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Source: United Kingdom – Executive Government & Departments

A review piece, published in The Lancet Infectious Diseases, looked at the challenges in assessing the clinical efficacy of vaccines against SARS-CoV-2.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This review should be essential reading for all those who are wishing to make assessment of vaccines to prevent Covid-19.

“It covers all the important issues, written by a group that is very familiar with one particular trial in Covid-19 but the group have very extensive experience of trials of other vaccines.

“It makes it very clear that the ultimate aims of preventing serious illness and death are the most important ones.  However it also makes clear that the numbers needed in trials to show benefit on these outcomes are simply far too large to be feasible.  After phase 3 trials we should know how effective vaccines are at stopping or reducing infection and transmission, and only those vaccines that are effective and safe on these criteria will be licensed.  It is likely that efficacy for prevention of infection will extend to benefits for more serious outcomes, but this is not certain.  It will then require further follow up, once vaccines are in use, to confirm benefits in terms of serious illness and death and to add evidence on the magnitude of those benefits.  They note that it will also be important to ensure efficacy in subgroups like the elderly or, eventually, in children.  The vital point is that there needs to be consistent and standardised follow-up of those vaccinated once a vaccine starts to be used.

“They note that some countries may license or use a vaccine without even evidence of prevention of infection, but only based on blood tests showing possible protection through the immune response seen.  The US, and the EU have made it clear that they will require clinical evidence and that is likely to be true in the UK.

“While the evidence after phase 3 trials is going to be satisfactory for the outcome of clinical infection, the further follow up to confirm that the benefit extends to serious illness and death will depend on observational studies.  The authors, in making this distinction between outcomes clear, might have paid insufficient attention to the problem, even with standardised follow-up in a non-randomised setting, that answers will be inevitably uncertain.  If randomisation could be employed during the introduction of new vaccines (cluster randomised or stepped wedge-design trials) then this would be very beneficial both in the assessment of efficacy but even more for safety.”

‘What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2’ by Susanne H Hodgson et al. was published in the Lancet Infectious Diseases at 23:30 UK time on Tuesday 27 October 2020.

DOI: 10.1016/S1473-3099(20)30773-8

Declared interests

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.”

MIL OSI United Kingdom