Characterizing systematic challenges in sample size determination for sepsis trials.
Characterizing systematic challenges in sample size determination for sepsis trials.
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描述脓毒症试验样本量确定中的系统挑战。
DOI：
10.1007/s00134-022-06691-4
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发表时间：
2022
影响因子：
38.9
通讯作者：
Cook,DeborahJ
中科院分区：
文献类型：
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作者：
Tran,Alexandre;Fernando,ShannonM;Rochwerg,Bram;Seymour,ChristopherW;Cook,DeborahJ
亲爱的编辑，随机对照试验（RCT）被认为是比较健康干预措施的最高水平的证据[1]。然而，试验结果的推断取决于样本量确定期间的临床假设。具有二元结局的优效性试验的样本量计算包括[1]：（a）对照组的预期事件发生率（基线风险），（B）干预的目标差异（绝对或相对风险降低），以及（c）预期I类（p值）和II类错误（把握度）[1]。然而，许多样本量计算是基于对基线风险和风险降低的不合理假设[2]。目标差异应通过现有文献了解，并且对患者很重要[1]。此外，预后或预测富集策略可用于分别告知基线风险或风险降低的更精确估计[3]。生存脓毒症运动（SCC）指南[4]强调了循证方法对早期识别和管理的重要性。尽管对许多干预措施进行了评价，以改善脓毒症患者的结局，但很少有临床试验显示可重现的获益[5]。为了了解脓毒症试验的样本量方法，我们对2000年或以后发表的评估干预措施以降低脓毒症成人死亡率的RCT进行了系统评价。详细的方法和结果见在线补编。我们纳入了60项RCT（57，201例患者），最常见的是欧洲（33%），
Dear Editor, Randomized controlled trials (RCTs) are considered the highest level of evidence for comparing health interventions [1]. However, inferences from trial results depend on clinical assumptions made during sample size determination. The sample size calculation for a superiority trial with a binary outcome incorporates [1]:(a) expected event rate in the control group (baseline risk),(b) target difference by the intervention (absolute or relative risk reduction), and (c) desired type I (p-value) and type II error (power)[1]. However, many sample size calculations are based on implausible assumptions about baseline risk and risk reduction [2]. The target difference should be informed by existing literature and important to patients [1]. Furthermore, prognostic or predictive enrichment strategies can be employed to inform more precise estimates of baseline risk or risk reduction, respectively [3].The Surviving Sepsis Campaign (SCC) Guidelines [4] highlight the importance of an evidence-based approach to early identification and management. Despite the evaluation of many interventions to improve outcomes for septic patients, few have shown reproducible benefit in clinical trials [5]. To understand sample size methodology for sepsis trials, we conducted a systematic review of RCTs evaluating interventions to reduce mortality in adults with sepsis, published in the year 2000 or later. The detailed methodology and results are provided in the online supplement. We included 60 RCTs (57,201 patients), most commonly based in Europe (33%) and