues]

posted by jag009 – NJ, 2012-06-11 19:25 (5122 d 04:23 ago) – Posting: # 8685
Views: 11,247

Hi Helmut,

❝ Right. But there’s another problem: In this type of higher-order XOver you obtain a common (pooled) variance from treatment variances. What if one of the formulations not only shows a PE far away from 100% (which would lead to dropping it from development), but performs ‘bad’ in terms of the CV? Especially if MR formulations are concerned, the differences sometimes are large. This formulation will inflate your CIs and require a larger sample size compared to simple XOvers. We had a similar debate in the EU where EMA in their drafted GL wanted to see a four-way XOver T and R (fed/fasting). In the final GL such a design is not required.

Agreed. I forgot to say that a larger sample size will also serve to compensate for the widening of the CIs due to potential increase in variations due to formulation performance differences. Now how much of an increase in sample size is the problem... Like you said we don't know how bad 1 or 2 out of the 3 test formulations will perform.

Complete thread:

Curiosity: Running BE studies with more than 2 arms jag009 2012-06-11 15:01
- Common variance! Helmut 2012-06-11 16:23
  - Common variance!jag009 2012-06-11 17:25
    - Common variance! Helmut 2012-06-11 17:35
      - Common variance! jag009 2012-06-11 20:03
        
        Common variance! ElMaestro 2012-06-11 20:34
        
        Common variance! Helmut 2012-06-12 01:03
        
        Common variance! ElMaestro 2012-06-12 13:22
  - Common variance! jag009 2012-06-12 19:56
    - What if I run a study with 2 references? jag009 2012-06-12 20:00
    - Common variance! Helmut 2012-06-12 20:39
      - Two References d_labes 2012-06-13 09:11
        
        Two References jag009 2012-09-10 22:48
        
        Two treatments only d_labes 2012-09-11 08:20
  - Common variance! jag009 2012-06-13 16:08