Bioequivalence and Bioavailability Forum • FDA RSABE is ISC

FDA RSABE is ISC [🇷 for BE/BA]

posted by d_labes – Berlin, Germany, 2020-07-15 20:13 (1373 d 16:30 ago) – Posting: # 21703
Views: 16,732

Hi Helmut, Hi ElMaestro,

❝ ...

❝ Well, the EMA’s models are wacky because they assume equal intra-subject variances of T and R. An assumption which was shown to be false in many cases. Essentially most of the information obtainable in a replicate design is thrown away.

Full ACK!

❝ I don’t know why the FDA does not directly estimate \(\small{s_\textrm{wR}^2}\) from the mixed model but work with the intra-subject contrasts of R instead. ...

I was always wondering about the different methodologies in the code of the progesteron guidance:

ISC analysis for estimating CVwR and decision for using RSABE or ABE based on this estimate
Mixed model analysis of the 90% CI of T-R (ABE analysis) in case of swR < 0.029356 (CVwR < 30%)
ISC analysis for estimating the point estimate of T-R including 90% CI and its use in the RSABE criterion in case of swR >= 0.029356 (CVwR >= 30%)

Why not use the ISC estimate of T-R in the ABE decision in case of swR < 0.029356 (CVwR < 30%)?
Politics? Nostalgia (Since years recommended the Proc MIXED code)?

Or the other way round: Why not use the components of the RSABE criterion (pe and 90% CI, s2wR) from the mixed model approach?

I would opt for the full ISC approach because it may be unambiguously implemented in SAS, R, Phoenix and so on for every replicate design, full or partial :cool:

—
Regards,

Detlew

Complete thread:

Semireplicated + REML in R ElMaestro 2020-07-10 13:19 [🇷 for BE/BA]
- Semireplicated + REML in R Helmut 2020-07-10 19:03
  - Semireplicated + REML in R ElMaestro 2020-07-10 19:24
    - Avoid partial replicate designs, pleeeze! Helmut 2020-07-11 11:57
      - Avoid partial replicate designs, pleeeze! ElMaestro 2020-07-11 14:43
        
        Braveheart! Helmut 2020-07-11 15:38
        
        Who can help? ElMaestro 2020-07-12 12:28
        
        Who can help? ElMaestro 2020-07-12 13:26
        Update II ElMaestro 2020-07-12 21:36
        
        Update III ElMaestro 2020-07-12 21:46
        
        Final update today ElMaestro 2020-07-12 22:27
        
        Medium rare. Helmut 2020-07-13 13:52
        
        took just 52 hrs to do it :-) ElMaestro 2020-07-13 14:18
        
        Will take much more hours still… Helmut 2020-07-13 15:34
        
        Negative determinant ElMaestro 2020-07-14 03:22
        
        Are we loosers? Helmut 2020-07-14 13:58
        
        "we"? Loosers? ElMaestro 2020-07-14 15:07
        
        Misunderstanding? Helmut 2020-07-14 15:32
        
        Braveheart! ElMaestro 2020-07-13 10:13
        
        Braveheart! Helmut 2020-07-13 14:16
        Braveheart! PharmCat 2020-07-15 14:19
        
        Braveheart! ElMaestro 2020-08-02 17:39
- We were all blind (except Detlew) Helmut 2020-07-15 14:27
  - It is the opposite way around for me ElMaestro 2020-07-15 16:25
    - Desultory thoughts Helmut 2020-07-15 17:33
      - FDA RSABE is ISCd_labes 2020-07-15 18:13
        
        FDA RSABE is ISC Helmut 2020-07-16 11:11
      - Desultory thoughts ElMaestro 2020-07-15 23:06
        
        Desultory thoughts Helmut 2020-07-16 10:59
  - Phoenix - which template? mittyri 2020-07-19 00:42
    - FDA RSABE Project template_ v1.4.phxproj Helmut 2020-07-19 01:45
- "By popular demand": likelihood ElMaestro 2020-07-24 10:07
  - And by the way.... ElMaestro 2020-07-24 12:52
    - And by the way.... PharmCat 2020-08-03 14:24
      - Not understood ElMaestro 2020-08-03 22:55
        
        Not understood PharmCat 2020-08-05 01:41
        
        Not understood ElMaestro 2020-08-05 08:13
        
        Not understood PharmCat 2020-08-05 16:37
        
        Open issues ElMaestro 2020-08-06 21:11
        
        Open issues PharmCat 2020-08-07 00:02
        
        Open issues ElMaestro 2020-08-07 07:49
        
        Open issues PharmCat 2020-08-07 11:29
        
        Still can't make it work ElMaestro 2020-08-07 13:08
        
        Still can't make it work PharmCat 2020-08-07 15:42
        
        Still can't make it work ElMaestro 2020-08-07 16:44
        
        Still can't make it work PharmCat 2020-08-07 18:14
        
        Still can't make it work ElMaestro 2020-08-07 18:23
        
        And now it works ElMaestro 2020-08-07 21:31
        Still can't make it work PharmCat 2020-08-08 01:08
        
        Speed improvement ElMaestro 2020-08-08 12:25
        
        Speed improvement PharmCat 2020-08-08 17:27
        Speed improvement ElMaestro 2020-08-08 18:10
        
        Speed improvement PharmCat 2020-08-09 18:22
        Some tests... PharmCat 2020-08-10 11:48