Silva
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Portugal,
2014-02-26 13:27
(3683 d 12:04 ago)

Posting: # 12502
Views: 5,440
 

 Randomization procedure with gender strati­fication [Design Issues]

Dear all

Does it make any sense covering in the randomization procedure in SAS, gender stratification for BE studies? Despite FDA refers that BE study data is not expected to have sufficient power to draw conclusions for each subgroup and therefore statistical analysis of subgroups is not recommended, do you think in a near future this may overcome?

Best regards
Silva
Helmut
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Vienna, Austria,
2014-02-26 14:34
(3683 d 10:57 ago)

@ Silva
Posting: # 12505
Views: 4,689
 

 If possible, yes.

Hi Silva,

❝ Does it make any sense covering in the randomization procedure in SAS, gender stratification for BE studies?


If the sample size is sufficiently large, why not? I doesn’t hurt. If you don’t stratify – by stupid chance – you might end up with extremely imbalanced sequences within subgroups. That’s not desirable.

❝ Despite FDA refers that BE study data is not expected to have sufficient power to draw conclusions for each subgroup and therefore statistical analysis of subgroups is not recommended, do you think in a near future this may overcome?


I don’t think so. But you never know what may come into the mind of assessors. ;-)

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Silva
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Portugal,
2014-02-26 14:41
(3683 d 10:50 ago)

@ Helmut
Posting: # 12507
Views: 4,706
 

 If possible, yes.

Hi Helmut,

Regarding your comment:

❝ If the sample size is sufficiently large, why not? I doesn’t hurt. If you don’t stratify – by stupid chance – you might end up with extremely imbalanced sequences within subgroups. That’s not desirable.


What do you consider a sufficiently large sample size? ≥34? ≥46? ≥56?

Regards
Helmut
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Vienna, Austria,
2014-02-26 14:53
(3683 d 10:38 ago)

@ Silva
Posting: # 12509
Views: 4,682
 

 Trial and error

Hi Silva,

❝ What do you consider a sufficiently large sample size? ≥34? ≥46? ≥56?


“Sufficiently large” is the term commonly used by statisticians if they want to stay vague and don’t have the balls to come up with a particular number. :-D
Simply give it a try. I guess that for small sample sizes (e.g., 12) in the worst case you will have to start the randomization-algo more than once – with different seeds – in order to get everything balanced.

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Silva
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Portugal,
2014-02-26 15:05
(3683 d 10:25 ago)

@ Helmut
Posting: # 12510
Views: 4,711
 

 Trial and error

Hi Helmut,

Many thanks. It's a precisous help!

Best regards
ElMaestro
★★★

Denmark,
2014-02-26 15:45
(3683 d 09:45 ago)

@ Helmut
Posting: # 12512
Views: 4,712
 

 Trial and error

Hi Hötzi,

❝ Simply give it a try. I guess that for small sample sizes (e.g., 12) in the worst case you will have to start the randomization-algo more than once – with different seeds – in order to get everything balanced.


I think FDA would issue a 483 if anyone does that.

Pass or fail!
ElMaestro
Helmut
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Vienna, Austria,
2014-02-26 15:52
(3683 d 09:38 ago)

@ ElMaestro
Posting: # 12513
Views: 4,682
 

 SOPitis

Hi ElMaestro,

❝ I think FDA would issue a 483 if anyone does that.


Write a macro in SAS which loops until balance is obtained. Write an SOP. Get many signatures (aka dissipation of responsibilities).
Or would you prefer to push the button once and end up with all females in sequence RT and the males in TR? :pirate:

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ElMaestro
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Denmark,
2014-02-26 18:10
(3683 d 07:20 ago)

@ Helmut
Posting: # 12516
Views: 4,666
 

 SOPitis

Hi Hötzi,

❝ Write a macro in SAS which loops until balance is obtained. Write an SOP. Get many signatures (aka dissipation of responsibilities).

❝ Or would you prefer to push the button once and end up with all females in sequence RT and the males in TR? :pirate:


Yah, it is a borderline case.
I think I would word the protocol and study title carefully. The study is not really randomised if some randomisations are better than others. This is when I think stratification must be part of the wording.

For Xovers I wouldn't normally have a worry as long as we talk non-Brazilian and non-Japanese submissions. For parallel studies I might be inclined to stratify formally if two genders are necessary.

Pass or fail!
ElMaestro
mittyri
★★  

Russia,
2014-02-26 20:23
(3683 d 05:08 ago)

@ ElMaestro
Posting: # 12520
Views: 4,704
 

 SOPitis

Hi ElMaestro & all!

❝ I think I would word the protocol and study title carefully. The study is not really randomised if some randomisations are better than others. This is when I think stratification must be part of the wording.


Could you give an example of wording?
"Multicentre, single-dose, randomised, open label, two-sequence, two-period, crossover, bioavailability study in male and female patients under fed conditions with gender stratification" - something like that?

Would stratification be applicable in BEQ studies from assessors point of view? Any experience?

Kind regards,
Mittyri
ElMaestro
★★★

Denmark,
2014-02-26 23:31
(3683 d 02:00 ago)

@ mittyri
Posting: # 12522
Views: 4,694
 

 SOPitis

Hi Mittyri,

❝ Could you give an example of wording?

❝ "Multicentre, single-dose, randomised, open label, two-sequence, two-period, crossover, bioavailability study in male and female patients under fed conditions with gender stratification" - something like that?


Yes, or simply "Multicentre, single-dose, gender-stratified, randomised, open label, two-sequence, two-period, crossover, bioavailability study under fed conditions."

❝ Would stratification be applicable in BEQ studies from assessors point of view? Any experience?


I think so but I am hard pressed to think of a common situation where it would be really relevant.

Pass or fail!
ElMaestro
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