WEB-TRIAGE An application for patient registration in phase I dose-escalation studies

Phase I clinical trials conducted to find recommended doses for use in later phase studies, employ pre-specified guidelines. These determine what dose to administer to the next subject or group of subjects. “Standard” Phase I trials (in oncology) use what is often called the ‘3+3’ design, where at least 3 patients are treated at each dose level (dose L), by applying the following rules: − If 0 patients experience dose-limiting toxicity (DLT), escalate to dose L+1; − If 2 or more patients experience DLT, de-escalate to level L-1; − If 1 patient experiences DLT, treat 3 more patients at dose level L; E If 1 of 6 experiences DLT, escalate to dose level L+1; E If 2 or more of 6 experiences DLT, de-escalate to level L-1; Most phase I trials in oncology are multi-institutional (MI). Recent research have investigated accrual data from published phase I clinical trials and it emerged that MI Phase I are associated with an increased number of patients and a trend toward increased accrual time 1 . In addition sequential patient accrual is used within and between L to prevent potential DLTs “clustering” and protect patients from undue exposure to toxic dose overshooting. Thus, triage strategies are commonly used to streamline and coordinate accrual. We therefore developed a web-based application (WEB-Triage) to: − design specific study patient registration form; − propose potential candidate for next available “slot” (the Investigator); − reviewing candidates and eventually accept or reject the registration; − opening or closing dose levels by applying the above rules; − manage concurrent dose-escalation clinical trials The application was developed using Microsoft ASP.NET 2.0 and MS SQL Server 2005 on an IIS (version 6.0) Web Server; HTTPS SSL 128/256 bit was used for data-encryption.