Mithu
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India,
2022-07-25 06:39
(21 d 01:20 ago)

Posting: # 23165
Views: 338
 

 BCS Class II & IV molecule [Power / Sample Size]

Dear All,

Is it advisable to have little large sample size for molecules falls under BCS Class II and IV? especially when routine 2WC design is selected?

Regards,

Mithu


Edit: Category changed; see also this post #1[Helmut]
dshah
★    

India/United Kingdom,
2022-07-25 09:44
(20 d 22:14 ago)

@ Mithu
Posting: # 23166
Views: 295
 

 BCS Class II & IV molecule

Dear Mithu!
It's mainly based on your estimated T/R ratio, ISCV, desired Power.
Regards,
Divyen
Mithu
☆    

India,
2022-07-25 10:56
(20 d 21:02 ago)

@ dshah
Posting: # 23170
Views: 282
 

 BCS Class II & IV molecule

» Dear Mithu!
» It's mainly based on your estimated T/R ratio, ISCV, desired Power.
correct sir. but here the case is, we are dealing with tech. transfer products where we could not do much with the test formulation and some times, old RLD also not available in market.

regards,

Mithu
Helmut
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Vienna, Austria,
2022-07-25 09:56
(20 d 22:03 ago)

@ Mithu
Posting: # 23167
Views: 295
 

 in vivo ≠ in vitro

Hi Mithu,

» Is it advisable to have little large sample size …

Larger than what?

» … for molecules falls under BCS Class II and IV? especially when routine 2WC design is selected?

Only in a few cases of BCS class II drugs (under certain conditions) there is an in vivo in vitro correlation. For BCS class IV drugs never. You plan the study always based on the in vivo variability and T/R-ratio for a desired power. In other words, BCS does not play any role.

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Mithu
☆    

India,
2022-07-25 10:54
(20 d 21:05 ago)

@ Helmut
Posting: # 23169
Views: 280
 

 in vivo ≠ in vitro

» Larger than what?

Larger then needed from expected variability. if observed variability gives samples size around 48 than can we take more than that i.e. around 60.

» Only in a few cases of BCS class II drugs (under certain conditions) there is an in vivo in vitro correlation. For BCS class IV drugs never. You plan the study always based on the in vivo variability and T/R-ratio for a desired power. In other words, BCS does not play any role.

Here the case is, we are dealing with some technology transfer products in which we could not change our test formulation which was meet the BE marginally at the time of initially filing. now due to this bottle neck, our thinking is if we take little large sample size, than we can manage variability (my expectation may be not correct).

Hope I could place my point correctly.

Regards,

Mithu


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 #5[Helmut]
dshah
★    

India/United Kingdom,
2022-07-25 11:19
(20 d 20:39 ago)

@ Mithu
Posting: # 23171
Views: 275
 

 in vivo ≠ in vitro

Hi Mithu!

» Here the case is, we are dealing with some technology transfer products in which we could not change our test formulation which was meet the BE marginally at the time of initially filing. now due to this bottle neck, our thinking is if we take little large sample size, than we can manage variability (my expectation may be not correct).

As per regulatory acceptance- it is either acceptable or unacceptable. So is not best to describe it as marginally acceptable.

The in vitro assessment with recent batches of reference is important and also performing a comparative dissolution with older lot (if still available) can be useful.

Taking only larger size without consideration of in vitro assessment will not solve your problem.

Regards,
Divyen Shah
Mithu
☆    

India,
2022-07-25 13:26
(20 d 18:33 ago)

@ dshah
Posting: # 23175
Views: 255
 

 in vivo ≠ in vitro

» As per regulatory acceptance- it is either acceptable or unacceptable. So is not best to describe it as marginally acceptable.

Just to make it clear that I am trying to say that study is passing at 80.5% lower CI.

» The in vitro assessment with recent batches of reference is important and also performing a comparative dissolution with older lot (if still available) can be useful.
»
» Taking only larger size without consideration of in vitro assessment will not solve your problem.

Thank you.

Regards,
Helmut
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Vienna, Austria,
2022-07-25 13:02
(20 d 18:57 ago)

@ Mithu
Posting: # 23173
Views: 261
 

 Assumptions

Hi Mithu,

» » Larger than what?
» Larger then needed from expected variability. if observed variability gives samples size around 48 than can we take more than that i.e. around 60.

Apart from Divyen’s comments above, make yourself familiar with the basics of sample size estimation, especially the section dealing with assumptions.

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Mithu
☆    

India,
2022-07-25 13:24
(20 d 18:35 ago)

@ Helmut
Posting: # 23174
Views: 256
 

 Assumptions

» […] make yourself familiar with the basics of sample size estimation, especially the section dealing with assumptions.

Okay. I will do that. thank you for your reply.

regards,


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 #5[Helmut]
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