title: What can we learn from the time course of untreated and partially treated community-onset Streptococcus pneumoniae pneumonia? A clinical perspective on superiority and noninferiority trial designs for mild community-acquired pneumonia.
abstract: There are no well-designed placebo-controlled clinical trials in the recent era that precisely define the magnitude of the drug effect of antimicrobial therapy for mild community-acquired pneumonia (CAP). However, there is evidence that ineffective therapies, selected on the basis of the ratio of 24-h area under the concentration curve to minimum inhibitory concentration, associated with a discordant (nonsusceptible in vitro) specific agent (or no therapy) for mild CAP due to Streptococcus pneumoniae are associated with increased risk of progression to serious CAP. The relatively high rate of clinical success associated with appropriate antimicrobial treatment of mild CAP renders a standard outcome measure of clinical success an unlikely way to differentiate new agents. However, there may be an advantage in composite outcome assessments for mild CAP. Composite-outcomes end points that include time to resolution of morbidity, the use of patient reported-outcomes instruments, and biomarkers are recommended for future studies. Because the composite rate of success in recent randomized clinical trials exceeds 90%, it would seem that a noninferiority margin of 10% is reasonable for trials for mild CAP.
authors.affiliation: Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA. FileT@summa-health.org
authors.forename: Thomas M
authors.initials: TM
authors.lastname: File
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Schentag
mesh_terms: D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D018450:Disease Progression; D006801:Humans; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D013997:Time Factors; D016896:Treatment Outcome