Response Adjusted for Days of Antibiotic Risk (RADAR) : evaluation of a novel method to compare strategies to optimise antibiotic use

Abstract

OBJECTIVES: The Response Adjusted for Days of Antibiotic Risk (RADAR)-statistic was proposed to improve 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 (BL, n=656) was non-inferior to fluoroquinolone monotherapy (FQL, n=888) for moderately-severe community-acquired pneumonia (CAP) patients. METHODS: Patients were ranked according to clinical outcome, using five or eight categories, and antibiotic use. RADAR was calculated as the probability that the BL group had a more favourable ranking than the FQL group. To investigate the sensitivity of RADAR to detrimental clinical outcome we simulated increasing rates of 90-day mortality in the BL group and performed the RADAR and non-inferiority analysis. RESULTS: The RADAR of the BL-group compared to the FQL group was 60.3% (95% confidence interval 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%) using eight clinical outcome categories, all in favour of BL. 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 BL-group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the BL-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 BL over FQL therapy for CAP. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes.