Bioequivalence and Bioavailability Forum • Sample size for PK linearity

Sample size for PK linearity [Power / Sample Size]

posted by mjons – Sweden, 2011-12-08 19:03 (5317 d 23:14 ago) – Posting: # 7768
Views: 20,507

Hi,

Being new to dose proportionality studies, I am struggling with preparing a protocol for such a study. (Please excuse any stupid questions…) Since it should be a fairly common study to perform, it is strange there seems to be no consensus on how to do it properly. To just test if b≠1 seems illogical since this would favour an underpowered study.

A CI approach and acceptance criteria seems to be a more logical approach to me if you want to show that b is sufficiently close to 1. I found another paper by Smith (2000) and liked the power model approach suggested there, since you get a lot of (seemingly?) useful data out of this:

Possibility to claim dose proportionality (rather than just concluding that dose proportionality could not be rejected).
Even if failed (not demonstrated over the whole range) you get this rho-parameter with which you could potentially conclude a smaller interval that is dose proportional. (Or indicate dose proportionality over an even wider range...)

My questions with regards to this are:

Did I understand this correctly?
What are the pros and cons with this approach compared to other approaches? (What did I miss...?, Which method would you recommend?)
Should you just use the standard BE interval, 0.8000 to 1.2500 to calculate the acceptance interval (eq. 4) or could you expand it further?
Would a 90% CI for b be appropriate to test against the acceptance interval?

Best regards,
/Martin

Complete thread:

Sample size for PK linearity Kro 2009-05-19 10:56
- Sample size for PK linearity Helmut 2009-05-19 13:19
  - Sample size for PK linearity Kro 2009-05-19 13:56
    - Sample size for PK linearity Helmut 2009-05-19 15:09
      - Sample size for PK linearity ElMaestro 2009-05-26 17:26
        
        Weighting scheme Helmut 2009-05-26 19:52
      - Sample size for PK linearitymjons 2011-12-08 18:03
      - Sample size for PK linearity Lucas 2014-09-11 21:41
        
        Sample size for PK linearity - power model d_labes 2014-09-12 15:01
        
        Power dose proportionality - power model - Correction d_labes 2014-10-01 09:09
        
        Sample size for PK linearity d_labes 2014-09-13 15:05
        
        Sample size for PK linearity Lucas 2014-10-13 20:36
        
        Sample size for PK linearity d_labes 2014-10-14 09:26
        
        Sample size for PK linearity Lucas 2014-10-14 15:24
  - dose proportionality vs. dose linearity martin 2009-05-25 08:46
    - dose proportionality vs. dose linearity Helmut 2009-05-25 14:59