Bioequivalence and Bioavailability Forum

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posted by Helmut – Vienna, Austria, 2016-05-12 16:34 (2899 d 07:40 ago) – Posting: # 16299
Views: 31,110

Hi Angus,

❝ We have completed a dose proportionality study using the lowest strength to the highest strength of a modified release formulation of a class I drug. The approach used was the usual cross-over design with 20 subjects (AB, BA) and dose normalized the PK parameters Cmax and AUC0-T prior to bioequivalence. No problem we are BE comfortably within the limits (0.8-1.25).

Testing only two levels for dose proportionality is somewhat unconventional.

❝ Another worker has used the power model with the same data set for dose proportionality […]

Does it look like this (high dose = 8× low dose)?

[image]

❝ The point estimates are much the same as my approach, […]

Numbers? AUC only – C_max is of limited value in DP.

❝ […] but he quotes 98% CI.

Smells of Bonferroni’s adjustment for four simultaneous (and independent) tests in order to control the familywise error rate: 100(1–2α/4) = 97.5% CI and FWER 1–(1–α)⁴ = 0.0491.
In the power model we have only two parameters (the coefficient α and the exponent β: E[D] = α·D^β (independent from the number of dose levels tested) and we are interested only in β. I don’t see why a multiplicity-adjustment was done.

❝ His CI values are also within the lmits.

How did he get a CI of β? With two dose levels we have zero degrees of freedom for a model with two parameters.

Before we can discuss variances, we need more information.

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Helmut Schütz

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Complete thread:

Dose Proportionality and Variance AngusMcLean 2016-05-11 16:55
- More information, pleaseHelmut 2016-05-12 14:34
  - More information, please AngusMcLean 2016-05-13 16:40
    - Setup in Phoenix/WinNonlin Helmut 2016-05-14 02:26
      - Setup in Phoenix/WinNonlin AngusMcLean 2016-05-14 18:54
        
        Setup in Phoenix/WinNonlin Helmut 2016-05-15 14:47
        
        Setup in Phoenix/WinNonlin AngusMcLean 2016-05-15 15:17
        
        Phoenix 64 Warning Helmut 2016-05-15 15:56
        
        Phoenix 64 Warning AngusMcLean 2016-05-15 20:11
        
        OT: imperial vs. metric units Helmut 2016-05-16 16:26
        
        Setup in Phoenix/WinNonlin ElMaestro 2016-05-15 20:54
        
        Setup in Phoenix/WinNonlin AngusMcLean 2016-05-15 22:30
      - Setup in Phoenix/WinNonlin AngusMcLean 2016-05-16 21:00
        
        NCSS vs. PHX/WNL vs. SAS Helmut 2016-05-17 01:50
        
        NCSS vs. PHX/WNL vs. SAS - Validation? mittyri 2016-05-18 08:23
        
        Diagnostics ElMaestro 2016-05-18 09:20
        
        Diagnostics: R and Phoenix Helmut 2016-05-18 15:14
        
        Diagnostics: R zizou 2016-05-22 19:07
        
        Diagnostics: R Helmut 2016-05-23 01:22
        
        SASian potpourri d_labes 2016-05-24 12:02
        
        Compilation Helmut 2016-05-24 14:27
        
        REML or not d_labes 2016-05-24 16:33
        
        complete or not Helmut 2016-05-24 16:57
        
        Compilation AngusMcLean 2016-05-26 16:46
        
        doubts about NCSS Helmut 2016-05-26 19:13
        
        Doubts about NCSS zizou 2016-05-26 23:38
        
        Compilation AngusMcLean 2016-05-28 00:51
        
        Kenward-Roger? Helmut 2016-05-28 15:59
        
        90% confidence interval for R_dnm Shuanghe 2019-01-04 17:45
        
        90% confidence interval for R_dnm d_labes 2019-01-05 14:01
        
        Visualizing lmer and limits mittyri 2019-01-06 17:00
        
        Visualizing lmer and limits Shuanghe 2019-01-07 11:05
        Visualizing lmer and limits d_labes 2019-01-07 15:08
        
        Visualizing lmer and limits mittyri 2019-01-13 23:53
        
        90% confidence interval for R_dnm Shuanghe 2019-01-07 10:53
        
        90% confidence interval for R_dnm d_labes 2019-01-07 15:17
        
        90% confidence interval for R_dnm Shuanghe 2019-01-07 17:11
        
        90% confidence interval for R_dnm d_labes 2019-01-07 18:24
        offtop: greek letters and tables mittyri 2019-01-08 00:19
        
        OT: greek letters and symbols Helmut 2019-02-02 16:04
        
        Smith’s paper Helmut 2016-05-18 14:44
        
        Smith’s paper d_labes 2019-01-05 15:00

More information, please [Study As­sess­ment]

Complete thread:

More information, please [Study Assessment]