2-stage design with interim sample size estimation [Two-Stage / GS Designs]

posted by d_labes  – Berlin, Germany, 2010-10-05 15:09 (3594 d 01:47 ago) – Posting: # 5997
Views: 11,602

Dear all,

I have been questioned about the following design:

The sponsor/experimenter has no sufficient information about CV and point estimate ('true' value) to be able to make an "educated" guess of the sample size for a BE study. Some distinct shift in the point estimator is expected.

To save resources (its a fixed combination drug with 3 constituents, analytical expensive) he is not willing to do a pilot study and based on this a pivotal with BE decision not using the data from the pilot.

Thus the design shall be a 2-stage design. A first group of subjects (conception is 8-12) shall be dosed, analyzed and statistical evaluated. Based on the data (CV and point estimate) a final sample size shall be derived which will be utilized for the second stage.

There is the idea of a formal extreme small alpha to spend after the first stage =0.001 (to conform EMA guideline). This will ensure with great probability that the second stage will be reached. Practical no stopping will occur by that.

The only stopping rule is a maximum sample size constraint Nmax the sponsor is willing to fund. If the estimated sample size after stage 1 is greater the second stage will not performed.

Any body out there who knows how to handle such a design?
Is there something to do to protect the overall alpha (lower nominal alpha at second stage)?
Is the sample size estimation done as usually?

Any input will be highly appreciated.



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