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[JAMA在线发表]:ECMO治疗严重ARDS随机临床试验的事后Bayesian分析
2018年10月29日 时讯速递, 进展交流 暂无评论

Special Communication

October 22, 2018

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome and Posterior Probability of Mortality Benefit in a Post Hoc Bayesian Analysis of a Randomized Clinical Trial

Ewan C. Goligher, George Tomlinson, David Hajage, et al

JAMA. Published online October 22, 2018.

doi:10.1001/jama.2018.14276

Importance 背景

Bayesian analysis of clinical trial data may provide useful information to aid in study interpretation, especially when trial evidence suggests that the benefits of an intervention are uncertain, such as in a trial that evaluated early extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS).

临床试验数据的Bayseian分析能够提供有用信息,帮助解读研究结果,尤其当试验证据提示干预措施疗效并不明确时,如评价ECMO治疗严重ARDS的一项临床试验。

Objective 目的

To demonstrate the potential utility of Bayesian analyses by estimating the posterior probability, under various assumptions, that early ECMO was associated with reduced mortality in patients with very severe ARDS in a randomized clinical trial (RCT).

显示在各种不同假设的情况下,Bayesian分析评估事后概率(即一项RCT中早期ECMO伴随最严重ARDS患者病死率降低)的可能用途。

Design and Evidence 设计及证据

A post hoc Bayesian analysis of data from an RCT (ECMO to Rescue Lung Injury in Severe ARDS [EOLIA]) that included 249 patients with very severe ARDS who had been randomized to receive early ECMO (n = 124; mortality at 60 days, 35%) vs initial conventional lung-protective ventilation with the option for rescue ECMO (n = 125, mortality at 60 days, 46%). The trial was designed to detect an absolute risk reduction (ARR) of 20%, relative risk (RR) of 0.67. Statistical prior distributions were specified to represent varying levels of preexisting enthusiasm or skepticism for ECMO and by Bayesian meta-analysis of previously published studies (with downweighting to account for differences and quality between studies). The RR, credible interval (CrI), ARR, and probability of clinically important mortality benefit (varying from RR less than 1 to RR less than 0.67 and ARR from 2% or more to 20% or more) were estimated with Bayesian modeling.

对以下RCT结果进行事后Bayesian分析。EOLIA试验是一项随机对照临床试验,纳入249名病情非常严重的ARDS患者,并随机分为早期ECMO组(n = 124;60天病死率35%)与初始传统肺保护通气且后期可进行挽救性ECMO组(n = 125;60天病死率40%)。试验旨在发现绝对危险度(ARR)降低20%,相对危险度(RR)为0.67。采用统计先验分布以代表对ECMO疗效不同程度的热衷或怀疑,以及对于既往发表研究的Bayesian meta分析(降低权重以校正不同研究间的差异及质量)。通过Bayesian模型估测RR,可靠区间(CrI),ARR及临床重要的病死率获益概率(从RR < 1到RR < 0.67,且从ARR> 2%到> 20%)。

Findings 结果

Combining a minimally informative prior distribution with the findings of the EOLIA trial, the posterior probability of RR less than 1 for mortality at 60 days after randomization was 96% (RR, 0.78 [95% CrI, 0.56-1.04]); the posterior probability of RR less than 0.67 was 18%, the probability of ARR of 2% or more was 92%, and the probability of ARR of 20% or more was 2%. With a moderately enthusiastic prior, equivalent to information from a trial of 264 patients with an RR of 0.78, the estimated RR was 0.78 (95% CrI, 0.63-0.96), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 8%, the probability of ARR of 2% or more was 97%, and the probability of ARR of 20% or more was 0%. With a strongly skeptical prior, equivalent to information from a trial of 264 patients with an RR of 1.0, the estimated RR was 0.88 (95% CrI, 0.71-1.09), the probability of RR less than 1 was 88%, the probability of RR less than 0.67 was 0%, the probability of ARR of 2% or more was 78%, and the probability of ARR of 20% or more was 0%. If the prior was informed by previous studies, the estimated RR was 0.71 (95% CrI, 0.55-0.94), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 48%, the probability of ARR of 2% or more was 98%, and the probability of ARR of 20% or more was 4%.

综合先验分布结果与EOLIA试验发现,随机分组后60天病死率RR < 1的事后概率为96% (RR, 0.78 [95% CrI, 0.56-1.04];RR < 0.67的事后概率为 18%,ARR > 2%的概率为92%,ARR > 20%的概率为2%。对于中等程度的热衷者,相当于纳入264名患者的临床试验结果RR为0.78,估计 RR 为 0.78 (95% CrI, 0.63-0.96),RR < 1的概率为 99%,RR < 0.67的概率为8%,ARR > 2%的概率为97%,ARR > 20%的概率为 0%。对于强烈怀疑者,相当于纳入264名患者的临床试验结果RR为1.0,估测的RR为0.88 (95% CrI, 0.71-1.09),RR < 1的概率为 88%,RR < 0.67的概率为0%,ARR > 2%的概率为78%,ARR > 20%的概率为0%。如果得知既往研究结果,估测RR为 0.71 (95% CrI, 0.55-0.94),RR < 1的概率为 99%,RR < 0.67的概率为48%,ARR >2%的概率为98%,ARR > 2%的概率为4%。

Conclusions and Relevance 结论及意义

Post hoc Bayesian analysis of data from a randomized clinical trial of early extracorporeal membrane oxygenation compared with conventional lung-protective ventilation with the option for rescue extracorporeal membrane oxygenation among patients with very severe acute respiratory distress syndrome provides information about the posterior probability of mortality benefit under a broad set of assumptions that may help inform interpretation of the study findings.

随机临床试验比较了早期ECMO与传统肺保护性通气策略(可选挽救性ECMO)对病情极为危重ARDS患者预后的影响。对这一研究结果的事后Bayesian分析能够在更宽泛假设的前提下,对病死率获益的事后概率提供信息,有助于研究结果的解读。

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