Universally optimal crossover designs for the estimation of mixed-carryover effects with an application to biosimilar development
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Date
2018
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Abstract
Biosimilars are medical products that are developed as copies of already
established, large molecule drugs (biologics). For gaining approval, sponsors have to
confirm that the proposed biosimilar has the same efficacy and safety as the originator
product. This comparability exercise includes also, in most cases, that large clinical
trials are conducted in patients. However, even with the evidence gained during the
clinical studies, there is still some uncertainty if patients who were already treated
with the originator can be switched to the biosimilar or if even multiple switches between
the biosimilar and the originator are acceptable. A simple way to address the
question of switchability is the estimation of so-called mixed and self-carryover effects,
which are carryover effects that not only depend on the treatment in the current
period, but also on the treatment in the previous period. In this paper, we determine
universally optimal designs for the estimation of mixed-carryover effects in a linear
model with treatment, period, subject and self-carryover as nuisance parameters.
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Keywords
biosimilars, switchability, crossover design, mixed-carryover effects, self carryover effects