Which Trial Do We Need? Optimal Antibiotic Duration for Patients with Sepsis
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Given the potential benefits of shortened antibiotic courses, prior studies comparing shorter versus longer antibiotic courses have typically adopted a non-inferiority design [3,11]. However, in a study of critically ill patients in whom suboptimal treatment could result in death, a non-inferiority trial would pose a serious ethical dilemma - how to select an "acceptable" increased risk of mortality to use as a non-inferiority margin? For these reasons, we have designed a trial that requires shorter antibiotic therapy demonstrate superior clinical outcomes over longer antibiotic therapy, allowing partial/full credit to be awarded based on patient and clinicians' perceptions of outcome importance and severity. Should clinical outcomes be comparable among the study arms, the DOOR/RADAR framework acknowledges potential unmeasured benefits of shorter courses (e.g., reduced costs, unmeasured toxicity, and antibiotic pressures selecting for individual and global microbial resistance) and accordingly assigns superiority to shorter antibiotic courses. The duration of antibiotic therapy reflected in this adjustment would be the actual (rather than assigned) duration, allowing for a pragmatic analysis of the interventions as applied in practice while mitigating differences between intention-to-treat and per-protocol analyses resulting from poor protocol adherence.
Yek, Christina; Lawandi, Alexander; Evans, Scott R.; and Kadri, Sameer S., "Which Trial Do We Need? Optimal Antibiotic Duration for Patients with Sepsis" (2023). GW Authored Works. Paper 2862.
Biostatistics and Bioinformatics