Abstract
The success or failure of a clinical trial, of any phase, depends critically on the
choice of an appropriate primary end-point. In the setting of phases II and III cancer
clinical trials, imaging end-points have historically, and continue presently to play
a major role in determining therapeutic efficacy. The primary goal of this paper is
to discuss the validation of imaging-based markers as end-points for phase II clinical
trials of cancer therapy. Specifically, we outline the issues that must be considered,
and the criteria that would need to be satisfied, for an imaging end-point to supplement
or potentially replace RECIST- defined tumour status as a phase II clinical trial
end-point. The key criteria proposed to judge the utility of a new end-point primarily
relate to its ability to accurately and reproducibly predict the eventual phase III
end-point for treatment effect, which is usually assessed by a difference between
two arms on progression free or overall survival, both at the patient and more importantly
at the trial level. As will be demonstrated, the level of evidence required to formally
and fully validate a new imaging marker as an appropriate end-point for phase II trials
is substantial. In many cases, this level of evidence will only become available by
conducting a series of coordinated prospectively designed multicentre clinical trials
culminating in a formal meta-analysis. We also include a discussion of situations
where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate
inevitable real-world feasibility constraints.
Keywords
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Article info
Publication history
Published online: December 17, 2008
Accepted:
October 29,
2008
Received:
October 17,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
