From the Department of Neurosurgery (A.T.B., T.P., J.T., F.S.V.), and Center for Health Data Science and Analytics (A.P.P., G.B., F.S.V.), Houston Methodist, TX; Weill Cornell Medical College (G.B., F.S.V.), New York, NY; Houston Methodist Academic Institute (G.B., F.S.V.), TX; Division of Brain Injury Outcomes (W.C.Z., D.H.), Johns Hopkins University, Baltimore, MD; and Department of Neurological Surgery (I.A.), University of Chicago Medicine and Biological Sciences, IL.
Neurology. 2023 Oct 17;101(16):e1614-e1622. doi: 10.1212/WNL.0000000000207735. Epub 2023 Sep 8.
Bayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional value-based binary cutoffs. We conducted an exploratory post hoc Bayesian reanalysis of the minimally invasive surgery with thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE-3) trial and derived probabilities of potential intervention effect on functional and survival outcomes.
MISTIE-3 was a multicenter phase 3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. Five hundred and six adults (18 years or older) with spontaneous, nontraumatic, supratentorial ICH of ≥30 mL were randomized to receive either the MISTIE intervention (n = 255) or standard medical care (n = 251). We provide Bayesian-derived estimates of the effect of the MISTIE intervention on achieving a good 365-day modified Rankin Scale score (mRS score 0-3) as relative risk (RR) and absolute risk difference (ARD), and the probabilities that these treatment effects are greater than prespecified thresholds. We used 2 sets of prior distributions: (1) reference priors, including minimally informative, enthusiastic, and skeptical priors, and (2) data-derived prior distribution, using a hierarchical random effects model. We additionally evaluated the potential effects of the MISTIE intervention on 180-day and 30-day mRS and 365-, 180-, and 30-day mortality using data-derived priors.
The Bayesian-derived probability that MISTIE intervention has any beneficial effect (RR >1) on achieving a good 365-day mRS score was 70% using minimally informative prior, 87% with enthusiastic prior, 68% with skeptical prior, and 73% with data-derived prior. However, these probabilities were ≤55% for RR >1.10 and 0% for RR >1.52 across a range of priors. The probabilities of achieving RR >1 for 180- and 30-day mRS scores are 65% and 80%, respectively. Furthermore, the probabilities of achieving RR <1 for 365-, 180-, and 30-day mortality are 93%, 98%, and 99%, respectively.
Our exploratory analyses indicate that across a range of priors, the Bayesian-derived probability of MISTIE intervention having any beneficial effect on 365-day mRS for patients with ICH is between 68% and 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects.
ClinicalTrials.gov/ct2/show/NCT01827046.
This study provides Class II evidence that minimally invasive surgery (MIS) + recombinant tissue plasminogen activator (rt-PA) does not significantly improve functional outcome in patients with ICH. However, this study lacks the precision to exclude a potential benefit of MIS + rt-PA.
贝叶斯分析随机对照试验（RCT）可以扩展试验数据的价值，超出基于传统价值的二元截止值的解释范围。我们对微创血肿清除术（MISTIE）试验进行了最小侵入性手术与溶栓治疗脑出血（ICH）清除的探索性事后贝叶斯重新分析，并得出了潜在干预对功能和生存结果的影响的概率。
MISTIE-3 是一项多中心 3 期 RCT，旨在评估 MISTIE 干预的疗效和安全性。506 名成年人（18 岁或以上）自发性、非外伤性、幕上 ICH 容积≥30ml 被随机分为接受 MISTIE 干预（n=255）或标准医疗护理（n=251）。我们提供了贝叶斯估计的 MISTIE 干预对实现 365 天改良 Rankin 量表评分（mRS 评分 0-3）的效果的估计，即相对风险（RR）和绝对风险差异（ARD），以及这些治疗效果大于预定阈值的概率。我们使用了 2 组先验分布：（1）参考先验分布，包括最小信息量、热情和怀疑先验分布，以及（2）使用分层随机效应模型的数据衍生先验分布。我们还使用数据衍生的先验分布评估了 MISTIE 干预对 180 天和 30 天 mRS 和 365 天、180 天和 30 天死亡率的潜在影响。
使用最小信息量先验，贝叶斯估计的 MISTIE 干预对实现良好 365 天 mRS 评分的任何有益效果（RR>1）的概率为 70%，使用热情先验为 87%，使用怀疑先验为 68%，使用数据衍生先验为 73%。然而，这些概率对于 RR>1.10 和 RR>1.52 均小于 55%。对于 RR>1.10 和 RR>1.52，365 天和 180 天 mRS 评分的 RR>1 的概率分别为 65%和 80%。此外，对于 RR<1.00，365 天、180 天和 30 天死亡率的概率分别为 93%、98%和 99%。
我们的探索性分析表明，在一系列先验分布中，贝叶斯估计的 MISTIE 干预对 ICH 患者 365 天 mRS 的任何有益效果的概率在 68%至 87%之间。这些分析没有改变基于频率的试验解释。然而，与间接评估治疗效果的频率值不同，这些值只提供任意的二元截止值（如 0.05），贝叶斯框架直接估计潜在治疗效果的概率。
ClinicalTrials.gov/ct2/show/NCT01827046。
本研究提供了 II 级证据，表明微创血肿清除术（MIS）+重组组织型纤溶酶原激活剂（rt-PA）不能显著改善 ICH 患者的功能结局。然而，本研究缺乏排除 MIS+rt-PA 潜在益处的精度。
