A Quantitative Benefit–Risk Analysis of ChAdOx1 nCoV-19 Vaccine among People under 60 in Italy

  1. Raffaele Palladino
  2. Daniele Ceriotti
  3. Damiano De Ambrosi
  4. Marta De Vito
  5. Marco Farsoni
  6. Giuseppina Seminara
  7. Francesco Barone-Adesi

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Abstract

The Oxford-AstraZeneca ChAdOx1 nCoV-19 is a vaccine against the COVID-19 infection that was granted a conditional marketing authorization by the European Commission in January 2021. However, following a report from the Pharmacovigilance Risk Assessment Committee (PRAC) of European Medicines Agency, which reported an association with thrombo-embolic events (TEE), in particular disseminated intravascular coagulation (DIC) and cerebral venous sinus thrombosis (CVST), many European countries either limited it to individuals older than 55–60 years or suspended its use. We used publicly available data to carry out a quantitative benefit–risk analysis of the vaccine among people under 60 in Italy. Specifically, we used data from PRAC, Eudravigilance and ECDC to estimate the excess number of deaths for TEE, DIC and CVST expected in vaccine users, stratified by age groups. We then used data from the National Institute of Health to calculate age-specific COVID-19 mortality rates in Italy. Preventable deaths were calculated assuming a 72% vaccine efficacy over an eight-month period. Finally, the benefit–risk ratio of ChAdOx1 nCoV-19 vaccination was calculated as the ratio of preventable COVID-19 deaths to vaccine-related deaths, using Monte-Carlo simulations. We found that among subjects aged 20–29 years the benefit–risk (B-R) ratio was not clearly favorable (0.70; 95% Uncertainty Interval (UI): 0.27–2.11). However, in the other age groups the benefits of vaccination largely exceeded the risks (for age 30–49, B-R ratio: 22.9: 95%UI: 10.1–186.4). For age 50–59, B-R ratio: 1577.1: 95%UI: 1176.9–2121.5). Although many countries have limited the use of the ChAdOx1 nCoV-19 vaccine, the benefits of using this vaccine clearly outweigh the risks in people older than 30 years. Study limitations included risk of underreporting and that we did not provide age-specific estimates. The use of this vaccine should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.

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  1. Version published to 10.3390/vaccines9060618
  2. ScreenIT

    SciScore for 10.1101/2021.05.07.21256826: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: No ethics committee approval was necessary.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using Stata version 15 (StataCorp, College Station, TX).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our work has some limitations, the main one being represented by the possible under-reporting of the data reported in the Eudravigilance database. As the adverse effects are not always reported, the real cases of thrombotic events may be higher than those detected. As shown in Table 3, however, even in the presence of substantial under-reporting, the results suggest a clear benefit in everybody aged at least 30 years. Another important limitation is related to the fact that we did not produce gender-specific estimates. Future research should evaluate whether this vaccine is associated with larger TEE risk among young women, also considering that some of them take estrogen-progestin contraceptives or hormone replacement therapy. COVID-19 is having a dramatic impact on the Italian and other European Health Systems. Therefore, the use of ChAdOx1 nCoV-19 vaccine, extending its recommendation to younger population as well, should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.05.07.21256826v1 on medRxiv