## Now what? w & w* examples [Two-Stage / GS Designs]

Hi Helmut,

» Not necessarily good but a “guesstimate”.

Got it. Well... whatever a guesstimate is

» » … but in case we observe some unforeseen value we have the possibility to add some extra subjects.

» » However, in such a case we could just go with a fixed design and adapt the Power.

»

» I’m not sure what you mean here. In a fixed sample design I would rather work with the upper CL of the CV or – if not available – assume a reasonably higher CV than my original guess rather than fiddling around with power.

I try to explain. In case the argument is that a TSD approach should be performed not because of an uncertain CV per se (e.g. quite a big range observed so far) but because it is desired to safeguard against an unfavorable outcome of the CV (i.e. an extreme realization / random deviate of the CV), then: stop right there. To protect against such an outcome is exactly the definition of Power (type II error) and I would question whether a TSD is really the right tool - maybe a fixed design already suffices (with a proper Power).

» » In a TSD setting we typically have no good understanding about the CV... Do I miss something here?

» (1) Yep and (2) no.

» » Based on what assumptions would we select n1 (= fixed design sample size)? We typically have some range of possible values and we don't know where we will be.

» I was just quoting a regulatory statistician (don’t want to out him). Others didn’t contradict him. So likely he wasn’t alone with his point of view.

» Very interesting. I expected that the sample size penalty (n

Me too.

» If we base n

» The pessimistic approach would be crazy.

I agree to all of it.

Best regards,

Ben.

» Not necessarily good but a “guesstimate”.

Got it. Well... whatever a guesstimate is

» » … but in case we observe some unforeseen value we have the possibility to add some extra subjects.

» » However, in such a case we could just go with a fixed design and adapt the Power.

»

» I’m not sure what you mean here. In a fixed sample design I would rather work with the upper CL of the CV or – if not available – assume a reasonably higher CV than my original guess rather than fiddling around with power.

I try to explain. In case the argument is that a TSD approach should be performed not because of an uncertain CV per se (e.g. quite a big range observed so far) but because it is desired to safeguard against an unfavorable outcome of the CV (i.e. an extreme realization / random deviate of the CV), then: stop right there. To protect against such an outcome is exactly the definition of Power (type II error) and I would question whether a TSD is really the right tool - maybe a fixed design already suffices (with a proper Power).

» » In a TSD setting we typically have no good understanding about the CV... Do I miss something here?

» (1) Yep and (2) no.

» » Based on what assumptions would we select n1 (= fixed design sample size)? We typically have some range of possible values and we don't know where we will be.

» I was just quoting a regulatory statistician (don’t want to out him). Others didn’t contradict him. So likely he wasn’t alone with his point of view.

» Very interesting. I expected that the sample size penalty (n

_{2}) will be higher if we use a low n_{1}.Me too.

» If we base n

_{1}on the lower end*and*the CV is close to the guesstimate that’s the winner. One the other hand there is a ~56% chance of proceeding to the second stage which is not desirable – and contradicts the concept of a “safety net”. A compromise would be 75% of the fixed sample design.» The pessimistic approach would be crazy.

I agree to all of it.

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 rule - Ben, 2018-06-15 17:58
- Binding / Nonbinding futility rule - alpha control - d_labes, 2018-06-16 19:42

- Nonbinding futility rule - Ben, 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