CHUM Research Center, Pavillon S, 850, St-Denis St., Montreal, Quebec, Canada; The Canadian Network for Observational Drug Effect Studies (CNODES), Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine H-485, Montreal, Quebec Canada; University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, Quebec Canada.
Department of Medicine, McGill University, 3605 de la Montagne St., Montreal, Quebec Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Ave W, Montreal, Quebec Canada.
J Clin Epidemiol. 2021 Dec;140:93-100. doi: 10.1016/j.jclinepi.2021.09.002. Epub 2021 Sep 8.
To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD).
Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively.
While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.
评估多潘立酮在帕金森病(PD)患者中的室性心动过速/心源性猝死(VT/SCD)风险。
使用贝叶斯方法,将观察性研究的结果与先验信念相结合,计算与不使用相比,多潘立酮使用时 VT/SCD 的相对风险(RR)增加的后验概率(RR)和危害,定义为风险超过 15%。使用正态分布先验(RR(对数))进行分析:无信息(N(0,10))或信息(N(0.53,179)),来自荟萃分析(OR(95%CI):1.70(1.47-1.97))。进行了敏感性分析:不同先验的强度、不同的先验和贝叶斯荟萃分析。
无信息先验产生的 RR:1.23(95%置信区间(CrI):0.94-1.62),与已发表的频率 RR 相似:1.22(95%CI:0.99-1.50),危害的可能性为 69%。使用权重为 100%、50%和 10%的信息先验,RR 分别为 1.63(1.41-1.88)、1.57(1.31-1.91)和 1.39(1.10-1.93)。相应的危害概率分别为 100%、99%和 94%。
虽然基于无信息先验的频率和贝叶斯方法都无法对多潘立酮在 PD 患者中的心律失常风险得出明确结论,但具有信息先验的贝叶斯分析显示,风险增加的可能性很高,对多种先验敏感性分析具有稳健性。