Abstract:
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Crossover design has been widely applied in late-phase clinical studies, as well as in PK/PD studies, bioequivalence studies, and medical device studies; however, its interpretability and applicability continue to be debated. In this paper, we provide discussions around a crossover design's scientific benefit, applicability, and how it can be implemented in late-phase diabetes studies by properly handling key issues: carryover effect, washout period, and baseline selection. Specifically, detailed considerations are provided about the validity and situations of having appropriate length of study duration to deal with carryover effects, so that a wash-out period may not be needed. A simulation study and data mining results on twelve crossover late-phase insulin clinical trials are also presented to examine the discussion points and proposals.
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