Methodology for Clinical Trials Involving Patients with Cancer Who Have Febrile Neutropenia: Updated Guidelines of the Immunocompromised Host Society/ Multinational Association for Supportive Care in Cancer, with Emphasis on Outpatient Studies

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy. Since the 1970s, many clinical trials have been con-ducted to compare different antibiotic regimens as in-itial therapy for febrile neutropenic episodes in patients with cancer. The methodology for these trials has varied tremendously, especially with regard to the issues o