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

Dear Detlew,

» My first thought was: Set

»

»

» Your suggestion

»

» gives also n2=16. Astonishing or correct?

This is correct. Please note that if fCpower = 1, then (as intended) the futility criterion regarding power of stage 1 never applies. If you then encounter a scenario where

» Avoiding the conditional sample size re-estimation, i.e. using the conventional sample size re-estimation via

»

» gives n2=4. Ooops? Wow!

I have to think about that

» 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?

For example?

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

Non-binding: Type 1 error is protected, even if the futility criterion is ignored.

Binding: Type 1 error is protected only if the futility criterion will be adhered to. ('Binding' is not common practice, authorities don't want this).

Best regards,

Ben.

» 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)`

.»

» Your suggestion

»

`interim.tsd.in(GMR1=0.89, CV1=0.2575165, n1=38, ssr.conditional = "error")`

» gives also n2=16. Astonishing or correct?

This is correct. Please note that if fCpower = 1, then (as intended) the futility criterion regarding power of stage 1 never applies. If you then encounter a scenario where

*power of stage 1*is greater than`targetpower`

(this must not happen, but it *can*happen), then the conditional estimated target power will be negative. Thus, we would have a problem with this being the target power for sample size calculation. To avoid this from happening the function automatically sets the target power for recalculation to`targetpower`

(which is equivalent to ssr.conditional = "error"). See 'Details' in the man page.» 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!

I have to think about that

» 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?

For example?

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

Non-binding: Type 1 error is protected, even if the futility criterion is ignored.

Binding: Type 1 error is protected only if the futility criterion will be adhered to. ('Binding' is not common practice, authorities don't want this).

Best regards,

Ben.

### Complete thread:

- Finally: Exact TSD methods for 2×2 crossover designs Helmut 2018-04-21 17:17 [Two-Stage / GS Designs]
- Exact TSD methods: Example Helmut 2018-04-21 20:33
- Finally: Exact TSD methods for 2×2 crossover designs ElMaestro 2018-04-21 20:49
- Flow chart (without details) Helmut 2018-04-21 21:41
- naive questions regarding new functions in Power2Stage mittyri 2018-04-28 15:54
- Some answers Helmut 2018-04-28 17:29
- Some more "answers" d_labes 2018-04-29 21:11
- clarification regarding user Power2Stage guides mittyri 2018-04-30 13:41

- naive questions regarding new functions in Power2Stage mittyri 2018-04-28 15:54

- Flow chart (without details) Helmut 2018-04-21 21:41
- Technicality: Weigths for the inverse normal approach d_labes 2018-04-25 14:19
- Selection of w and w* Helmut 2018-04-26 09:51
- Selection of w and w* d_labes 2018-04-26 20:02
- Now what? w & w* examples d_labes 2018-05-09 13:53
- Now what? w & w* examples Ben 2018-06-10 20:12
- Now what? w & w* examples Helmut 2018-06-11 13:57
- Now what? w & w* examples Ben 2018-06-12 19:14

- a bug in interim.tsd.in()? mittyri 2018-06-11 23:27
- a bug in interim.tsd.in()? Ben 2018-06-12 19:32
- Nonbinding futility rule d_labes 2018-06-13 16:59
- Bad weather? Helmut 2018-06-13 19:23
- NLYW? d_labes 2018-06-14 10:18

- Nonbinding futility rule Ben 2018-06-13 20:26
- Nonbinding futility rule d_labes 2018-06-14 10:47
- Nonbinding futility ruleBen 2018-06-15 17:58
- Binding / Nonbinding futility rule - alpha control d_labes 2018-06-16 19:42
- Binding / Nonbinding futility rule - alpha control Ben 2019-03-30 09:52

- Binding / Nonbinding futility rule - alpha control d_labes 2018-06-16 19:42

- Nonbinding futility ruleBen 2018-06-15 17:58

- Nonbinding futility rule d_labes 2018-06-14 10:47

- Bad weather? Helmut 2018-06-13 19:23

- Nonbinding futility rule d_labes 2018-06-13 16:59

- a bug in interim.tsd.in()? Ben 2018-06-12 19:32

- Now what? w & w* examples Helmut 2018-06-11 13:57

- Now what? w & w* examples Ben 2018-06-10 20:12

- Selection of w and w* Helmut 2018-04-26 09:51