Objectives: The Response Adjusted for Days of Antibiotic Risk (RADAR) statistic was proposed to improve the efficiency of trials comparing antibiotic stewardship strategies to optimize antibiotic use. We studied the behaviour of RADAR in a non-inferiority trial in which a beta-lactam monotherapy strategy (n = 656) was non-inferior to fluoroquinolone monotherapy (n = 888) for patients with moderately severe community-acquired pneumonia.
Methods: Patients were ranked according to clinical outcome, using five or eight categories, and antibiotic use. RADAR was calculated as the probability that the beta-lactam group had a more favourable ranking than the fluoroquinolone group. To investigate the sensitivity of RADAR to detrimental clinical outcome we simulated increasing rates of 90-day mortality in the beta-lactam group and performed the RADAR and non-inferiority analysis.
Results: The RADAR of the b-lactam group compared with the fluoroquinolone group was 60.3% (95% CI 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%) using eight clinical outcome categories, all in favour of beta-lactam. Sample sizes for RADAR were 38% (250/653) and 89% (580/653) of the non-inferiority sample size calculation, using five or eight clinical outcome categories, respectively. With simulated mortality rates, loss of non-inferiority of the beta-lactam group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the beta-lactam group lost superiority at a relative risk of mortality of 1.25 and 1.5, with eight and five clinical outcome categories, respectively.
Conclusions: RADAR favoured beta-lactam over fluoroquinolone therapy for community-acquired pneumonia. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
- Antibiotic stewardship
- Antibiotic use strategies
- Community-acquired pneumonia
- COMMUNITY-ACQUIRED PNEUMONIA