Bioequivalence and Bioavailability Forum • Validation of FDA's RSABE on NTIDs

Validation of FDA's RSABE on NTIDs [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2017-08-23 17:00 (2223 d 08:13 ago) – Posting: # 17744
Views: 14,989

Hi Zhang Yong,

❝ But from the formula in the guidance (page 4, line 5) with Alpha=0.1, I guess the guidance is right, it calulates 90% CI of Swt/Swr, but not 95% CI.

❝ Need your clarification? or FDA is wrong?

The FDA is never wrong. But so am I. :-D

The guidance asks to calculate an confidence interval but only the upper confidence limit is assessed. Simply: The 90% CI has an upper and lower 95% CL.

❝ ❝ Personally I would prefer […] to run a mixed effects model with restricted maximum likelihood…

❝ ❝ I got: CV_wR 15.86% and CV_wT 5.73%. Interesting.

❝

❝ I guess your result of 15.86% and 5.73% are obtain from the sheet of "Final Variance Parameters" from ABE results using PHX WNL.

Correct.

❝ Here the CVwr and CVwt are different from those calculated from Swr and Swt.

❝ I prefer the result calculated from Swr and Swt.

❝ What's your opinion?

For my preferences see above. If you have to follow the guidance that’s not an option.

BTW, if you have Phoenix WinNonlin why bother fiddling around in Excel? I have some doubts whether an agency will accept that. At least the EMA wouldn’t. Quoting the Q&A document:

3.3. Alternative computer programs
[…] Results obtained by alternative, validated statistical programs are also acceptable except spreadsheets because outputs of spreadsheets are not suitable for secondary assessment.

BTW, Certara is working on a validated template for PHX WNL and it will be published in the near future.

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Helmut Schütz

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Complete thread:

Validation of FDA's RSABE on NTIDs yicaoting 2017-08-22 18:01 [RSABE / ABEL]
- Validation of FDA's RSABE on NTIDs Helmut 2017-08-22 20:25
  - Validation of FDA's RSABE on NTIDs yicaoting 2017-08-23 05:30
    - Validation of FDA's RSABE on NTIDsHelmut 2017-08-23 15:00
      - Validation of FDA's RSABE on NTIDs yicaoting 2017-08-30 14:33
        
        Validation of FDA's RSABE on NTIDs Helmut 2017-08-30 15:04
  - Clarification needed: Validation of FDA's RSABE on NTIDs CECIF 2018-02-19 22:20
    - FDA's RSABE on NTIDs in R d_labes 2018-02-20 14:10
      - FDA's RSABE on NTIDs in R CECIF 2018-03-01 21:08
        
        FDA's RSABE on NTIDs in R Helmut 2018-03-01 23:39