## Nonbinding futility rule [Two-Stage / GS Designs]

Dear Ben,

❝ The reference at page 19 actually refers to the CI futility criterion,

I know.

❝ ... in my opinion the only possibility is: if you want to be able to handle it in a nonbinding manner, then you have to go with conditional error rates only (i.e. you cannot use the estimated conditional target power as target power for calculation of n2). So, we would need to select ssr.conditional = "error".

My first thought was: Set fCpower = 1, that results in do not use the power futility criterion. This gives n2=16 for mittyri's example
interim.tsd.in(GMR1=0.89, CV1=0.2575165, n1=38, fCpower=1).

interim.tsd.in(GMR1=0.89, CV1=0.2575165, n1=38, ssr.conditional = "error")
gives also n2=16. Astonishing or correct?

Avoiding the conditional sample size re-estimation, i.e. using the conventional sample size re-estimation via
interim.tsd.in(GMR1=0.89, CV1=0.2575165, n1=38, ssr.conditional = "no")
gives n2=4. Ooops? Wow!

Helmuts caveat of how to decide in case of "nonbinding futility" needs to be considered, scientifically, not via NLYW .
IIRC the term "nonbinding" in the context of sequential designs is used for flexibility in stopping or continuing due to external reasons. Do we have such here?

Binding, nonbinding - does it have an impact on the alpha control? I think not, but are not totally sure.

Regards,

Detlew

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