Escalation With Overdose Control (EWOC) version 2.0 is a publicly available freeware that uses Bayesian methods in a dose escalation scheme to assign dose levels sequentially to patients in cancer phase I clinical trials. The methodology is based on the optimal Bayesian-feasible procedure, which is designed to approach the maximum tolerated dose as fast as possible while controlling the probability of overdosing patients. This article describes the methodology as well as the development of the application program. Features of EWOC 2.0 are demonstrated.
RogatkoABabbJSTighiouartMKhuriFRHudesG. New paradigm in dose-finding trials: patient-specific dosing and beyond phase I. Clin Cancer Res. 2005;11:5342–5346.
2.
O'QuigleyJPepeMFisherL. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics. 1990;46:33–48.
3.
EichhornBHZacksS. Sequential search of an optimal dosage, I. J Am Stat Assoc. 1973;68:594–598.
RogatkoATighiouartMXuZ. Escalation With Overdose Control. Version 2.0. Available at: http://sisyphus.emory.edu/ewoc.html. Accessed January 12, 2006.
6.
WooleyPVScheinPS. Methods Cancer Research. New York, NY: Academic Press; 1979.
7.
BabbJRogatkoAZacksS. Cancer phase I clinical trials: efficient dose escalation with overdose control. Stat Med. 1998;17:1103–1120.
8.
RosenbergerWFHainesLM. Competing designs for phase I clinical trials: a review. Stat Med. 2002;21:2757–2770.
9.
TighiouartMRogatkoABabbJS. Flexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control. Stat Med. 2005;24:2183–2196.
10.
SpiegelhalterDJThomasABestNG. WinBUGS Version 1.2 User Manual. Cambridge, UK: MRC Biostatistics Unit; 1999.
11.
RosenbergerWFCanfieldGCPerevozskayaIHainesLMHausnerP. Development of interactive software for Bayesian optimal phase I clinical trial design. Drug Inf J. 2005;39:89–98.
12.
WhiteheadJPattersonSWebberDFrancisSZhouY. Easy-to-implement Bayesian methods for dose-escalation studies in healthy volunteers. Biostatistics. 2001;2:47–61.
PattersonTNL. On some Gauss and Lobatto based integration formulae. Math Comput. 1968;22:877–881.
15.
PattersonTNL. The optimum addition of points to quadrature formulae, errata. Math Comput. 1969;23:877–881.
16.
BabbJRogatkoA. Bayesian methods for cancer phase I clinical trials. In: GellerN, ed. Contemporary Biostatistical Methods in Clinical Trial. New York, NY: Marcel Dekker; 2004:1–39.
17.
HainesLMPerevozskayaIRosenbergerWF. Bayesian optimal designs for phase I clinical trials. Biometrics. 2003;59:591–600.
18.
TighiouartMRogatkoA. Dose finding in oncology—parametric methods. In: TingN, ed. Dose Finding in Drug Development. New York, NY: Springer; 2006:59–72.