Bioequivalence and Bioavailability Forum

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

posted by Ben – 2018-06-12 21:14 (2312 d 00:24 ago) – Posting: # 18892
Views: 16,443

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.

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
  • 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* examplesBen 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
                        • Binding / Nonbinding futility rule - alpha control Ben 2019-03-30 09:52