Optimal designs for dose finding studies with an active control
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Date
2011-09-28
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Abstract
Dose finding studies often compare several doses of a new compound with a marketed
standard treatment as an active control. In the past, however, research has
focused mostly on experimental designs for placebo-controlled dose finding studies. To
the best of our knowledge, optimal designs for dose finding studies with an active control
have not been considered so far. As the statistical analysis for an active controlled
dose finding study can be formulated in terms of a mixture of two regression models,
the related design problem is different to what has been investigated before in the
literature. We present a rigorous approach to the problem of determining optimal designs
for estimating the smallest dose achieving the same treatment effect as the active
control. We determine explicitly the locally optimal designs for a broad class of models
employed in such studies. We also discuss robust design strategies and determine
related Bayesian and standardized minimax optimal designs. We illustrate the results
by investigating alternative designs for a clinical trial which has recently appeared in
a consulting project of one of the authors.
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Keywords
minimax design, active control, dose estimation, dose response, Bayesian optimal designs