Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
|Bias||Author's judgement||Support for judgement|
|Quote:"randomly assigned (permuted blocks with concealed allocation) in a 1:1 ratio to hydroxychloroquine or azithromycin. Randomization was stratified by study site"
Comment: Allocation sequence probably random. Allocation sequence probably concealed
|Deviations from intervention||
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
In the hydroxychloroquine arm, 6 (14%) received nonrandomized azithromycin after study enrollment as original protocol allowed (generally as clinician-directed treatment for suspected pneumonia).
Administration of co-interventions of interest: antivirals, corticosteroids and biologics were reported. Remdesivir administration (given under an emergency use authorization) in the hydroxychloroquine vs azithromycin arms (8/42 vs. 1/43)
This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect
Data for the outcomes were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention.
Risk assessed to be some concerns for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
|Missing outcome data||
|Comment: 85 patients randomized; 84 patients analyzed for Mortality. 83 for Adverse events and Serious adverse events.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)
Mortality is an observer-reported outcome not involving judgement.
Risk assessed to be low for the outcome: Mortality (D28).
ADVERSE and SERIOUS ADVERSE EVENTS
The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events.
|Selection of the reported results||
|Comment: The protocol, statistical analysis plan (propective;submitted for publication 7th of April, 2020), registry were available (prospective; dates 1st of April 2020).
Mortality outcome was not specifically pre-specified in the, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned.
Result was not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality (D28).Adverse events. Serious adverse events.
|Overall risk of bias||