CYTEL SOFTWARE CORPORATION — Department of Health and Human Services SBIR Phase II: The Phase II SBIR contract proposal addresses a problem of fundamental importance for the

Description

The Phase II SBIR contract proposal addresses a problem of fundamental importance for the design and analysis of Phase 3 randomized clinical trials. Over the past decade the design of such trials has been complicated by the desire to ask more than one question, within a single trial, concerning the efficacy and safety of a new therapeutic agent. For example, whereas the large phase II trials conducted in the 80s and 90s were typically two-arm tirals involving a single endpoint, it is now common to include two or more dose groups of the experimental therapy along with an active comparator and possibly placebo as well. Moreover, owing to the complex etiology of many chronic conditions, it is customary to attempt to make multiple claims of efficacy across several endpoints. As a result, contemporary clinical trials often involve multiple hierarchical objectives with logical relationships among them which are such that testing for some objective is conditional on the positive or negative outcome of the test on another objective. It is a regulatory requirement that the analysis of data from such trials, where multiple claims of efficacy may be made in teh product label, must be handled by multiple comparison procedures that guarantee strong control of the family wise error rate (FWER). Commercial grade, validated software to perform sample size calculations or generate multiplicity adjusted inferences is, however, limited. The overall goal of this project is to develop a professional, robust and commercially viablesoftware package for handling multiplicity at both the design and analysis phases of a clinical trial. The software will address the following three major sources of multiplicity: hypothesis testing of mulitple treatment arms versus a common control, hypothesis testig with respect to multiple endpoints, and group sequential testing of the same hypothesis repeatedly over information time. The software so developed will be fully integrated into Cytel's East software system.