Some more "answers" [Two-Stage / GS Designs]

posted by d_labes  – Berlin, Germany, 2018-04-29 21:11 (834 d 14:10 ago) – Posting: # 18741
Views: 9,249

Dear Michael,

just my two cents.

» 1. I'm trying to compare the old function
» ...
» So the old function was nice since the user can choose the method or specify 3 alphas.
» In the new one I see the comment regarding alpha
» If one element is given, the overall one-sided significance level. If two elements are given, the adjusted one-sided alpha levels for stage 1 and stage 2, respectively.
» If missing, defaults to 0.05.
» What about alpha0 for method C? Is it deprecated?

Sorry for confusion, but you definitely have to study the references (start with 1)) to get a clue whats going on with this new function(s) implementing a new method for evaluating TSDs. New in the sense that it was not implemented in Power2Stage and was not applied in the evaluation of TSDs up to now.
It's by no means a method adding to or amending the Potvin methods.
It is a new method with a different philosophy behind.
And this method, combination of p-values of applying the TOST with the data of the two stages separately, is said to control the TIE rate at <=0.05, regardless of what design changes are done during interim, e.g. re-estimation of the sample size at interim analysis. And this is not proven by simulations, but in theory, by proof. A feature which is demanded by EMA statisticians. Do you remember the statement "Potvin's methods are not valid / acceptable in Europe"?
Exept Russia which is at least to some extent also in Europe IIRC...

» 2. Why did you decide to include CI futility rule by default?

See Helmut's answer. Maurer et al. have included a CI futility rule in their paper.
And it's our behavior to set defaults according to the (first) paper(s) describing TSD evaluation methods. Ok, that may be sub-optimal in comparing methods, since you always have to remember the defaults and differences within them for different functions.
But, ...
The re-calculation or verification of results comes first. And my lazyness calls for defaults resembling the details done in the paper(s) after wich a function in Power2Stage was implemented.

» 3. Regarding your flowchart:
» isn't it possible that we get some value lower than 4?

See Helmut's answer.
Since min.n2<4 doesn't make sense it is restricted to >=4. As described in the Maurer et al. paper.

» 4. Is it possible to update the docs attached to the library?

Not quite clear for me what we should update. Could you please elaborate?

» 5. I was confused with "2stage" 'aliased' with "tsd" and was looking for differences some time
» Are there any reasons to double that functions?

The real reason behind this change is lazyness of mine (sic!). It saves me 3(!) keystrokes :cool:. Believe it or not ...

Don't hesitate to ask more "naive" question. We all here, including not at least me, are naive with respect to this new method of evaluating TSDs.
If you feel more comfortable ask me or Helmut or Ben via the private way. I.e. write to the maintainer of Power2Stage ;-).

1) Maurer W, Jones B, Chen Y. Controlling the type 1 error rate in two-stage sequential designs when testing for average bioequivalence. Stat Med. 2018;37(10):1–21. doi:10.1002/sim.7614.

Drop me a Mehl if you need that sheet of paper.



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