| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Randomization of the study’s projected n of 456 was executed by computer in a location (Imperial College London) remote from the study site. Central allocation concealment was used. The randomization scheme was transmitted to the study institution’s central pharmacy, where it was translated to identical-appearing sequentially numbered drug-bottle sets." "the randomization scheme was seen only by the pharmacist who prepared the study bottles."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Triple-blinded. Study staff (physicians and nurses who enrolled participants, executed virologic sampling, and assessed and recorded participant’s clinical follow-up data) were unaware of study medication identity and did not see the contents of the study bottles. Study participants were unaware of the specific contents of their medication bottles.” "Successful blinding was suggested by a lack of association between group identity and study-medication guess (p = 0¢132). Study staff and analysts were asked to indicate whether they had learned of the study-bottle codes. All answers were negative."
Comment: Blinded study (patients, personnel and physicians). Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 456 patients randomized; 449 patients analyzed.
Seven patients not included in ITT analysis for primary negative conversion because no PCR result was available, which is unlikely to relate to outcome or true value. Quote: "Sensitivity analyses suggested that Q-PROTECT’s primary and secondary endpoint findings were not influenced by the relatively few missing data. Similar lack of influence from withdrawals was suggested by per-protocol analyses" Comment: Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and trial registry were available. The primary outcome (virologic cure/negative viral conversion) analyzed and presented as specified. Mortality and serious adverse events were not specified in the trial registry or protocol, however, we do not suspect and selective reporting of the results relating to those outcomes.
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Serious adverse events. |
| Overall risk of bias |
Low |