| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: The permuted block (four patients per block) randomization sequence, including stratification, was prepared by a statistician not involved in the trial, using SAS software, version 9.4 (SAS Institute). To minimize allocation bias, we performed allocation concealment with an interactive Web-based response system until randomization was finished on the system through a computer or phone. Comment: The allocation sequence was concealed |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study.
A small number of participants crossed over (3 out of 100; 2 were assigned to the lopinavir-ritonavir arm but did not receive the intervention, 1 was assigned to the standard care arm but received lopinavir-ritonavir). Deviations are too small to affect the outcome No information on administration of co-intervention of interest: biologics. Antivirals, and corticosteroids were reported. Efficacy outcome data were analyzed by using modified intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 199 randomized, 199 analyzed for all outcomes except viral negative conversion (n=130 analyzed, excluding participants without detectable viral RNA at baseline; excluding ineligible participants post-randomization is acceptable). Risk assessed to be "low" for the outcomes: Mortality. Time to death. Adverse events. Serious adverse events. WHO score 6 or above . WHO score 7 or above. Time to Clinical Improvement. Clinical improvement incidence. Viral negative conversion incidence. |
| Measurement of the outcome |
Some concerns |
Comment: The outcomes that concern clinical improvement/progression are observer-measured outcomes that involve clinical decision-making, and the assessment could theoretically be influence by knowledge of the intervention assignment, though we do not consider this likely in the context of the pandemic. The outcomes in question are not statistically significant. We consider that the outcome WHO clinical progression scale score 7 or above cannot be influenced by knowledge of the intervention assignment. Some adverse-events were patient-reported or involved assessor judgment. The remaining outcomes are observer-measured and do not involve clinical decision-making. Risk assessed to be "low" for the outcomes: Mortality. Time to death. Viral Negative Conversion incidence. WHO score 7 or above. Risk assessed to be "some concerns" for the outcomes: WHO score 6 or above. Time to Clinical Improvement. Clinical improvement incidence. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol was available (in Chinese with the final part presented in English regarding outcomes; the part that was in Chinese was examined by a native speaker). The statistical analysis plan was available.
Outcomes were pre-specified in the protocol and SAP as reported in the paper. Results were 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. Time to death. Incidence of viral negative conversion. Time to Clinical Improvement. Clinical improvement incidence. WHO score 6 or above. WHO score 7 or above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |