Professor Cao Bin: In the treatment of COVID-19, we should believe in evidence and not superstitiously believe in authority

Author: Shang Yihan, Beijing University of Traditional Chinese Medicine, National Respiratory Medicine Center, China-Japan Friendship Hospital, Cao Bin

National Center for Respiratory Medicine China-Japan Friendship Hospital Cao Bin

The COVID-19 pandemic continues, and the mutated virus strain has brought a more severe test to the prevention and control of the global epidemic. This requires clinical medical practitioners to guide clinical practice based on evidence-based medical evidence and respond objectively and normatively to the COVID-19 pandemic.

In the early stages of the outbreak, only some observational studies and small sample clinical trials suggested that hydroxychloroquine could bring clinical benefits, and this drug, which has not been rigorously evaluated for RCT, is used by a wide range of hyperattracties worldwide. Subsequent RCT analyses have demonstrated that hydroxychloroquine treatment has not yielded benefits and may even increase the incidence of adverse events in terms of important clinical outcomes such as reducing case fatality, accelerating clinical recovery, and shortening hospital stay. As evidence has accumulated, subsequent updated national guidelines have deprecated the use of hydroxychloroquine.

The widespread abuse of hydroxychloroquine in the early stages of the outbreak is an important implication for our rational response to a new acute infectious disease: rigorously designed RCTs to assess the efficacy and safety of drug candidates are critical to forming clinical decisions. The RECOVERY trial and the SOLIDIDARITY trial assessed the efficacy and safety of multiple drugs through a large sample RCT system, providing conclusive evidence for clinical decision-making. The success of large RCTs such as the RECOVERY trial and the SOLIDIDARITY trial provides a valuable model for future pandemic research. It is important to coordinate research resources in endemic areas and expand the RCT sample size. Since small sample RCTs do not yield conclusive evidence, investigators should be encouraged to increase or participate in large RCTs in multicenter collaboration.

IL-6R inhibitors were used as candidates for the treatment of COVID-19 in the early stages of the pandemic, and several RCT studies have been conducted around the world, but the conclusions of the different studies are not completely consistent. Only one of the five RCTs published in 2020 suggested clinical benefit, and meta-analyses of these five trials suggested that tocilizumab treatment did not reduce case fatality in patients, so guidelines in the early stages of the outbreak did not recommend the use of tocilizumab. The 2021 REMAP-CAP trial and the REUNITY trial showed that receiving tocilizumab therapy reduced mortality and risk of invasive mechanical ventilation. Updated meta-analyses suggest that tocilizumab can reduce case fatality in patients with COVID-19. Current guidelines have recommended that clinicians consider using tocilizumab in addition to glucocorticoid therapy in some severely ill populations. The example of tocilizumab illustrates the need for rapid clinical application of high-quality research evidence and dynamic update of guideline recommendations based on emerging evidence. At the same time, when reading the guidelines, it is necessary to pay attention to the applicable population of the evidence, the limitations of the evidence and the differences in the methodology of different guideline formulations.

"Do no harm" is a basic principle of clinical practice. Clinicians should use medications based on evidence and avoid blind hyper-indications. Especially for emerging infectious diseases, drugs that appear useful are likely to prove ineffective or even harmful in the future. Clinicians should respect the evidence, interpret the evidence in combination with clinical practice, and not superstitiously believe in any form of "authority".

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