Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
Clin Microbiol Infect. 2017 Dec;23(12):980-985. doi: 10.1016/j.cmi.2017.05.003. Epub 2017 May 10.
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.
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.
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.
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.
为了提高比较抗生素管理策略以优化抗生素使用的试验效率，提出了针对抗生素风险天数调整的反应（RADAR）统计量。我们在一项非劣效性试验中研究了 RADAR 的行为，该试验中，β-内酰胺单药治疗策略（n=656）与氟喹诺酮单药治疗策略（n=888）相比，对于患有中度严重社区获得性肺炎的患者不劣效。
根据临床结局（使用五分类或八分类）和抗生素使用情况对患者进行排名。RADAR 计算为β-内酰胺组的排名优于氟喹诺酮组的概率。为了研究 RADAR 对不良临床结局的敏感性，我们模拟了β-内酰胺组 90 天死亡率增加的情况，并进行了 RADAR 和非劣效性分析。
β-内酰胺组与氟喹诺酮组相比，使用五分类时 RADAR 为 60.3%（95%CI 57.9%-62.7%），使用八分类时为 58.4%（95%CI 56.0%-60.9%），均有利于β-内酰胺。使用五分类和八分类时，RADAR 的样本量分别为非劣效性样本量计算的 38%（250/653）和 89%（580/653）。在模拟死亡率的情况下，β-内酰胺组在常规分析中，相对风险为 1.125 时，失去非劣效性；而使用 RADAR，β-内酰胺组在八分类和五分类时，死亡率的相对风险分别为 1.25 和 1.5 时，失去了优势。
RADAR 支持β-内酰胺治疗社区获得性肺炎优于氟喹诺酮治疗。虽然 RADAR 比传统非劣效性分析需要的患者更少，但该统计对不良结局的敏感性较低。
