More information, please [Study Assessment]
❝ 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)?
❝ The point estimates are much the same as my approach, […]
Numbers? AUC only – Cmax 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.
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Dose Proportionality and Variance AngusMcLean 2016-05-11 16:55 [Study Assessment]
- 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
- Phoenix 64 Warning AngusMcLean 2016-05-15 20:11
- Setup in Phoenix/WinNonlin ElMaestro 2016-05-15 20:54
- Setup in Phoenix/WinNonlin AngusMcLean 2016-05-15 22:30
- Phoenix 64 Warning Helmut 2016-05-15 15:56
- Setup in Phoenix/WinNonlin AngusMcLean 2016-05-15 15:17
- Setup in Phoenix/WinNonlin Helmut 2016-05-15 14:47
- 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
- doubts about NCSS Helmut 2016-05-26 19:13
- 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
- 90% confidence interval for R_dnm Shuanghe 2019-01-07 17:11
- 90% confidence interval for R_dnm d_labes 2019-01-07 15:17
- Visualizing lmer and limits mittyri 2019-01-06 17:00
- 90% confidence interval for R_dnm d_labes 2019-01-05 14:01
- REML or not d_labes 2016-05-24 16:33
- Compilation Helmut 2016-05-24 14:27
- SASian potpourri d_labes 2016-05-24 12:02
- Diagnostics: R Helmut 2016-05-23 01:22
- Diagnostics: R zizou 2016-05-22 19:07
- Diagnostics: R and Phoenix Helmut 2016-05-18 15:14
- Smith’s paper Helmut 2016-05-18 14:44
- Smith’s paper d_labes 2019-01-05 15:00
- Diagnostics ElMaestro 2016-05-18 09:20
- NCSS vs. PHX/WNL vs. SAS - Validation? mittyri 2016-05-18 08:23
- NCSS vs. PHX/WNL vs. SAS Helmut 2016-05-17 01:50
- Setup in Phoenix/WinNonlin AngusMcLean 2016-05-14 18:54
- Setup in Phoenix/WinNonlin Helmut 2016-05-14 02:26
- More information, please AngusMcLean 2016-05-13 16:40
- More information, pleaseHelmut 2016-05-12 14:34