The Integrated Web Portal for Escalation with Overdose Control (EWOC)

Wang, Haibin

doi:10.2174/1874-431120130427001

Cited by 1 publication

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References 4 publications

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“…The method is flexible enough to allow prior information about the drug from laboratory or animal studies to be incorporated in the model, makes use of all the information available at the time of each dose assignment, controls the probability of overdosing patients at each stage, allows the estimation of the precision of the MTD, is optimally Bayesian feasible [ 4 ], produces a sequence of doses that converges in probability to the MTD [ 4 ], is coherent [ 5 , 6 ], and accounts for patients' pre-treatment characteristics [ 7 – 9 ]. EWOC can be implemented with the user friendly software EWOC [ 10 , 11 ] or WinBUGS [ 12 ] for general class of prior distributions [ 13 ], or ordinal toxicity grades [ 14 ]. EWOC allows flexible patient enrollment, and conforms to the ethical goal of maximizing the number of patients receiving optimal doses.…”

Section: Introductionmentioning

confidence: 99%

Escalation with Overdose Control is More Efficient and Safer than Accelerated Titration for Dose Finding

Rogatko

Tighiouart

Piantadosi

2015

Entropy

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The standard 3 + 3 or “modified Fibonacci” up-and-down (MF-UD) method of dose escalation is by far the most used design in dose-finding cancer trials. However, MF-UD has always shown inferior performance when compared with its competitors regarding number of patients treated at optimal doses. A consequence of using less effective designs is that more patients are treated with doses outside the therapeutic window. In June 2012, the U S Food and Drug Administration (FDA) rejected the proposal to use Escalation with Overdose Control (EWOC), an established dose-finding method which has been extensively used in FDA-approved first in human trials and imposed a variation of the MF-UD, known as accelerated titration (AT) design. This event motivated us to perform an extensive simulation study comparing the operating characteristics of AT and EWOC. We show that the AT design has poor operating characteristics relative to three versions of EWOC under several practical scenarios. From the clinical investigator's perspective, lower bias and mean square error make EWOC designs preferable than AT designs without compromising safety. From a patient's perspective, uniformly higher proportion of patients receiving doses within an optimal range of the true MTD makes EWOC designs preferable than AT designs.

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