Achievwin
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US,
2024-05-03 15:28
(77 d 23:29 ago)

Posting: # 23975
Views: 2,661
 

 Large sample size in a BE study [Design Issues]

Dear All:

I came across a parallel BE study protocol that has around 900 subjects, has anyone seen BE study of this magnitude for a BE study in patients?

Kindly share your experience

Achievwin
Helmut
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Vienna, Austria,
2024-05-03 15:34
(77 d 23:24 ago)

@ Achievwin
Posting: # 23976
Views: 2,300
 

 My record: ≈400

Hi Achievwin,

❝ I came across a parallel BE study protocol that has around 900 subjects, has anyone seen BE study of this magnitude for a BE study in patients?


Define magnitude. :-D If you mean hundreds, yes. Multi-center in patients.
BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…

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Achievwin
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US,
2024-05-03 15:49
(77 d 23:09 ago)

@ Helmut
Posting: # 23978
Views: 2,263
 

 My record: ≈400

❝ Define magnitude. :-D If you mean hundreds, yes. Multi-center in patients.

❝ BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…


wow for a full replicate N=400 the sponsor has deep pockets…

Thanks for your response
Helmut
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2024-05-03 16:19
(77 d 22:39 ago)

@ Achievwin
Posting: # 23980
Views: 2,290
 

 My record: ≈400

Hi Achievwin,

❝ ❝ BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…

❝ wow for a full replicate N=400 the sponsor has deep pockets…

Nope. ≈400 (parallel), 180 4-period full replicate1 but there are even larger ones (252 subjects started, 238 completers).2 If your drug is a blockbuster1 and you have to change the formulation, you would do it.


  1. U.S. National Library of Medicine [2014-05-19] – Identifier NCT01290757
  2. Davit BM, Patel DT. Bioequivalence of Highly Variable Drugs. In: Yu LX, Li BV, editors. FDA Bioequivalence Standards. New York: aapspress/Springer; 2014. p. 151–2.

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nobody
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2024-05-03 20:44
(77 d 18:13 ago)

@ Helmut
Posting: # 23982
Views: 2,266
 

 My record: ≈400

❝ Define magnitude. :-D If you mean hundreds, yes. Multi-center in patients.

❝ BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…


Photos or it didn't happen. At least intraind CV :-P

Kindest regards, nobody
Helmut
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2024-05-04 00:25
(77 d 14:33 ago)

@ nobody
Posting: # 23983
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 n=180 4-period full replicate

Hi nobody,

❝ ❝ BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…


❝ Photos or it didn't happen. At least intraind CV :-P


Incidentally I know the backstory of #1 of the post above. It was very difficult to develop a new formulation. Pilot studies (plural!) with 80 subjects. No reference-scaling; however, CV was not the main problem. Sample size based on a best-guess T/R-ratio of 0.85. Do the maths.

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Achievwin
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US,
2024-05-06 17:56
(74 d 21:02 ago)

@ Helmut
Posting: # 23990
Views: 2,132
 

 n=180 4-period full replicate

❝ ❝ ❝ BTW, I have seen 4-period full replicate studies with 180 healthy volunteers…


High sample size is because it is an NTID and they have to document an additional parameter based on the variance ratios....

In my previous life we did two 3-period replicate design, satisfied guidance on the day we were supposed to submit the ANDA revised guidance was published brought the whole story to the start.
:confused::confused::confused:
mittyri
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Russia,
2024-05-07 09:35
(74 d 05:23 ago)

@ Achievwin
Posting: # 23991
Views: 2,064
 

 HVNTID!

Hi Achievwin,

❝ High sample size is because it is an NTID and they have to document an additional parameter based on the variance ratios....


This is HVNTID! :-D
A must read thread about Dabigatran, this study and Originator's hard life

Kind regards,
Mittyri
dshah
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India/United Kingdom,
2024-05-08 18:11
(72 d 20:47 ago)

@ Helmut
Posting: # 23992
Views: 1,990
 

 n=180 4-period full replicate

Hi Helmut!

According to me, there is clear requirement to improve T/R ratio from 0.85 to at least 0.9 which can reduce the sample size as well.
Regards,
Divyen
Helmut
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Vienna, Austria,
2024-05-08 18:18
(72 d 20:40 ago)

@ dshah
Posting: # 23993
Views: 1,988
 

 Lousy T/R-ratio

Hi Divyen,

❝ According to me, there is clear requirement to improve T/R ratio from 0.85 to at least 0.9 which can reduce the sample size as well.

I agree, of course, but see above. The company tried, but to no avail. I don’t remember how many times reformulation was done – always followed by a pilot study. It was not possible to do it better…

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Achievwin
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US,
2024-05-17 15:45
(63 d 23:13 ago)

@ dshah
Posting: # 24000
Views: 1,513
 

 n=180 4-period full replicate

❝ there is clear requirement to improve T/R ratio from 0.85 to at least 0.9 -


that is commonsense if you ask a BE guy..... then formulators show 100s for documents that the formulations compare "Spot on" then starts navigation through muddy waters.
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