Yura
★    

Belarus,
2021-05-27 12:25
(16 d 01:55 ago)

Posting: # 22372
Views: 371
 

 Dose normalization [Study Per­for­mance]

Hello everybody!
There is such a question: if the drug dose is calculated on the basis of the patient's body surface area, how can one take into account the fact that some patients will not receive the actual dose, but will receive a smaller dose when assessing BD / BE (2x2x2 design)? Is it necessary in this case to use corrections when estimating the PK parameters (how to carry out normalization)? For example, the patient will receive a dose of 30mg instead of the current 50mg.:
BSA(m2) Actual Dose  Dose for study
…           30            30
…           40            30
…           50            30
…           60            60
…           70            60
…           80            60
…           90            90

Do you need to check for BSA homogeneity of two groups of sequences?
Thank you
Relaxation
★    

Germany,
2021-05-27 15:29
(15 d 22:51 ago)

@ Yura
Posting: # 22373
Views: 332
 

 Dose normalization

» will not receive the actual dose, but will receive a smaller dose when assessing BD / BE (2x2x2) design)?

Hello yura.

I am sorry, but I am a little bit in a hurry and just wanted to start the answers here with one single comment.
As you are in a cross-over situation and assuming that the dose (BSA) of a subject will not change between periods, there is no need for a dose-adjustment with regard to the treatment comparison. Or the other way around: as you compare intraindividually the dose-adjustment would cancel out anyway.

Best regards!
Yura
★    

Belarus,
2021-05-28 10:22
(15 d 03:58 ago)

@ Relaxation
Posting: # 22374
Views: 270
 

 Dose normalization

Hello, Relaxation
OK. Patients will take different doses depending on the calculated BSA (for example, 30 - 60 - 90 - do not consider "actual" doses for now). And when assessing, there is no need to do normalization, for example, for a single dose of 30mg?

Best regards!
mittyri
★★  

Russia,
2021-05-31 12:42
(12 d 01:38 ago)

(edited by mittyri on 2021-05-31 18:21)
@ Yura
Posting: # 22382
Views: 220
 

 Dose normalization

Dear Yura,

» Patients will take different doses depending on the calculated BSA (for example, 30 - 60 - 90 - do not consider "actual" doses for now). And when assessing, there is no need to do normalization, for example, for a single dose of 30mg?

I cannot remember any examples where dose normalization was recommended by authorities. Indeed, there are contrary examples here and here.
mainly due to the fact that the volunteer's data controls itself in crossover studies

But you should be aware of the case with different strengths aka different products (i.e. 50+10 mg, 40 mg) - see here
AFAIK in such case there's no good solution.

Kind regards,
Mittyri
Yura
★    

Belarus,
2021-06-01 09:23
(11 d 04:57 ago)

@ mittyri
Posting: # 22383
Views: 204
 

 Dose normalization

Dear mittyri,
Thank you for the prompt reply and links
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