msmnainar
★    

India,
2021-06-22 14:24
(34 d 10:05 ago)

Posting: # 22426
Views: 503
 

 Randomization [General Sta­tis­tics]

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 15:05
(34 d 09:23 ago)

@ msmnainar
Posting: # 22427
Views: 420
 

 2:1 allocation

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 16:49
(33 d 07:39 ago)

@ Helmut
Posting: # 22428
Views: 277
 

 2:1 allocation

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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