Covid-19 Living Data

Trial NCT05142553
Publication Corominas J, Lancet Reg Health Eur, 2023
Primary outcome on the report: 1) Humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost
2) Safety and tolerability of PHH-1V as a boost

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: "Subjects were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine (third immunization) either with the HIPRA PHH-1V vaccine (PHH-1V group) or with the Pfizer/BioNTech BNT162b2 vaccine (BNT162b2 group). Subjects were allocated to treatment using an Interactive Response Technology (IRT)" Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention	Some concerns	Quote: "double-blind" trial. Comment: Blinded study (participants and personnel/carers). MORTALITY, LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS Safety analysis on those who received at least one dose of the intervention 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. Local adverse events. Systemic adverse events. adverse events. Serious Adverse events. NEUTRALIZING SEROCONVERSION RATE. NEUTRALIZING ANTIBODY GMTs, NEUTRALIZING ANTIBODY GMTs OMICRON Per-protocol analysis was performed on the outcome. Reasons for exclusion: 18 vs 12 protocol deviations. 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 relatively small number. Risk assessed to be some concerns for the outcome: Neutralizing seroconversion rate. Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. NEUTRALIZING SEROCONVERSION RATE (>90D), NEUTRALIZING ANTIBODY GMTs (>90D), NEUTRALIZING ANTIBODY GMTs OMICRON (>90D) Per-protocol analysis was performed on the outcome. Quote:"...including all subjects in the mITT without COVID-19 infections recorded via adverse event reporting prior to their Day 98 visit date" There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to balance between arms. Risk assessed to be some concerns for the outcome: Neutralizing seroconversion rate (>90 days). Neutralizing antibody GMT (>90 days). Neutralizing antibody GMT Omicron (>90 days).
Missing outcome data	Low	Comment: 782 participants randomized; 765 (98%) participants analyzed for safety and mortality; 749 analyzed for Neutralizing antibody GMTs and Neutralizing antibody GMTs Omicron. 120 participants analyzed for Neutralizing antibody GMTs (>90 days) and Neutralizing antibody GMTs Omicron (>90 days). MORTALITY, LOCAL, SYSTEMIC, ADVERSE EVENTS and SERIOUS ADVERSE EVENTS Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious Adverse events. NEUTRALIZING SEROCONVERSION RATE, NEUTRALIZING ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT OMICRON Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: 30 protocol violations were accounted for in domain 2. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Neutralizing seroconversion rate. Neutralizing antibody GMT Omicron. NEUTRALIZING SEROCONVERSION RATE (>90D), NEUTRALIZING ANTIBODY GMT (>90 days), NEUTRALIZING ANTIBODY GMT OMICRON (>90 days) Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: No reasons reported other than "COVID-19 infections recorded via adverse event reporting prior to their Day 98 visit date" Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome de to balance between arms. Risk assessed to be some concerns for the outcomes:Neutralizing seroconversion rate (>90 days). Neutralizing antibody GMT (>90 days). Neutralizing antibody GMT Omicron (>90 days).
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. Neutralizing seroconversion rate. Neutralizing seroconversion rate (>90 days) Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90 days). Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results	Low	Comment: The protocol, statistical analysis plan, and registry were available (dated December 2, 2021, but submitted November 17). Outcome 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. Neutralizing seroconversion rate. Neutralizing seroconversion rate (>90 days) Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90 days). Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias	Some concerns