Silva
☆    

Portugal,
2014-04-17 10:57
(3634 d 04:30 ago)

Posting: # 12846
Views: 2,541
 

 BE trial design as partial replicate and two stage [Regulatives / Guidelines]

Dear all

Is it advisable to use two stage design approach in partial replicate design?
If yes, which alpha level should be used for the second stage (combined stage I + stage II data)?

Best regards
Silva
ElMaestro
★★★

Denmark,
2014-04-17 11:17
(3634 d 04:10 ago)

@ Silva
Posting: # 12847
Views: 1,636
 

 BE trial design as partial replicate and two stage

Hi Silva,

❝ Is it advisable to use two stage design approach in partial replicate design?

❝ If yes, which alpha level should be used for the second stage (combined stage I + stage II data)?


There are no publications about two-stage studies and replicated designs of any type. Therefore I would only attempt to do it after a scientific advice. They may ask you to prove by your own simulations if/how the method performs in various scenarios.

Pass or fail!
ElMaestro
Silva
☆    

Portugal,
2014-04-17 11:36
(3634 d 03:51 ago)

@ ElMaestro
Posting: # 12848
Views: 1,690
 

 BE trial design as partial replicate and two stage

Hi Helmut
Once I met someone with the same doubts and he told me that he have asked for a CHMP SA on the subject. As I remember from the talk, his opinion was that the agency was also not able to deal with this complex statistical analysis and therefore the advice was to consider the second stage group as a group effect and therefore only 90% CI's were calculated and not the 94.12%!

But this is not mandatory, as no public information is available!

Rgs


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]
Helmut
★★★
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Homepage
Vienna, Austria,
2014-04-17 17:33
(3633 d 21:54 ago)

@ Silva
Posting: # 12850
Views: 3,237
 

 EMA = PSRPH?

Hi Silva,

❝ […] a CHMP SA on the subject. As I remember from the talk, his opinion was that the agency was also not able to deal with this complex statistical analysis…


EMEA. The European Medicines Evaluation Agency.
The drug regulatory agency of the European Union.
A statistician-free zone.
         Stephen Senn (2004)


❝ … and therefore the advice was…


So they felt not to be “able to deal with this complex statistical analysis” and nevertheless gave an advice? Weird.

When you know something, say what you know.
When you don’t know something, say that you don’t know.
That is knowledge.
          Confucius


❝ … to consider the second stage group as a group effect and therefore only 90% CI's were calculated and not the 94.12%!


That’s bizarre and a potential serious risk to public health, Imho. Btw, a 94.12% CI (αadj 0.0294) is not a solution for everything. Some people (including myself) think that already EMA’s standard ABEL inflates the patient’s risk (see this thread). Two stages‽ If somebody does know a pro­cedure, please enlighten me.

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