Bioequivalence and Bioavailability Forum • Crossover designs with more than 2 treatments

Crossover designs with more than 2 treatments [Design Issues]

posted by d_labes – Berlin, Germany, 2012-11-27 10:51 (4161 d 09:31 ago) – Posting: # 9599
Views: 21,449
(edited by d_labes on 2012-11-27 15:39)

Dear Noha,

❝ Is it ok to use this study design?

Yes. Why not?
For issues of which sequences to use see this thread and try these searches: 1, 2.

Eventually you have to consider multiplicity issues. See the reference given in this post.

❝ How will this affect ANOVA analysis?

The ANOVA model is the same as for the classical 2x2 cross-over. But implicit the assumption of the equal intra-subject variability for all three study drugs/formulations has to be taken.

The mighty Oracle EMA has its own belief how to evaluate such studies. See the EMA guideline page 14 under Subject accountability.

❝ Is this design referred to as two-way or three-way?

In a sloppy language: Yes for the second choice.
Exactly: None of both. The terms 'two-way' or 'three-way' names ANOVA with two or three factors in the model, usually crossed.

It would be better to call these designs 3-treatment-3(or6)-sequence-3-period design or shortly 3x3x3 or 3x6x3.

After reading the posts of ElMaestro and Dan I must confess that I simply overlooked the sentence "from two different manufacturers".
If the study is really aimed for two sponsors: This raises doubts for using a 3x3x3 or 3x6x3 crossover.

—
Regards,

Detlew

Complete thread:

Two Tests with Same Reference Noha Abdeljawad 2012-11-27 08:18 [Design Issues]
- Crossover designs with more than 2 treatmentsd_labes 2012-11-27 09:51
  - Crossover designs with more than 2 treatments Noha Abdeljawad 2012-11-29 07:43
- Sounds wrong to me ElMaestro 2012-11-27 12:10
  - Sounds wrong to me Dr_Dan 2012-11-27 14:32
  - Sounds wrong to me Noha Abdeljawad 2012-11-29 07:52
- Two Tests with Same Reference jag009 2012-11-28 21:26
  - FDA & multiplicity Helmut 2012-11-30 14:04
    - FDA & multiplicity jag009 2012-11-30 15:16
      - FDA & multiplicity Helmut 2012-11-30 16:12
        
        FDA & multiplicity jag009 2012-11-30 22:47
        
        FDA & multiplicity Helmut 2012-12-01 02:00
        
        FDA & multiplicity jag009 2012-12-03 21:53
    - Multiplicity: Mixed feelings ElMaestro 2012-11-30 15:24
      - Multiplicity: Mixed feelings Helmut 2012-11-30 15:52
        
        Multiplicity: Mixed feelings martin 2012-12-03 09:24
      - Multiplicity: Mixed feelings kumarnaidu 2013-12-12 11:03
        
        More infos, please Helmut 2013-12-12 15:27
  - Two Tests with Same Reference Noha Abdeljawad 2012-12-03 08:29
    - Two Tests with Same Reference jag009 2012-12-03 15:35
      - X-way d_labes 2012-12-04 09:25
        
        design kvgreddy06 2013-12-19 15:32
        
        design kvgreddy06 2013-12-30 16:48
        
        design intuitivepharma 2013-12-31 06:44
        
        design kumarnaidu 2013-12-31 08:24
        
        Problematic design Helmut 2013-12-31 15:02
        
        Problematic design kvgreddy06 2014-01-03 14:46
        Problematic design kumarnaidu 2014-12-24 12:56
        
        Problematic design Helmut 2014-12-24 16:10
        
        Problematic design kumarnaidu 2014-12-26 05:38
        
        Two fully replicated designs? Helmut 2014-12-27 15:52