title: Historical and regulatory perspectives on the treatment effect of antibacterial drugs for community-acquired pneumonia.
abstract: A noninferiority margin based on the treatment effect of antibacterial drugs is required for noninferiority studies of community-acquired pneumonia. A quantitative estimate of treatment effect is generally determined from placebo-controlled trials, but, since the mid-to-late 1930s, no studies have compared outcomes for patients who received placebo (or no specific therapy) with those for patients who received an antibacterial drug for treatment of community-acquired pneumonia. In this article, early controlled studies, as well as observational data, are reviewed, and the beneficial effect of antibacterial drugs on mortality rates among patients with pneumococcal pneumonia is demonstrated. However, because these data were obtained in the early 20th century, several important factors have changed, including patient populations, the etiological agents of pneumonia, and medical standards of care. Thus, the applicability of these studies to the determination of a noninferiority margin for contemporary trials for community-acquired pneumonia remains in question.
authors.affiliation: US Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Office of Antimicrobial Products, Silver Spring, Maryland 20993, USA. mary.singer@fda.hhs.gov
authors.forename: M
authors.initials: M
authors.lastname: Singer
authors.forename: S
authors.initials: S
authors.lastname: Nambiar
authors.forename: T
authors.initials: T
authors.lastname: Valappil
authors.forename: K
authors.initials: K
authors.lastname: Higgins
authors.forename: S
authors.initials: S
authors.lastname: Gitterman
mesh_terms: D000900:Anti-Bacterial Agents / Q000266:history / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000266:history*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000266:history / Q000401:mortality; D049673:History, 20th Century; D006801:Humans; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000266:history / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents