Covid-19 Living Data

Trial IRCT20150303021315N23 ; NCT04944368
Publication Tabarsi P, CMI, 2022
Primary outcome on the report: 1) The primary safety outcomes were the incidence of local and systemic solicited adverse events for 7 days after each dose and the incidence of unsolicited adverse events up to 28 days after the second dose. 2) The primary immunogenicity outcomes were seroconversion rate against S1 protein and the geometric mean concentration (GMC) of S1 IgG in the two groups on days 21 and 35.

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
Randomization	Low	Quote: "Eligible participants were randomly assigned to each group using a stratified randomization with 3:1 allocation ratio by R-CRAN-version 4.0.1... Once the randomizationwas made, each patient was given an identification code throughout the study. Consecutive allocation of the randomization code to the participants was concealed by use of the unblinded pharmacists who prepared the investigational product in a secure location that was not accessible or visible to other study staff. The vaccine preparer was unmasked but played no role in the data assessment, and the vaccine administrators, participants, and outcome assessors were blinded." Comment: Allocation sequence random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention	Some concerns	Quote: “Consecutive allocation of the randomization code to the par- ticipants was concealed by use of the unblinded pharmacists who prepared the investigational product in a secure location that was not accessible or visible to other study staff. The vaccine preparer was unmasked but played no role in the data assessment, and the vaccine administrators, participants, and outcome assessors were blinded.” "double-blind phase 2 trial" Comment: Blinded study (participants and personnel/carers). MORTALITY, CELLULAR RESPONSE ITT analysis. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Risk assessed to be low for the outcomes: Mortality, Cellular response. LOCAL and SYSTEMIC ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Per-protocol analysis was performed on the outcomes. Reasons for exclusion: 1 participant received the wrong intervention and was analyzed according to intervention received. As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to the small number. Risk assessed to be some concerns for the outcomes: Local adverse events and Systemic adverse events. Serious adverse events.
Missing outcome data	Low	Comment: 400 participants randomized; 75 participants analyzed for Cellular response; at least 394 analyzed for the other review outcomes. MORTALITY, CONFIRMED SYMPTOMATIC COVID, LOCAL and SYSTEMIC ADVERSE EVENTS, and SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality, Confirmed symptomatic COVID, Local adverse events, Systemic adverse events, and Serious adverse events. CELLULAR RESPONSE Data not available for nearly all participants randomized. No evidence that the result is not biased. Reason: a random sample of only 75 participants were tested for this outcome. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcome: Cellular response.
Measurement of the outcome	Low	Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality. Cellular response. Local adverse events. Systemic adverse events. Serious adverse events.
Selection of the reported results	Low	Comment: The prospective registry was available (Date: May 5th, 2022). Outcomes pre-specified. 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. Cellular response. Local adverse events. Systemic adverse events. Serious adverse events.
Overall risk of bias	Some concerns