Concepts in design of comparative clinical trials of antifungal therapy inneutropenic patients

Fundamental to the successful implementation of antifungal compounds in neu tropenic patients is the appropriate design of comparative clinical trials investigating their safety and efficacy. The key elements of comparative cl inical trial design include issues of enrolment, stratification, randomizat ion, blinding, administration of study drugs, monitoring of drug toxicity, definitions, and key statistical elements of end points, sample size, and t ools for data analysis. The initial selection of compounds and the timing o f initiation of antifungal therapy in comparative clinical trials are predi cated to a large degree on the in vitro and in vivo activities, plasma phar macokinetics, profiles of safety and toxicity of the study drugs. Phase I a nd II studies have a critical role in designing comparative clinical trials of antifungal therapy by providing data on safety, tolerance, and plasma p harmacokinetics of the investigational agent. As new antifungal agents are developed in response to the challenge of invasive fungal infections in imm unocompromised patients with cancer, thoughtfully designed and carefully im plemented clinical trials will be essential in determining the future utili ty of these promising compounds. (C) 2000 Elsevier Science B.V. and Interna tional Society of Chemotherapy. All rights reserved.