Does This COVID-19 Vaccine Work?

Challenges assessing the clinical efficacy of SARS-CoV-2 vaccines
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(Coronavirus Today)

Assessing the efficacy of any vaccine is complex for many diseases, but particularly so in the case of SARS-CoV-2, where the fundamental understanding of the pathogen is evolving, said researchers in a review published by The Lancet.

With multiple vaccines in early-phase studies and some vaccine candidates in phase 3 studies assessing efficacy, ‘it is probable that there will not be a single vaccine winner,’ stated this article published on October 27, 2020.

A candidate vaccine against SARS-CoV-2 might ‘act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials.’

This conclusion is based on diverse platforms and technologies that can offer different strengths and be relevant in distinct epidemiological contexts. Additionally, there will probably be insufficient supply, at least initially, of a single vaccine.

In their target product profile for COVID-19 vaccines, the World Health Organization suggested that a “clear demonstration of efficacy ideally with ∼50% point estimate” should be a minimum criterion for any acceptable COVID-19 vaccine, and that efficacy can be assessed against “disease, severe disease, and/or shedding/transmission” endpoints.

This definition is necessarily non-specific and reflects the complexities of assessing the clinical efficacy of candidate vaccines in the context of a novel pathogen. 

Indeed, a COVID-19 vaccine capable of reducing any of these elements might contribute to disease control where there are no efficacious prophylactic medications and few treatments.

The US Food and Drug Administration suggested that laboratory-confirmed COVID-19 or SARS-CoV-2 infection are appropriate primary endpoints for vaccine efficacy studies, with an endpoint estimate of at least 50% for placebo-controlled efficacy trials.

However, the ‘collaboration and standardized approaches for assessing different efficacy endpoints will be important to allow meaningful comparison and ensure that the most effective candidates are deployed.’ 

Following deployment, well-supported pharmacovigilance studies should be established to ensure the ongoing evaluation of vaccine safety.

In the absence of a surrogate of protection, the Controlled Human Infection Model (CHIM) trials might provide the only means of rapidly assessing vaccine efficacy; however, the relationship between efficacy data from CHIM studies in young individuals and population-level protection is unclear. 

CHIM studies might help to identify a surrogate of protection. It is probable that any evidence for efficacy against severe disease and mortality in populations that are at risk will only be garnered post-licensure via large epidemiological studies.

Finally, ‘the development of SARS-CoV-2 vaccines is under great political and media scrutiny. In keeping with the development of any novel medical intervention, but particularly so in this context, it is imperative that efficacy outcomes for a SARS-CoV-2 vaccine are critically appraised with scientific rigor to understand their generalisability and clinical significance,’ concluded this review.

This work was supported by the National Institute for Health Research Oxford Biomedical Research Centre. No industry conflicts were disclosed.

Note: both the US FDA and CDC have been conducting COVID-19 vaccine candidate reviews since October 22, 2020. An updated listing of vaccine candidates is published on this webpage.

CoronavirusToday publishes COVID-19 Vaccine news.