Tensions between research and public health: modelling the risks and benefits of SARS-CoV-2 vaccine field trials versus human infection challenge studies.

  1. George S Heriot
  2. Euzebiusz Jamrozik
  3. Michael J Selgelid

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Abstract

Background: Human infection challenge studies (HICS) with SARS-CoV-2 are under consideration as a way of accelerating vaccine development. We evaluate potential vaccine research strategies under a range of epidemic conditions determined, in part, by the intensity of public health interventions. Methods: We constructed a compartmental epidemiological model incorporating public health interventions, vaccine efficacy trials and a post-trial population vaccination campaign. The model was used to estimate the duration and benefits of large-scale field trials in comparison with HICS accompanied by an expanded safety trial, and to assess the marginal risk faced by HICS participants. Results: Field trials may demonstrate vaccine efficacy more rapidly than a HICS strategy under epidemic conditions consistent with moderate mitigation policies. A HICS strategy is the only feasible option for testing vaccine efficacy under epidemic suppression, and maximises the benefits of post-trial vaccination. Less successful or absent mitigation results in minimal or no benefit from post-trial vaccination, irrespective of trial design. Conclusions: SARS-CoV-2 HICS are the optimal method of vaccine testing for populations maintained under epidemic suppression, where vaccination offers the greatest benefits to the local population.

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    SciScore for 10.1101/2020.05.18.20106187: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    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:
    Major practical caveats of field trials under mitigation policies include (i) reliance on a sophisticated public health response able to calibrate transmission control measures to within the required range for Reff and (ii) progressive challenges of identifying (with imperfectly sensitive serological assays) and recruiting large numbers of susceptible (never-infected) participants as a larger proportion of the population becomes infected or immune.[27] Benefits and risks of HICS in the context of epidemic suppression: A strategy of HICS followed by post-trial vaccination is superior to field trials in our model where Reff is less than 1.14 (at 90% vaccine efficacy) to 1.3 (50% vaccine efficacy), both in terms of the reduction in population mortality from vaccination and the duration of transmission control measures (Figure 1). In this setting a HICS strategy has two additional advantages not considered in our simplified vaccine development timeline. First, HICS permit comparison of multiple candidate vaccines in the same population, free from phenomena that might compromise the interpretation of field trials including the interactions of indirect effects of multiple vaccines and the inclusion of non-comparable study populations in multi-centre trials.[12] Second, a HICS strategy permits testing vaccine efficacy despite very low rates of population transmission, and if suppression policies are maintained, additional delays (e.g., in vaccine development or population vaccinatio...

    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.
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  2. Version published to 10.1101/2020.05.18.20106187 on medRxiv