V A Schweitzer1, M van Smeden2, D F Postma3, J J Oosterheert3, M J M Bonten4, C H van Werkhoven5. 1. Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: V.A.Schweitzer-2@umcutrecht.nl. 2. Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. 3. Departments of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands. 4. Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands. 5. Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: C.H.vanWerkhoven@umcutrecht.nl.
Abstract
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 β-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 β-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 β-lactam group and performed the RADAR and non-inferiority analysis. RESULTS: The RADAR of the β-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 β-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 β-lactam group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the β-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 β-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.
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 β-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 β-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 β-lactam group and performed the RADAR and non-inferiority analysis. RESULTS: The RADAR of the β-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 β-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 β-lactam group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the β-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 β-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.
Authors: Emmanuel Weiss; Jean-Ralph Zahar; Jeff Alder; Karim Asehnoune; Matteo Bassetti; Marc J M Bonten; Jean Chastre; Jan De Waele; George Dimopoulos; Philippe Eggimann; Marc Engelhardt; Santiago Ewig; Marin Kollef; Jeffrey Lipman; Carlos Luna; Ignacio Martin-Loeches; Leonardo Pagani; Lucy B Palmer; Laurent Papazian; Garyphallia Poulakou; Philippe Prokocimer; Jordi Rello; John H Rex; Andrew F Shorr; George H Talbot; Visanu Thamlikitkul; Antoni Torres; Richard G Wunderink; Jean-François Timsit Journal: Clin Infect Dis Date: 2019-11-13 Impact factor: 20.999
Authors: Marlieke E A de Kraker; Harriet Sommer; Femke de Velde; Isaac Gravestock; Emmanuel Weiss; Alexandra McAleenan; Stavros Nikolakopoulos; Ohad Amit; Teri Ashton; Jan Beyersmann; Leonhard Held; Andrew M Lovering; Alasdair P MacGowan; Johan W Mouton; Jean-François Timsit; David Wilson; Martin Wolkewitz; Esther Bettiol; Aaron Dane; Stephan Harbarth Journal: Clin Infect Dis Date: 2018-11-28 Impact factor: 9.079