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

posted by Ben – 2018-06-12 21:14 (1936 d 19:12 ago) – Posting: # 18892
Views: 14,378

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 (n2) will be higher if we use a low n1.

Me too.

❝ If we base n1 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. :-D

Best regards,

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