Taking a stand against the politicization of medical research: how 'swinging the pendulum' poses a hazard to clinical trials, study participants, and the progress of science.
Taking a stand against the politicization of medical research: how 'swinging the pendulum' poses a hazard to clinical trials, study participants, and the progress of science.
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反对医学研究的政治化：“摇摆”如何对临床试验、研究参与者和科学进步构成危害。
DOI：
10.1080/1744666x.2020.1860758
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发表时间：
2021
影响因子：
4.4
通讯作者：
Barnabas,RuanneV
中科院分区：
文献类型：
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作者：
Bershteyn,Anna;Schwartz,MarkD;Thorpe,LornaE;Paasche-Orlow,MichaelK;Kissinger,Patricia;StankiewiczKarita,HelenC;Laufer,MiriamK;Hoffman,RisaM;Landovitz,RaphaelJ;Paolino,Kristopher;Barnabas,RuanneV
在SARS-CoV-2大流行的早期，几十年来一直用于治疗疟疾和自身免疫性疾病的药物羟氯喹成为家喻户晓的名字。萨图伊和他的同事描述了公众对羟氯喹的极端看法，从早期的热情到广泛的怀疑。在这种观点的“钟摆摆动”过程中，研究人员努力积累越来越明确的证据，证明羟氯喹对不同潜在适应症的安全性和有效性，如暴露前预防（PrEP）、暴露后预防（PEP）、早期和轻度疾病治疗以及中度或重度疾病治疗。公众话语的“钟摆摆动”对进行临床试验和确保参与者健康的能力产生了深远的影响。我们在最近完成的羟氯喹PEP研究中亲身体验了这些挑战，该研究在美国各地招募了参与者。重要的是要在Sattui等人的综述中补充“钟摆摆动”对研究进展和试验参与者福祉的影响，因为这对疫苗和治疗试验具有深远的影响。2020年2月，中国武汉的科学家报告说，氯喹可以抑制Vero细胞中的SARS-CoV-2复制。2020年3月中旬，羟基氯喹[4]发表了类似的研究结果。在人类中，早期的小型研究提出了这些药物可能减少病毒脱落并改善结果的可能性。面对紧急情况，但仅凭这一不足的证据，医学界转向使用羟氯喹，因为羟氯喹的广泛可用性和数十年来安全用于治疗其他疾病的历史。在迫切需要明确证据的推动下，像我们这样的试验迅速开展，最初的入学率很高。2020年3月，当美国总统唐纳德·特朗普和特斯拉首席执行官埃隆·马斯克等公众人物开始推广这种药物时，羟氯喹的处方急剧飙升，以至于几个州禁止了标签外处方，以防止药物短缺。对于一些研究参与者来说，临床试验提供了一种获得突然稀缺药物的途径，同时也为科学做出了贡献。今年4月，就在随机试验正在进行之际，两项发现引发了毫无根据的恐惧。巴西的一项研究报告，接受高剂量氯喹[6]治疗的老年研究参与者中有几例心脏死亡。媒体广泛报道了这些死亡事件，但在信息传递中忽略了这样一个事实，即大多数研究使用的是更安全的羟氯喹，剂量要低得多，并且有长达60年的安全记录。不久之后，退伍军人管理局的一项观察性研究报告称，服用羟氯喹的重症患者死亡率更高，但该研究不是随机的，因此有可能接受治疗的患者比未接受治疗的患者病情更重。事实上，2020年7月的一项观察性研究发现了相反的趋势——接受羟氯喹治疗的患者死亡率较低。科学界认识到这些局限性，并继续支持研究。然而，这些不确定的证据被媒体描绘成支持使用羟氯喹的公众人物是错误的证据。我们的研究经历了招募人数急剧下降的过程，一些参与者斥责我们使用了“特朗普的药”。然后，在2020年5月18日，外科手术研究发表了：发表在《柳叶刀》杂志上的一项大型回顾性分析报告称，全球羟氯喹治疗的COVID-19患者死亡率更高。一些科学家立即发现了论文中可疑的不一致之处，并写了一篇公开的……
Early in the SARS-CoV-2 pandemic, the drug hydroxychloroquine, which had been used for decades to treat malaria and autoimmune disorders, became a household name. Sattui and colleagues [1] describe the extremes of public discourse about hydroxychloroquine, from early enthusiasm to widespread skepticism. Throughout this ‘pendulum swing’of opinion, researchers worked to accrue increasingly definitive evidence about the safety and efficacy of hydroxychloroquine for different potential indications, such as pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), early and mild disease treatment, and moderate or severe disease treatment. The ‘pendulum swing’of public discourse had profound effects on the ability to conduct clinical trials and ensure well-being of participants. We experienced these challenges firsthand in our recently completed hydroxychloroquine PEP study, which enrolled participants across the United States [2]. It is important to add to Sattui et al.’s review the impact of the ‘pendulum swing’on the progress of research and well-being of trial participants because of the profound implications for vaccine and treatment trials. In February 2020, scientists in Wuhan, China reported that SARS-CoV-2 replication in Vero cells was inhibited by chloroquine [3]. Similar findings were published in mid-March, 2020 with hydroxychloroquine [4]. In humans, early small studies raised the possibility that these drugs might reduce viral shedding and improve outcomes [5]. Facing an emergency, but armed only with this scant evidence, medical communities turned to hydroxychloroquine because of its wide availability and decades-long history of safe use to treat other conditions. Fueled by the urgent need for definitive evidence, trials like ours launched rapidly, initially with high rates of enrollment. When public figures like US President Donald Trump and Tesla CEO Elon Musk began promoting the drug in March 2020, hydroxychloroquine prescriptions spiked so sharply that several States banned off-label prescribing to prevent drug shortages. For some study participants, clinical trials provided a way to access a suddenly scarce drug while also contributing to science. In April, just as randomized trials were getting underway, two findings stoked unwarranted fear. A study from Brazil reported several cardiac deaths in older study participants receiving high-dose chloroquine [6]. The deaths were widely covered in the media, but lost in the messaging was the fact that most studies used the safer hydroxychloroquine at a much lower dose with a six-decade-long safety record. Soon afterward, an observational study from the Veterans Administration reported that severely ill patients given hydroxychloroquine had higher mortality rates [7], but the study was not randomized, leaving open the possibility that treated patients were sicker than untreated patients. Indeed, a July 2020 observational study [8] found the opposite trend–lower mortality among those receiving hydroxychloroquine. The scientific community recognized these limitations and remained supportive of research. However, the inconclusive evidence was portrayed in the media as proof that the public figures supporting the use of hydroxychloroquine were wrong. Our study experienced a sharp drop in recruitment, with some participants berating us for using ‘Trump’s drug.’Then, on May 18, 2020, came the Surgisphere study: a large retrospective analysis published in The Lancet [9] which reported higher mortality rates in hydroxychloroquine-treated COVID-19 patients worldwide. While some scientists immediately identified suspicious inconsistencies in the publication, writing an open …