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对羟氯喹和阿奇霉素对新冠病毒肺炎患者病毒携带影响的贝叶斯再分析。

A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19.

作者信息

Hulme Oliver James, Wagenmakers Eric-Jan, Damkier Per, Madelung Christopher Fugl, Siebner Hartwig Roman, Helweg-Larsen Jannik, Gronau Quentin F, Benfield Thomas Lars, Madsen Kristoffer Hougaard

机构信息

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

London Mathematical Laboratory, London, United Kingdom.

出版信息

PLoS One. 2021 Feb 19;16(2):e0245048. doi: 10.1371/journal.pone.0245048. eCollection 2021.

Abstract

Gautret and colleagues reported the results of a non-randomised case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors reported that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. In light of criticisms regarding how patients were excluded from analyses, we reanalysed the original data to interrogate the main claims of the paper. We applied Bayesian statistics to assess the robustness of the original paper's claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy was effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We found that the statistical evidence was highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ~11), to moderate when including patients who deteriorated (BF+0 ~4.35), to anecdotal when excluding untested patients (BF+0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ~0.6). The fact that the patient inclusions and exclusions are not well justified nor adequately reported raises substantial uncertainty about the interpretation of the evidence obtained from the original paper.

摘要

高特雷及其同事报告了一项非随机病例系列研究的结果,该研究考察了羟氯喹和阿奇霉素对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)患者上呼吸道病毒载量的影响。作者报告称,羟氯喹(HCQ)具有显著的病毒减少作用,并且HCQ与阿奇霉素联合治疗进一步增强了病毒减少效果。鉴于对患者如何被排除在分析之外存在批评意见,我们重新分析了原始数据,以审视该论文的主要观点。我们应用贝叶斯统计通过测试数据的四种变体来评估原始论文观点的稳健性:1)原始数据;2)包括病情恶化患者的数据;3)包括病情恶化患者且排除对照组中未检测患者的数据;4)包括病情恶化患者且假设未检测患者为阴性的数据。为了探究HCQ单药治疗是否有效,我们对一个假设具有积极效果的模型与一个无效果模型进行了A/B测试。我们发现统计证据对这些数据变体高度敏感。积极效果模型的统计证据范围从原始数据时的强证据(BF+011),到包括病情恶化患者时的中等证据(BF+04.35),到排除未检测患者时的轶事性证据(BF+02),再到假设未检测患者为阳性时的轶事性负面证据(BF+00.6)。患者纳入和排除没有充分的理由且报告不充分这一事实,使得对从原始论文获得的证据的解释产生了很大的不确定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3257/7894854/e48487cf7e50/pone.0245048.g001.jpg

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