For each eligible trial, pairs of reviewers, following training and calibration exercises, extracted data independently using a standardised, pilot tested data extraction form. Reviewers collected information on trial characteristics (trial registration, publication status, study status, design), patient characteristics (country, age, sex, smoking habits, comorbidities, setting and type of care, and severity of covid-19 symptoms for studies of treatment), and outcomes of interest (means or medians and measures of variability for continuous outcomes and the number of participants analysed and the number of participants who experienced an event for dichotomous outcomes). Reviewers resolved discrepancies by discussion and, when necessary, with adjudication by a third party. We updated the data collected from included preprints as soon as the peer review publication became available.
Outcomes of interest were selected based on importance to patients18 (link) and were informed by clinical expertise in the systematic review team and in the linked guideline panel responsible for the WHO-BMJ Rapid Recommendations.19 (link)
7 (link)
8 (link) The panel includes unconflicted clinical and methodology experts, recruited to ensure global representation, and patient partners. All panel members rated outcomes from 1 to 9 based on importance to individual patients (9 being most important), and we included any outcome rated 7 or higher by any panel member. Selected outcomes included mortality (closest to 90 days), mechanical ventilation (total number of patients, over 90 days), adverse events leading to discontinuation (within 28 days), admission to hospital, length of hospital stay, duration of mechanical ventilation, and time to symptom resolution or clinical improvement. In contrast to previous iterations, for this iteration, we did not include several outcomes which the GDG did not think were critical to decision making: viral clearance (closest to 7 days, 3 days either way), time to viral clearance, intensive care unit (ICU) length of stay, and days free from mechanical ventilation (within 28 days).
Mechanical ventilation includes both invasive and non-invasive mechanical ventilation. We used a hierarchy for the outcome mechanical ventilation in which we preferentially used the total number of patients who received mechanical ventilation over the study. We used the number of patients ventilated at the time point that the largest number of the patients were ventilated, if the trial reported the number of patients ventilated at specific timepoints. We used author definitions for mechanical ventilation; when separate, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) were considered non-invasive mechanical ventilation.
Outcomes of interest were selected based on importance to patients18 (link) and were informed by clinical expertise in the systematic review team and in the linked guideline panel responsible for the WHO-BMJ Rapid Recommendations.19 (link)
7 (link)
8 (link) The panel includes unconflicted clinical and methodology experts, recruited to ensure global representation, and patient partners. All panel members rated outcomes from 1 to 9 based on importance to individual patients (9 being most important), and we included any outcome rated 7 or higher by any panel member. Selected outcomes included mortality (closest to 90 days), mechanical ventilation (total number of patients, over 90 days), adverse events leading to discontinuation (within 28 days), admission to hospital, length of hospital stay, duration of mechanical ventilation, and time to symptom resolution or clinical improvement. In contrast to previous iterations, for this iteration, we did not include several outcomes which the GDG did not think were critical to decision making: viral clearance (closest to 7 days, 3 days either way), time to viral clearance, intensive care unit (ICU) length of stay, and days free from mechanical ventilation (within 28 days).
Mechanical ventilation includes both invasive and non-invasive mechanical ventilation. We used a hierarchy for the outcome mechanical ventilation in which we preferentially used the total number of patients who received mechanical ventilation over the study. We used the number of patients ventilated at the time point that the largest number of the patients were ventilated, if the trial reported the number of patients ventilated at specific timepoints. We used author definitions for mechanical ventilation; when separate, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) were considered non-invasive mechanical ventilation.
