Addis Antonio, Amato Laura, Cruciani Fabio, Saulle Rosella, De Crescenzo Franco, Mitrova Zuzana, Vecchi Simona, Perrone Francesco, Davoli Marina
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.
Front Pharmacol. 2021 Oct 18;12:749514. doi: 10.3389/fphar.2021.749514. eCollection 2021.
Standard of Care (SoC) has been used with different significance across Randomized Clinical Trials (RCTs) on the treatment of Covid-19. In the context of a living systematic review on pharmacological interventions for COVID-19, we assessed the characteristics of the SoC adopted in the published RCTs. We performed a systematic review searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to April 10, 2021. We included all RCTs comparing any pharmacological intervention for Covid-19 against any drugs, placebo, or SoC. All trials selected have been classified as studies with SoC including treatments under investigation for COVID-19 (SoC+); studies with SoC without specifications regarding the potential therapies allowed (SoC-); studies including as control groups Placebo (P) or active controls (A+). We included in our analysis 144 RCTs, comprising 78,319 patients. Most of these trials included SoC (108; 75.0%); some in all arms of the study (69.7%) or just as independent comparators (30.3%). Treatments under investigation for COVID-19 in other trials were included in the SoC (SoC+) in 67 cases (62.0%), Thirty-one different therapeutic agents (alone or in combination) were counted within the studies with SoC+: mostly hydroxychloroquine or chloroquine (28), lopinavir/ritonavir (20) or azithromycin (16). No specification was given regarding treatment allowed in the control groups (SoC-) in 41 studies (38.0%). Our analysis shows that the findings emerging from several clinical trials regarding the efficacy and safety of pharmacological intervention for COVID-19 might be jeopardized by the quality of control arms.
在关于新冠肺炎治疗的随机临床试验（RCT）中，护理标准（SoC）有着不同的含义。在一项关于新冠肺炎药物干预的实时系统评价中，我们评估了已发表的随机对照试验中采用的护理标准的特征。我们进行了一项系统评价，检索了截至2021年4月10日的Medline、Pubmed、Embase、Cochrane新冠肺炎注册库、国际试验注册库、medRxiv、bioRxiv和arXiv。我们纳入了所有比较任何新冠肺炎药物干预与任何药物、安慰剂或护理标准的随机对照试验。所有选定的试验都被归类为有护理标准的研究，包括正在研究的新冠肺炎治疗（SoC+）；有护理标准但未明确允许的潜在治疗方法的研究（SoC-）；包括安慰剂（P）或活性对照（A+）作为对照组的研究。我们的分析纳入了144项随机对照试验，涉及78319名患者。这些试验中的大多数都包括护理标准（108项；75.0%）；有些在研究的所有组中（69.7%），或者只是作为独立的对照（30.3%）。在其他试验中，正在研究的新冠肺炎治疗在67例（62.0%）中被纳入护理标准（SoC+）。在有SoC+的研究中，共统计了31种不同的治疗药物（单独或联合使用）：主要是羟氯喹或氯喹（28种）、洛匹那韦/利托那韦（20种）或阿奇霉素（16种）。41项研究（38.0%）中未明确说明对照组允许的治疗方法（SoC-）。我们的分析表明，一些关于新冠肺炎药物干预疗效和安全性的临床试验结果可能会受到对照组质量的影响。
