Dr Ripal
☆    

India,
2016-06-09 16:08
(2848 d 22:14 ago)

Posting: # 16417
Views: 7,009
 

 how to evaluate site/center effect in multicentric bioequivalence study? [General Sta­tis­tics]

Hi,

We have been asked by USFDA to include site/centre effect in one of our multicenteric oncology bioequivalence study. Kindly suggest which statistical tests should be used for the same.


Edit: Category changed; see also this post #1. [Helmut]
BE-proff
●    

2016-06-09 17:03
(2848 d 21:18 ago)

@ Dr Ripal
Posting: # 16418
Views: 6,092
 

 how to evaluate site/center effect in multicentric bioequivalence study?

Hi Dr.Ripal,

I presume these guys are talking about ANOVA.

I also think that you can try to clarify it with request on FDA site - usually such requests are answered in several days.
mittyri
★★  

Russia,
2016-06-09 17:21
(2848 d 21:01 ago)

@ Dr Ripal
Posting: # 16419
Views: 6,293
 

 See some previous topics

Hi Dr Ripal,

please search the forum
For example here and here you can find some useful information.

Kind regards,
Mittyri
ElMaestro
★★★

Denmark,
2016-06-09 21:39
(2848 d 16:43 ago)

@ Dr Ripal
Posting: # 16421
Views: 6,055
 

 Site and Treatment as fixed.

Hi Dr Ripal,

❝ We have been asked by USFDA to include site/centre effect in one of our multicenteric oncology bioequivalence study. Kindly suggest which statistical tests should be used for the same.


BE in oncology often means a parallel design, so I think you will need a simple two-factor model with treatment and site as fixed effects in a PROC GLM or equivalent.

Pass or fail!
ElMaestro
Dr Ripal
☆    

India,
2016-06-10 07:57
(2848 d 06:25 ago)

@ ElMaestro
Posting: # 16424
Views: 6,057
 

 Site and Treatment as fixed.

❝ Hi all,


Thanks a lot for your suggestions.

To be precise it is single dose two way cross over study of one of the taxanes and I am looking for the literature which supports evaluation of site effect and/or disease effect in bioequivalence studies.

I have not come across literature of any patient based bioequivalence study which evaluates site effect as variable in statistical analysis.
ElMaestro
★★★

Denmark,
2016-06-10 09:17
(2848 d 05:05 ago)

@ Dr Ripal
Posting: # 16426
Views: 5,984
 

 Site and Treatment as fixed.

Hi Dr Ripal,

❝ To be precise it is single dose two way cross over study of one of the taxanes and I am looking for the literature which supports evaluation of site effect and/or disease effect in bioequivalence studies.


Well, then it is a crossover and you need at least Site, Treatment, Sequence, Period, Subject in the model. Ideally Site has a high p-value.

❝ I have not come across literature of any patient based bioequivalence study which evaluates site effect as variable in statistical analysis.


Try harder. Google is your friend.

Pass or fail!
ElMaestro
DavidManteigas
★    

Portugal,
2016-06-15 20:30
(2842 d 17:52 ago)

@ Dr Ripal
Posting: # 16430
Views: 5,907
 

 how to evaluate site/center effect in multicentric bioequivalence study?

Hi,

Quoting E9:

"The statistical model to be adopted for the estimation and testing of treatment effects should be described in the protocol. The main treatment effect may be investigated first using a model which allows for centre differences, but does not include a term for treatment-by-centre interaction."

So imo the first step would be to include the centre effect in your model and check the significance. If the centre effect is significant, and given the nature of your endpoints, that would be a big trouble for you to explain. Being your study cross-over, maybe you should examine interactions between centre and sequence/group effect (question: was your randomization stratified by centre?). Analysis of multicentre data is dependent on the study features. For instance, if you have 50 centres with and average of 6~7 patients by centre maybe it is reasonable to include centre effects as random. However, if you have 2/3 centres with 30~40 patients per centre I would assess centre effects as fixed terms in the model and pray for non-significance :-D

It's hard to give an opinion without having a background on your study. However, I believe ICH E9 is quite clear in what you should do regarding your statistical analysis.
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