Bioequivalence and Bioavailability Forum • Subjects in replicate BE study EU/FDA

Subjects in replicate BE study EU/FDA [RSABE / ABEL]

posted by Shuanghe – Spain, 2015-01-08 12:08 (3665 d 21:11 ago) – Posting: # 14252
Views: 29,716

Hi all,

If I can generalise the question in original post to "Subjects to be considered in replicate BE study in EU/FDA submission" to avoid a new post.

For 3-period partial replicate BE I did the same thing as mentioned by Detlew.
To state it briefly:

samples from subjects who complete at least 2 periods will be analysed
subjects who has 2 periods of R will be included to determine Swr
subject who can provided at least one T and one R will be included for BE evaluation

The last 2 is "done automatically" as Detlew said but I would prefer to state it very clearly in the protocol just in case. ;-)

For 4-period full replicate BE for FDA submission, what I did is the following and I'd appreciate any comments:

samples from subjects who complete at least 2 periods with at least one R will be analysed (e.g., subject with 0T+2R, 1T+1R, 1T+2R, 2T+1R, 2T+2R. in fact all combinations except 2T+0R)
subject who has at least 2 Rs will be used to estimate Swr to determine if scaled approach is applicable or not.
for scaled approach, only subject who complete all 4 periods will be included for BE evaluation
if Swr is less than the criterion for scaled approach then average BE approach will be used and all subject who can provide at least 1T and 1R will be included for BE evaluation.

For the first point, it seems there's no point to included subject without any data of R. What's your thought?

The 2nd and 3rd points are answers from FDA.

In one of the original questions I suggested to modify their code to included subjects with 1T2R, 2T1R etc but they stress that only subjects with 4 periods should be included for BE but all subject with 2R, even without any T, should be used for Swr. So the code is too sacred to be changed. :-D

The last point is a recent addition (as I forgot to ask FDA years ago) from one replicate study that happened to have high dropout rate (missing 1 or 2 periods) but ISCV of one PK parameter is less than the HVDP criterion so no scaled approach for that parameter. But the protocol didn't have the point 4 so only subjects with 4 periods were included and the power is sh** due to few subjects we have!
so any suggestions on this point?

For EU it seems much easier as the sample data set in the PK Q/A document has some missing periods (but all have at least 1T and 1R).

—
All the best,
Shuanghe

Complete thread:

Statistical Analysis section of partial replicate BE study cher0424 2015-01-07 06:39 [RSABE / ABEL]
- Subjects to be considered in partial replicate BE study d_labes 2015-01-07 14:45
  - Subjects to be considered in partial replicate BE study cher0424 2015-01-07 15:35
  - Subjects to be considered in partial replicate BE study cher0424 2015-01-08 06:28
    - Subjects to be considered in partial replicate BE study d_labes 2015-01-08 09:03
      - Subjects to be considered in partial replicate BE study cher0424 2015-01-08 09:51
        
        Subjects to be considered in partial replicate BE study d_labes 2015-01-08 10:27
        
        Subjects in replicate BE study EU/FDAShuanghe 2015-01-08 11:08
        
        Subjects in replicate BE study EU/FDA cher0424 2015-01-08 13:56
        Subjects in replicate BE study EU/FDA Relaxation 2015-03-02 09:46
        
        Subjects in replicate BE study EU/FDA d_labes 2015-03-02 11:38
        Subjects in replicate BE study EU mittyri 2015-03-19 20:12
  - Subjects to be considered in partial replicate BE study Dr_Dan 2015-01-08 08:59
    - Subjects to be considered in partial replicate BE study d_labes 2015-01-08 09:04
      - Subjects to be considered in partial replicate BE study Astea 2015-03-01 18:12
        
        Subjects to be considered in partial replicate BE study yjlee168 2015-03-01 19:01
        
        Subjects to be considered in partial replicate BE study Astea 2015-03-09 14:43
        
        NCA with bear? yjlee168 2015-03-09 15:24
        
        Bear and null PK parameters mittyri 2015-03-25 09:50
        
        to exclude or not to exclude the subjects with bear? yjlee168 2015-03-28 21:03
        
        to exclude or not to exclude - let the user decide mittyri 2015-03-29 19:04
        
        to exclude or not to exclude - let the user decide yjlee168 2015-03-30 11:28
        
        to exclude or not to exclude - let the user decide ElMaestro 2015-03-30 15:44
        
        to exclude or not to exclude - let the user decide yjlee168 2015-03-31 11:15
        
        Constraints, algebra, jommetry and such ElMaestro 2015-03-31 12:16
        
        Constraints, algebra, jommetry and such yjlee168 2015-03-31 13:13
        
        Constraints, algebra, jommetry and such ElMaestro 2015-03-31 14:26
        
        Constraints, algebra, jommetry and such mittyri 2015-04-01 08:25
        
        Proc GLM, lm() do not auto-exclude subjects d_labes 2015-04-01 09:15
        
        Proc GLM, lm() do not auto-exclude subjects ElMaestro 2015-04-01 16:29