Department of Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA; Department of Orthopaedic Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Department of Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
World Neurosurg. 2022 Aug;164:135-142. doi: 10.1016/j.wneu.2022.04.121. Epub 2022 May 5.
Randomized controlled trials (RCTs) have come under scrutiny due to a frequent lack of reproducibility, due in part to shortcomings of the common P < 0.05 threshold for significance. Here, we utilize fragility indices to assess the statistical robustness of RCTs evaluating low-dose ketamine during scoliosis surgery to reduce opioid tolerance and postoperative pain.
RCTs evaluating outcomes after intraoperative ketamine infusion in adolescent idiopathic scoliosis patients were included. Relevant outcomes included pain, opioid consumption, quality of life, anesthesia, sedation, adverse effects, and length of stay. The dichotomous fragility index or continuous fragility index (FI or CFI) was determined by manipulating each outcome event until reversal of significance (a = 0.05) was achieved. The corresponding fragility quotients were calculated by dividing the FI or CFI by the sample size.
Of 27 studies screened, 6 studies (61 outcome events) were included. The median FI for dichotomous events was 2.0 (fragility quotient = 0.045), suggesting that altering the outcome of only 2 patients (or 4.5 out of 100) would reverse trial significance. For continuous events, altering the treatment of only 6 patients (or 14.1 out of 100) would reverse significance. Outcome events that were originally reported as significant (P < 0.05) were considerably more fragile (FI = 1.5; CFI = 3.5) than events that were reported as nonsignificant (FI = 2.0; CFI = 7.0).
While evidence for ketamine use is promising, our fragility analysis suggests that RCT findings may be underpowered in some cases. Given the importance of RCTs in clinical decision-making, fragility indices should be reported alongside P values to indicate the strength of statistical findings.
由于缺乏可重复性，随机对照试验（RCT）受到了频繁的审查，部分原因是常见的 P < 0.05 显著性阈值存在缺陷。在这里，我们利用脆弱性指数来评估评估脊柱侧凸手术中低剂量氯胺酮降低阿片类药物耐受和术后疼痛的 RCT 的统计学稳健性。
纳入评估青少年特发性脊柱侧凸患者术中氯胺酮输注后结局的 RCT。相关结局包括疼痛、阿片类药物消耗、生活质量、麻醉、镇静、不良反应和住院时间。通过操纵每个结局事件，直到达到显著性逆转（a = 0.05）来确定二分类脆弱性指数或连续脆弱性指数（FI 或 CFI）。脆弱性比率通过将 FI 或 CFI 除以样本量来计算。
在筛选出的 27 项研究中，有 6 项研究（61 项结局事件）入选。二分类事件的中位数 FI 为 2.0（脆弱性比率= 0.045），这表明仅改变 2 名患者（或 100 名中的 4.5 名）的结局就会使试验的显著性逆转。对于连续事件，仅改变 6 名患者（或 100 名中的 14.1 名）的治疗就会使显著性逆转。最初报告为显著（P < 0.05）的结局事件比报告为不显著（P > 0.05）的事件更加脆弱（FI = 1.5；CFI = 3.5）。
虽然氯胺酮使用的证据很有前景，但我们的脆弱性分析表明，在某些情况下，RCT 的发现可能没有足够的效力。鉴于 RCT 在临床决策中的重要性，除了 P 值外，还应报告脆弱性指数，以表明统计结果的强度。
