Web-EWOC: Interactive web tool for Designing and Conducting Dose Finding Trials in Cancer
Web-EWOC (Escalation with overdose control) provides registered users with web-based calculators, documentation, and stand-alone downloadable application to design and conduct dose finding clinical trials in cancer using the EWOC method. EWOC is a Bayesian adaptive dose finding design that produces consistent sequences of doses while controlling the probability that patients are overdosed. EWOC was the first dose-finding procedure to directly incorporate the ethical constraint of minimizing the chance of treating patients at unacceptably high doses. Its defining property is that the expected proportion of patients treated at doses above the maximum tolerated dose (MTD) is equal to a specified value α, the feasibility bound. This value is selected by the clinician and reflects his/her level of concern about overdosing. Among designs with this defining property, EWOC minimizes the average amount by which patients are underdosed. This means that EWOC approaches the MTD as rapidly as possible, while keeping the expected proportion of patients overdosed less than the value α. As a trial progresses, the dose sequence defined by EWOC approaches the MTD (i.e., the sequence of recommended doses converges in probability to the MTD). Eventually, all patients beyond a certain time would be treated at doses sufficiently close to the MTD (1). When comparing EWOC with alternative phase I design methods, it has been shown that up-and-down designs treated only 35% of patients at optimal dose levels, versus 55% for EWOC, i.e., more patients are treated with doses outside the therapeutic window by up-and-down than by EWOC designs(2). Babb and Rogatko (3) provide a summary of Bayesian phase I design methods and Tighiouart et al. (4) studied the performance of EWOC under a rich class of prior distributions for the MTD. Tighiouart and Rogatko (5) showed that EWOC is coherent. The only requirement to use Web-EWOC is access to a standard web browser. The web interface is implemented using PHP and JQuery. The EWOC algorithm was implemented using open source software R+OpenBUGS and and R+Fortran. All computations are performed on our web server.
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2. Babb J, Rogatko A, Zacks S. Cancer Phase I clinical Trials: efficient dose escalation with overdose control. Stat Med. 1998;17:1103-20.
3. Babb JS, Rogatko A. Patient specific dosing in a cancer phase I clinical trial. Stat Med. 2001;20(14):2079-90.
4. Tighiouart M, Rogatko A, Babb JS. Flexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control. Stat Med. 2005;24(14):2183-96.
5. Tighiouart M, Rogatko A. Dose Finding with Escalation with Overdose Control (EWOC) in Cancer Clinical Trials. Statistical Science 2010;25(2):217-26.