ABSTRACT
The evolution of clinical trial design in febrile neutropenia has paralleled the evolution of the antibiotic armamentarium. The initial study establishing the relationship between neutrophil count and infection focused on mortality, a common event in the 1960s before modern antibiotics were available.1 An early trial of carbenicillin, which documented the need for empiric therapy at the onset of infection, was a ‘before-and-after’ design.2 Results from the introduction of empiric therapy with an antipseudomonal penicillin were compared with historical data. In this case, the mortality rate was so high prior to empiric and specific anti-pseudomonal therapy, and the clinical experience so consistent from one institution to the next, that a randomized trial was not required to demonstrate efficacy. As the options for antibiotic therapy have increased, increasingly stronger evidence from rigorously designed clinical trials has been required to change practice. Currently, clinical trialists are challenged to design within-antibiotic-class comparisons examining subtle differences among very similar agents.3 Despite over four decades of experience in clinical trials in febrile neutropenia, many issues remain unresolved, and new controversies have arisen with
advances in medicine and healthcare policy. In this chapter, we describe the current state of the art in design of clinical trials of febrile neutropenia, and discuss the controversies that challenge us in the field today.
