Advisory Committee Hears Plea for Guidance in Pneumonia Trials

A member of the Infectious Diseases Society of America is telling the FDA the situation with community-acquired pneumonia (CAP) constitutes “a public health emergency” requiring urgent action to remove “uncertainty from the design of clinical trials” for the disease.

David Gilbert, chief of infectious diseases at Providence Portland Medical Center in Oregon and a member of the society, spoke of the urgency to “break the logjam” on CAP trial designs during a presentation last week to the FDA’s Anti-Infective Drugs Advisory Committee.

CAP trial designs may demonstrate the superiority of the investigational drug to standard antibiotics or, in case of a noninferiority design, a substantial treatment effect that justifies approval of a new drug, Gilbert said. Quantitative endpoints can be used to prove such substantive treatment effects, he added.

However, noninferiority designs “should be avoided if possible because they share many of the inherent dangers of historically controlled trials,” Tom Fleming, professor of biostatistics at the University of Washington, said.

Although valid noninferiority trials of CAP are possible under certain circumstances, Fleming recommended they have all-cause mortality endpoints and recruit from a population with at least 15 percent mortality and that clinical investigators confirm the presence of pneumococcal pneumonia-like disease through a microbiological examination.