Loky do
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Egypt,
2020-05-22 18:16

Posting: # 21457
Views: 441
 

 Inclusion criteria in BE studies [Design Issues]

Dears
In BE studies, in case the participants are both males and females, should the ratio between them be 1:1 or any ratio is accepted, also for randomization procedure is there any special requirements in case both included?
Thanks


Edit: Category changed; see also this post #1[Helmut]
Helmut
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Vienna, Austria,
2020-05-23 17:12

@ Loky do
Posting: # 21458
Views: 381
 

 BE: ♀♂

Salam Loky do,

» […] participants are both males and females, should the ratio between them be 1:1 …

The FDA requires „subjects from the general population”; hence ~1:1. Though I have seen studies in males only as well. Possibly the ANVISA requires that as well.
AFAIK, in other jurisdictions there are no rules.

» … or any ratio is accepted, …

See above. I once saw a study were the protocol stated “females and males” and the the CRO recruited one female and 15 males. The study was accepted by European agencies but it looked stupid.

» … also for randomization procedure is there any special requirements in case both included?

See this thread and R-code for stratification there. IMHO, in crossover designs it does not make sense. Do we have “sex” as an effect in the model? No. Do we want to demonstrate BE separate for females and males? Generally not. If yes, we would have to double the sample size.
Parallel designs are another story, of course. Females/males should be evenly assigned to treatment groups.

Cheers,
Helmut Schütz
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jag009
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NJ,
2020-05-25 07:43

@ Loky do
Posting: # 21460
Views: 349
 

 Inclusion criteria in BE studies

Hi,

» In BE studies, in case the participants are both males and females, should the ratio between them be 1:1 or any ratio is accepted, also for randomization procedure is there any special requirements in case both included?

You should aim for 1:1 in the protocol but say at least 60:40 split (you can try 70:30 if you are desperate). I do that on my protocols for many yrs and no problem w FDA.

You should randomize w gender as well. I had one CRO who put the first 10 as males and then last 10 as females, lol. No I did not find that funny when I spoke w them.

J
Helmut
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Vienna, Austria,
2020-05-25 12:48

@ jag009
Posting: # 21461
Views: 343
 

 Stratify for sex?

Hi John,

» You should randomize w gender as well.

If it’s a cross-over, why? Sex is not part of the model.

» I had one CRO who put the first 10 as males and then last 10 as females, lol.

Reduced chance to “grab her by the p••••y” whilst lining up for phlebotomy.

» No I did not find that funny when I spoke w them.

I would.

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
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jag009
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NJ,
2020-05-25 21:10

@ Helmut
Posting: # 21465
Views: 302
 

 Stratify for sex?

Hi Helmut,

I was referring to generating the randomization list (you know, unlike the CRO who put first 10 males and next 10 females..)

» Reduced chance to “grab her by the p••••y” whilst lining up for phlebotomy.
» » No I did not find that funny when I spoke w them.
» I would.

Well if I had good impression of their overall capability, yes... But on not that day...

J


Edit: two successive posts merged [Ohlbe]
ElMaestro
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Belgium?,
2020-05-25 14:39

@ Loky do
Posting: # 21463
Views: 327
 

 Inclusion criteria in BE studies

Yah,

I agree with everything.
Just wish to mention that Gender is a between-subject factor (at least for most practical purposes ex-Thailand), so there is no particular gain in including Gender as a factor when you have Subject in the model unless there is a specific regulatory requirement.

While PK may be different between Genders, like it would be between old and young subjects, or smokers and non-smokers, African-Americans versus Eskimos etc. But in BE we are interested in the ratio of T/R and this ratio has never in any particularly good study proven to vary between sub-populations. Hence the relaxed attitude towards e.g. studies done in e.g. India for approval in US and so forth.
[Crystal ball] When the day comes, when someone is able to prove a case of real and true population difference in BE conclusion between populations, then BE as we know it today might be history and the innovator industry will jump on it like you would not believe possible with lawsuits left and right to protect their brands.[/Crystal ball]

I could be wrong, but...

Best regards,
ElMaestro

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