Heteroscedasticity: TRT|RTR rulez! [RSABE / ABEL]

posted by d_labes  – Berlin, Germany, 2013-08-29 18:45 (4276 d 06:15 ago) – Posting: # 11387
Views: 10,308

(edited on 2013-08-30 09:23)

Dear Helmut! Dear All!

❝ ❝ Meanwhile I have some sims underway which (hopefully) will underpin my criticism of the TRT/RTR design.


❝ Kudos for your pioneering work on exploring heteroscedasticity. :-D


Thanks for the praise in advance. Let's see if I'm worth the "Vorschuss-Lorbeeren".

Going the long walk and simulating ABE type I error for the 3-period design with the sequences TRT and RTR via subject data sims (1 value after ~24 h!) I was more and more frustrated: No alpha-inflation, no too conservative alphas far and wide! Although the Oracle Chow&Liu had forecasted their certain occurrence!

But finally arriving in the green realms of FDA/ISC I got the following, resorting to heavy imbalance (forgot my Schützomycin dose :-D):

CVwT  CVwR   n1   n2   EMA     FDA
                       ANOVA   ISC
---------------------------------------
0.5   0.2   18   18   0.0509   0.0496*   
            21   15   0.0509   0.0559*
            15   21   0.0507   0.0430*
            24   24   0.0505   
---------------------------------------
0.5   0.3   18   18   0.0503   0.0502
            19   17            0.0516
            21   15   0.0502   0.0541
            15   21   0.0503   0.0459
---------------------------------------
0.2   0.5   18   18   0.0509   
            21   15   0.0511   
            15   21   0.0506      
            24   24   0.0505   
---------------------------------------
0.3   0.5   18   18   0.0505   0.0504
            19   17            0.0490
            21   15   0.0505   0.0469
            15   21   0.0503   0.0542
---------------------------------------
n1 = n(TRT), n2 = n(RTR)
1E6 sims, *1E5 sims only


There is no hint of an alpha-inflation or too conservative alpha values if one uses the EMA recommended evaluation (same ANOVA as for the classical 2x2x2 crossover), regardless of grade of heteroscedasticity and unbalancedness analyzed!

The evaluation via intra-subject contrasts also do not show noticeable deviations from the nominal level 0.05 as long as the design is balanced or only slightly unbalanced.
Alpha-inflation or too conservative type I error values are only observed if the sequence groups are strongly unbalanced.

Thus this design is much more ‘friendly’ in respect to heteroscedasticity than the 2x3x3 design in the EMA evaluation. See this post of mine.

Some simulations of power of scaled ABE show that even for heavy unbalanced designs the influence of this observed behaviour is only small.

Conclusion 1: TRT|RTR rulez! :-D
Conclusion 2: Expect an update of PowerTOST in the near future.

Regards,

Detlew

Complete thread:

UA Flag
Activity
 Admin contact
23,424 posts in 4,927 threads, 1,670 registered users;
138 visitors (0 registered, 138 guests [including 8 identified bots]).
Forum time: 01:00 CEST (Europe/Vienna)

Only dead fish go with the current.    Scuba divers' proverb

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5