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2017 ; 26
(5
): 2376-2388
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Unbiased estimation for response adaptive clinical trials
#MMPMID26265771
Bowden J
; Trippa L
Stat Methods Med Res
2017[Oct]; 26
(5
): 2376-2388
PMID26265771
show ga
Bayesian adaptive trials have the defining feature that the probability of
randomization to a particular treatment arm can change as information becomes
available as to its true worth. However, there is still a general reluctance to
implement such designs in many clinical settings. One area of concern is that
their frequentist operating characteristics are poor or, at least, poorly
understood. We investigate the bias induced in the maximum likelihood estimate of
a response probability parameter, p, for binary outcome by the process of
adaptive randomization. We discover that it is small in magnitude and, under mild
assumptions, can only be negative - causing one's estimate to be closer to zero
on average than the truth. A simple unbiased estimator for p is obtained, but it
is shown to have a large mean squared error. Two approaches are therefore
explored to improve its precision based on inverse probability weighting and
Rao-Blackwellization. We illustrate these estimation strategies using two
well-known designs from the literature.
|*Bias
[MESH]
|Adaptive Clinical Trials as Topic/*methods
[MESH]