Bioequivalence and Bioavailability Forum • Replicated designs are relevant, too

Replicated designs are relevant, too [Software]

posted by ElMaestro – Denmark, 2014-10-07 14:36 (3865 d 05:15 ago) – Posting: # 13663
Views: 39,171

Hello yjlee,

❝ Why jump into '2-group parallel'? What about replicate?

2-group parallel are probably still the second-most common BE design, I think, and that's to me quite a good argument for prioritising it.

As you say, replicate designs are also relevant, but it would open up a can of worms:

EU all fixed effects (=normal linear model) versus US subject as random (=mixed model) and the EU vs US way of scaling.
Various modes of imbalance (missing period data or different numbers in TRTR and RTRT etc)
The use of denominator degrees of freedom as per Satterthwaite or something else; software limitations on the same matter.

Finally, I think noone that I know of doing BE is 100% well versed with the inner workings of mixed models or the syntactical wonders and settings of R, SAS, Nonlin, SPSS or whatever which to some extent would need deep understanding if we go the US route. With mixed models there will be quite a few potential choices to make and this is when the understanding matters a lot. For starters: Do we use REML and not ML because we have a read some webpages or books suggesting REML and not ML, or do we use REML because we have a deep understanding of the merits of REML and the lack of same for ML in the context of BE? Syntax for fits are complex regardless of language/package and how exp units are coded, e.g. "fm3 <- lmer(strength ~ (1|batch) + (1|batch:cask), Pastes)" and who really knows what all that "~" and "|" does for your ZGZ^t+R? If you use an option to do Kenward-Rogers are you then not compliant? And then there are the optimiser settings. And so forth.
Tricky, tricky, tricky.

—
Pass or fail!
ElMaestro

Complete thread:

reference dataset elba.romero 2013-07-02 05:08 [Software]
- Public datasets Helmut 2013-07-02 15:44
  - Public datasets yjlee168 2013-07-03 03:10
    - Public datasets elba.romero 2013-07-03 05:19
      - Public datasets yjlee168 2013-07-03 13:11
        
        Challenging data sets Helmut 2013-07-03 16:32
        
        Fantastic idea? ⇒ Challenging data sets yjlee168 2013-07-04 08:06
        
        Fantastic idea! Helmut 2013-07-04 13:18
    - NIST; cross-validation Helmut 2013-07-03 14:28
      - NIST; cross-validation yjlee168 2013-07-03 23:47
        
        NIST; cross-validation Helmut 2013-07-04 00:45
  - Public datasets elba.romero 2013-07-03 05:10
- Eight Reference Datasets (2×2×2 ☑) Helmut 2014-10-06 02:24
  - What??? ElMaestro 2014-10-06 13:20
    - What??? Helmut 2014-10-06 17:08
      - What??? ElMaestro 2014-10-06 17:31
        
        What the heck‽ Helmut 2014-10-06 19:05
  - link of electronic supplement material? yjlee168 2014-10-07 09:53
    - link of electronic supplement material? nobody 2014-10-07 10:59
      - Thanks! yjlee168 2014-10-07 11:35
        
        Thanks! nobody 2014-10-07 11:44
        
        Direct links & hint Helmut 2014-10-07 13:54
    - Replicated designs are relevant, tooElMaestro 2014-10-07 12:36
      - Replicated designs are relevant, too yjlee168 2014-10-07 13:00
        
        RSABE: SAS and PHX/WNL only? Helmut 2014-10-07 14:47
        
        for the future? yjlee168 2014-10-08 10:05
        
        Star Trek: The Next Generation Helmut 2014-10-09 00:26
        
        Star Trek: The Next Generation d_labes 2014-10-09 08:09
        Star Trek: The Next Generation nobody 2014-10-09 08:23
        Star Trek: The Next Generation yjlee168 2014-10-09 11:06
        
        Some comments ElMaestro 2014-10-09 11:52
        
        Some comments yjlee168 2014-10-09 12:18
        
        Proc MIXED - start value d_labes 2014-10-10 08:35
        
        Proc MIXED - start value ElMaestro 2014-10-10 11:44
        Proc MIXED - start value yjlee168 2014-10-11 21:09
        
        Proc MIXED - start value ElMaestro 2014-10-11 21:18
        
        Optimizer settings Helmut 2014-10-09 14:08
        
        Optimizer settings nobody 2014-10-09 15:32
        Optimizer settings yjlee168 2014-10-09 18:14
        
        FDA’s model… Helmut 2014-10-09 18:34
  - Just received a letter… Helmut 2014-11-03 14:54
  - 11 Reference Datasets (2-group parallel ☑) Helmut 2014-12-09 15:51