Bioequivalence and Bioavailability Forum

msmnainar ★ India, 2021-06-22 16:24 (1417 d 16:41 ago) Posting: # 22426 Views: 3,611	Randomization [General Statistics] Post reply
	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
★★★

Vienna, Austria,
2021-06-22 17:05
(1417 d 15:59 ago)

@ msmnainar
Posting: # 22427
Views: 2,865

2:1 allocation

Post reply

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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Helmut Schütz

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msmnainar
★

India,
2021-06-23 18:49
(1416 d 14:15 ago)

@ Helmut
Posting: # 22428
Views: 2,826

2:1 allocation

Post reply

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

Randomization [General Sta­tis­tics]

2:1 allocation

2:1 allocation

Randomization [General Statistics]