Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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Background Ensuring that countries have adequate research capacities is essential for an effective and efficient response to infectious disease outbreaks. The need for ethical principles and values embodied in international research ethics guidelines to be upheld during public health emergencies is widely recognized. Public health officials, researchers and other concerned stakeholders also have to carefully balance time and resources allocated to immediate treatment and control activities, with an approach that integrates research as part of the outbreak response. Under such circumstances, research “ethics preparedness” constitutes an important foundation for an effective response to infectious disease outbreaks and other health emergencies. Main text A two-day workshop was convened in March 2018 by the World Health Organisation Global Health Ethics Team and the African coaLition for Epidemic Research, Response and Training, with representatives of National Ethics Committees, to identify practical processes and procedures related to ethics review preparedness. The workshop considered five areas where work might be undertaken to facilitate rapid and sound ethics review: preparing national ethics committees for outbreak response; pre-review of protocols; multi-country review; coordination between national ethics committees and other key stakeholders; data and benefit sharing; and export of samples to third countries. In this paper, we present the recommendations that resulted from the workshop. In particular, the participants recommended that Ethics Committees would develop a formal national standard operating procedure for emergency response ethical review; that there is a need to clarify the terminology and expectations of pre-review of generic protocols and agree upon specific terminology; that there is a need to explore mechanisms for multi-country emergency ethical consultation, and to establish procedures for communication between national ethics committees and other oversight bodies and public health authorities. In addition, it was suggested that ethics committees should request from researchers, at a minimum, a preliminary data sharing and sample sharing plan that outlines the benefit to the population from which data and samples are to be drawn. This should be followed in due time by a full plan. Conclusion It is hoped that the national ethics committees, supported by the WHO, relevant collaborative research consortia and external funding agencies, will work towards bringing these recommendations into practice, for supporting the conduct of effective research during outbreaks.

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