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bioRxiv · 10.1101/107300

Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel method to analyze antibiotic stewardship interventions

Schweitzer, V. A.·van Smeden, M.·Postma, D. F.·Oosterheert, J. J.·Bonten, M. J. M.·van Werkhoven, C. H.
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Abstract

OBJECTIVESThe Response Adjusted for Days of Antibiotic Risk (RADAR)-statistic was proposed to improve efficiency of antibiotic stewardship trials. We studied the behavior 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.\n\nMETHODSPatients 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 favorable 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.\n\nRESULTSThe 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 favor of BL. Sample sizes for RADAR were 250 and 580 patients per study arm using five or eight clinical outcome categories, respectively, reflecting 38% and 89% of the original non-inferiority sample size calculation. 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.\n\nCONCLUSIONSRADAR favored BL over FQL therapy for CAP. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes.

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Schweitzer, V. A., van Smeden, M., Postma, D. F., Oosterheert, J. J., Bonten, M. J. M., van Werkhoven, C. H.. 2017-02-12. Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel method to analyze antibiotic stewardship interventions. https://doi.org/10.1101/107300

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