msmnainar
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India,
2021-06-22 16:24
(1807 d 18:52 ago)

Posting: # 22426
Views: 5,470
 

 Randomization [General Sta­tis­tics]

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Hello all,

Need your expert opinion on the following,

Will there be any issue in adopting 2:1 (Test:Reference) randomization method in biosimilarity (BE) studies?

Note: The 2:1 randomization is mainly due to transition arm.
—
Sundar. M
 
Helmut
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Vienna, Austria,
2021-06-22 17:05
(1807 d 18:10 ago)

@ msmnainar
Posting: # 22427
Views: 4,391
 

 2:1 allocation

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Hi Sundar,

welcome back to the forum!

❝ Will there be any issue in adopting 2:1 (Test:Reference) randomization method in biosimilarity (BE) studies?


You will loose some power compared to equally sized treatment arms. For an [image]-script see there. It gives for an assumed CV 40% and T/R-ratio 0.95 targeted at 80% power:

n = 130 (1:1 allocation)
  nT = nR = 65
  power = 0.8035
n = 132 (naïve 2:1 allocation)
  nT = 88, nR = 44
  power = 0.7618
n = 147 (2:1 allocation)
  nT = 98, nR = 49
  power = 0.8060

If we desire a 2:1 allocation and want to preserve power, we need 13% more subjects than for the 1:1 allocation.

❝ Note: The 2:1 randomization is mainly due to transition arm.


What do you mean by that?
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msmnainar
★    

India,
2021-06-23 18:49
(1806 d 16:26 ago)

@ Helmut
Posting: # 22428
Views: 4,319
 

 2:1 allocation

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Hi Helmut,

Thanks for your detailed explanation.

❝ ❝ Note: The 2:1 randomization is mainly due to transition arm.

❝

❝ What do you mean by that?


Transition arm is in general re-randomization at certain week after efficacy evaluation (FDA requirement).

Basically, 1:1 randomization allocation would lead to a larger sample size for subjects transitioning from Reference to Test, which would allow for detecting differences in immunogenicity and safety.
—
Sundar. M
 
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