title: Are flexible designs sound?
abstract: Flexible designs allow large modifications of a design during an experiment. In particular, the sample size can be modified in response to interim data or external information. A standard flexible methodology combines such design modifications with a weighted test, which guarantees the type I error level. However, this inference violates basic inference principles. In an example with independent N(mu, 1) observations, the test rejects the null hypothesis of mu < or = 0 while the average of the observations is negative. We conclude that flexible design in its most general form with the corresponding weighted test is not valid. Several possible modifications of the flexible design methodology are discussed with a focus on alternative hypothesis tests.
authors.affiliation: AstraZeneca R & D, SE-431 83 Mölndal, Sweden. carl-fredrik.burman@astrazeneca.com
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Burman
authors.forename: Christian
authors.initials: C
authors.lastname: Sonesson
mesh_terms: D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016001:Confidence Intervals; D006801:Humans; D015233:Models, Statistical; D012107:Research Design; D018401:Sample Size