Sluis Wouter M, de Jonge Jeroen C, Reinink Hendrik, Wilson Alastair, Woodhouse Lisa J, Dawson Jesse, Lees Kennedy R, Bath Philip M, van der Worp Hendrik Bart
Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
Eur Stroke J. 2025 Feb 19:23969873251320207. doi: 10.1177/23969873251320207.
The modified Rankin Scale (mRS) is the most frequently used primary outcome measure in acute stroke research despite significant interobserver variability in assigning grades. We assessed the use of central blinded adjudication of the mRS based on a video recording of an interview in the PRECIOUS trial.
PRECIOUS was an international, randomized, open-label, clinical trial with blinded outcome assessment of preventive treatment with metoclopramide, paracetamol, and ceftriaxone in elderly patients with acute stroke. Trained local investigators interviewed patients or their representatives and graded functional outcome at 90 days after stroke with the mRS. In each participating country, a video recording of the interview was assessed by three blinded, independent adjudicators. The primary outcome of the present substudy was interobserver agreement between the local mRS score and the median score of the three central adjudicators for patients alive at 90 days, assessed with Cohen's kappa and quadratic weighted kappa statistics. The difference between treatment effect estimates based on local and central adjudication was a secondary outcome.
Of 1493 patients enrolled in PRECIOUS, 1471 were included in this analysis. At 90 days, 1117 patients (75.9%) were alive and had both a central and local assessment; 28 participants did not have a central mRS score. Interobserver agreement was seen in 829 (74.2%) patients and was substantial (kappa of 0.68; 95% CI 0.65-0.71). Disagreement occurred more often in patients with a central mRS score of 0-2 (OR 2.24; 95% CI 1.14-4.24). Treatment effects were neutral for all three study drugs and did not differ between central and local adjudication.
Central adjudication of the mRS based on a video recording is feasible in a large international, randomized stroke trial. This ensures blinding of the outcome assessment. In this neutral trial, the impact of central adjudication on the precision of effect size estimates could not be assessed.
改良Rankin量表(mRS)是急性中风研究中最常用的主要结局指标,尽管在评定等级时观察者间存在显著差异。我们在PRECIOUS试验中基于访谈视频记录评估了mRS的中央盲法判定的应用情况。
PRECIOUS是一项国际、随机、开放标签的临床试验,对老年急性中风患者使用甲氧氯普胺、对乙酰氨基酚和头孢曲松进行预防性治疗的结局评估采用盲法。经过培训的当地研究人员对患者或其代表进行访谈,并在中风后90天用mRS对功能结局进行评分。在每个参与国家,由三名盲法、独立的判定人员对访谈视频记录进行评估。本亚组研究的主要结局是90天时存活患者的当地mRS评分与三名中央判定人员的中位数评分之间的观察者间一致性,采用Cohen's kappa统计量和二次加权kappa统计量进行评估。基于当地判定和中央判定的治疗效果估计值之间的差异是次要结局。
PRECIOUS试验纳入的1493例患者中,1471例纳入本分析。在90天时,1117例患者(75.9%)存活,且有中央和当地评估;28例参与者没有中央mRS评分。829例(74.2%)患者存在观察者间一致性,且一致性程度较高(kappa为0.68;95%CI 0.65 - 0.71)。中央mRS评分为0 - 2分的患者中分歧更常见(OR 2.24;95%CI 1.14 - 4.24)。三种研究药物的治疗效果均为中性,中央判定和当地判定之间无差异。
在大型国际随机中风试验中,基于视频记录对mRS进行中央判定是可行的。这确保了结局评估的盲法。在这项中性试验中,无法评估中央判定对效应大小估计精度的影响。