Collaboration and standardized approaches for assessing different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy endpoints will be important to ensure that the most effective candidates for a vaccine are deployed, according to a review published in Lancet Infectious Diseases.
A SARS-CoV-2 vaccine that can reduce infection, disease, or transmission would play an extensive role in controlling the coronavirus disease 2019 (COVID-19) pandemic. However, the most important efficacy endpoint will be the vaccine’s ability to protect against severe disease and mortality, since this places the greatest burden on healthcare systems. Determining whether a vaccine can protect against severe disease and death from COVID-19 may not be possible in phase 3 clinical trials and will often require long-term, ongoing studies after widespread deployment of a vaccine.
To ensure ongoing evaluation of vaccine safety, well-supported pharmacovigilance studies after licensure will be necessary. Clinical trials will likely be insufficiently powered to detect vaccine-associated enhanced respiratory disease or serious adverse events.
Investigators note that measuring outcomes such as reduced infection, transmission, or disease rates, which rely on laboratory assays like the quantitative reverse transcription polymerase chain reaction (RT-PCR) assay, is imperfect. Currently, sensitivity and specificity of any quantitative RT-PCR assay and any serological assay for SARS-CoV-2 infection is unknown due to the lack of a validated gold standard for diagnosis. Since many vaccines are aiming to induce antibodies, serological assays will need to be able to differentiate antibodies induced by infection from those induced by vaccination.
Although controlled human infection studies might provide the only means of rapidly assessing vaccine efficacy, it is unclear if results from these studies, which are likely to only include young volunteers, will predict vaccine efficacy in older population.
Dedicated trials will also be needed to assess vaccine efficacy in patients under 18 years of age. Trial data in adults may not be predictive of vaccine safety and efficacy in this age group. However, before pediatric vaccine studies are initiated, investigators should have a greater understanding of the biology of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection.
According to investigators, it is unlikely that there will be a single vaccine winner, especially given the challenges of manufacturing and supplying a single vaccine at large scale initially. Given the political and media scrutiny of the development of SARS-CoV-2 vaccines, “it is imperative that efficacy outcomes for a SARS-CoV-2 vaccine are critically appraised with scientific rigor to understand their generalizability and clinical significance,” investigators concluded.
Hodgson SH, Mansatta K, Mallett G, Harris V, Emary KRW, Pollard AJ. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect Dis. Published online October 27, 2020. doi:10.1016/S1473-3099(20)30773-8