Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy and Study Eligibility
2.2. Study Selection
2.3. Data Extraction
2.4. Endpoint
2.5. Data Synthesis and Analysis
2.6. Assessment of the COVID-19 Rate in the Investigated Populations
2.7. Quality of Studies, Risk Bias, and Evidence Profile
2.8. Software and Statistical Significance
3. Results
3.1. Study Characteristics
3.2. Pairwise Meta-Analysis
3.3. Meta-Regression Analysis
3.4. SUCRA
3.5. Bias and Quality of Evidence
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study and Year with Reference | Logunov et al., 2021 [16] | Baden et al., 2020 [18] | Polack et al., 2020 [17] | Voysey et al., 2020 [15] |
---|---|---|---|---|
Trial number Identifier | NCT04530396 | NCT04470427 | NCT04368728 | ISRCTN89951424; NCT04324606, NCT04400838, NCT04444674 |
Vaccine developer | Gamaleya Research Institute | Moderna/National Institute of Allergy and Infectious Diseases’s Vaccine Research Center | BioNTech/Fosun Pharma/Pfizer | University of Oxford/AstraZeneca |
COVID-19 vaccine (dose and route of administration) | Sputnik V or Gam-COVID-Vac (1 × 1011 viral particles IM) | mRNA-1273 (100 μg IM) | BNT162b2 (30 µg IM) | AZD1222 or ChAdOx1 nCoV-19 (5 × 1010 viral particles IM) |
Study characteristics | Phase III, multicenter, randomized, double-blind, negative-controlled, parallel group | Phase III, multicenter, randomized, single-blind, stratified, parallel group | Phase III, multicenter, randomized, single-blind, negative-controlled, parallel group | Phase III, multicenter, randomized, single-blind, negative-controlled, parallel group |
Study duration with follow-up (weeks) | ~11 | ~17 | ~16 | ~21 |
Type of candidate vaccine | Recombinant adenovirus type 26 vector plus recombinant adenovirus type 5 vector carrying the gene for SARS-CoV-2 full-length spike glycoprotein | LNP-encapsulated nucleoside-modified mRNA vaccine encoding SARS-CoV-2 prefusion-stabilized full-length spike glycoprotein trimer | Three LNP-encapsulated nucleoside-modified mRNA vaccine encoding trimerized SARS-CoV-2 RBD antigen of spike glycoprotein | Replication-defective chimpanzee adenovirus-vectored vaccine expressing full-length SARS-CoV-2 spike glycoprotein gene |
Number of scheduled doses (timing of inoculations) | Prime and boost inoculation (0, 21 days) | Prime and boost inoculation (0, 28 days) | Prime and boost inoculation (1, 22 days) | Prime and boost inoculation (0, 28–90 days) |
Number of participants | 15,366 | 28,207 | 37,086 | 8895 |
Vaccine recipients characteristics | Healthy adults with negative PCR and IgG and IgM to SARS-CoV-2, with no history of COVID-19 or contact with COVID-19 patients in the preceding 2 weeks before enrolment | Healthy adults or adults with pre-existing stable medical conditions, with no history of SARS-CoV-2 infection | Healthy adults or adults with pre-existing stable medical conditions, with no history of COVID-19, and not taking medications intended to prevent COVID-19 | Healthy adults at high risk of exposure to SARS-CoV-2 |
Age (mean and range) | 45.3 (18.0–87.0) | 51.4 (18.0–95.0) | 52.8 (16.0–91.0) | ≥18.0 |
Male (%) | 61.3 | 52.7 | 50.6 | 41.1 |
Rate of COVID-19 cases (number of cases/100,000 inhabitants/14 days) | 343 | 190 | 320 | 279 |
Jadad score | 5 | 3 | 3 | 3 |
Co-variate | Regression Coefficient, Mean and 95%CI | p Value | Modifying Factor |
---|---|---|---|
Vaccine type | |||
Overall | −1.227 (−2.355–−0.099) | 0.033 | Yes |
Sensitivity analysis by excluding AZD1222 | −0.430 (−1.149–0.289) | 0.241 | No |
Rate of COVID-19 cases | 0.001 (−0.013–0.015) | 0.933 | No |
Age | |||
Overall | 0.014 (−0.008–0.036) | 0.215 | No |
mRNA-based vaccines | 0.023 (−0.003–0.049) | 0.081 | No, but detected a trend toward significance |
Adenovirus-based vaccines | −0.005 (−0.046–0.036) | 0.807 | No |
Sex | −0.539 (−1.261–0.183) | 0.144 | No |
COVID-19 Vaccine | SUCRA (%) |
---|---|
BNT162b2 | 0.75 |
mRNA-1273 | 0.71 |
Sputnik V | 0.62 |
AZD1222 | 0.33 |
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Calzetta, L.; Ritondo, B.L.; Coppola, A.; Matera, M.G.; Di Daniele, N.; Rogliani, P. Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials. Vaccines 2021, 9, 341. https://doi.org/10.3390/vaccines9040341
Calzetta L, Ritondo BL, Coppola A, Matera MG, Di Daniele N, Rogliani P. Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials. Vaccines. 2021; 9(4):341. https://doi.org/10.3390/vaccines9040341
Chicago/Turabian StyleCalzetta, Luigino, Beatrice Ludovica Ritondo, Angelo Coppola, Maria Gabriella Matera, Nicola Di Daniele, and Paola Rogliani. 2021. "Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials" Vaccines 9, no. 4: 341. https://doi.org/10.3390/vaccines9040341
APA StyleCalzetta, L., Ritondo, B. L., Coppola, A., Matera, M. G., Di Daniele, N., & Rogliani, P. (2021). Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials. Vaccines, 9(4), 341. https://doi.org/10.3390/vaccines9040341