Bioequivalence and Bioavailability Forum

AUCextrap more than 20% [Study Assessment]

posted by sam – India, 2013-08-01 14:55 (4710 d 09:53 ago) – Posting: # 11146
Views: 30,908

Hi Helmut,

Thanks for your valuable suggestions:

❝ • You are right about FDA’s thinking about ‘outliers’. BTW, did these two subjects really qualify by a statistical test or was your criterion >20% res. AUC?

In my study there were five subjects whose data for the test products are not in concurrence to the other subjects data. After thorough review we applied test of outlier and among the five subjects two qualifies as outliers. Among the two outliers one subject has AUCextrap value more than 20% and other subject’s whose extrapolation value is more than 20% is among the five whose data are aberrant compared to the other subjects data.

❝ • You can try to start an argument based on the fact that the formulation was ER. In BE we are interested in comparing the absorption (= formulation + drug specific) not distribution/elimination (= drug specific). With ER the slowest phase might be absorption – not elimination. This is true once you crossed flip-flop PK (k_a = k_el). Even for k_a > k_el the apparent (!) elimination will be contaminated by absorption. Compare half lives of your study with literature data of immediate release formulations. Likely your half lives are longer. Therefore, AUC_∞ is a more relevant metric for extent of absorption than AUC_t.

Should I remove the AUCt parameter only for that subjects which have AUCextrap value more than 20% and write a comment on the report as per our suggestions.

❝ • Your sample size was terribly high given the CVs of 25–27%.

Since the ratio in the pilot study was around 84% and considering the ISCV of around 26%. The actual sample size come to be around 138.

Best Regards
Sam

Edit: Standard quotes restored. [Helmut]

Complete thread:

AUCextrap more than 20% sam 2013-08-01 06:15
- AUCextrap more than 20% ElMaestro 2013-08-01 10:29
  - AUCextrap more than 20% sam 2013-08-01 11:21
    - AUCextrap more than 20% ElMaestro 2013-08-01 11:39
      - AUCextrap more than 20% sam 2013-08-01 12:01
        
        AUCextrap more than 20% Helmut 2013-08-01 12:52
    - forced BE d_labes 2013-08-01 11:59
      - Gambling ♠ ♣ ♥ ♦ Helmut 2013-08-01 13:31
- AUCextrap more than 20% Helmut 2013-08-01 12:32
  - AUCextrap more than 20%sam 2013-08-01 12:55
    - 46% power in study planning? Helmut 2013-08-01 13:18
      - 46% power in study planning? sam 2013-08-01 13:40
        
        46% power in study planning? jag009 2013-08-01 20:04
        
        Re-dosing Helmut 2013-08-02 03:32
        
        Re-dosing jag009 2013-08-02 05:10
        
        Re-dosing Helmut 2013-08-02 14:44
        
        46% power in study planning? sam 2013-08-02 07:00
        
        Carved in stone? Helmut 2013-08-02 03:22
        
        Carved in stone? sam 2013-08-02 07:02
        
        Carved in stone? luvblooms 2013-08-02 08:37
        
        Carved in stone? sam 2013-08-02 09:01
        
        Ethics (again) Helmut 2013-08-02 14:53
        
        Update jag009 2013-08-02 17:25
        
        Update Helmut 2013-08-02 18:11
        
        Update jag009 2013-08-02 20:11
        
        Outliers (CAN) Helmut 2013-08-02 20:56
        
        Outliers (CAN) jag009 2013-08-02 22:23
        
        OT: Expert Helmut 2013-08-03 10:11
        
        Update jag009 2013-08-02 22:29
        
        Update ElMaestro 2013-08-02 23:08
        
        Update jag009 2013-08-03 23:00
        
        Update luvblooms 2013-08-05 06:02
        
        Update jag009 2013-08-05 20:14

AUCextrap more than 20% [Study As­sess­ment]

Complete thread:

AUCextrap more than 20% [Study Assessment]