October 21, 2020

expert reaction to feature on whether COVID-19 vaccine trials will be able to tell us if they prevent hospitalisations, intensive care use or deaths

A feature, published in the BMJ, discusses whether COVID-19 vaccine trials will be able to tell us if they prevent hospitalisations, intensive care use or deaths.

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

“These comments in the BMJ are questionable, although a number of their facts are correct.  The use of “surrogate” variables to indicate benefit in trials of drugs has previously been, in some cases, rightly criticised.  But in some cases such as with CD-4 counts in HIV they proved very useful.

“Trials of vaccines to show benefit in death or serious hospital outcomes would need to be absolutely massive (hundreds of thousands) and probably never complete because people would be reluctant to participate if the vaccine had already shown efficacy against infection.  Unlike other surrogates, infection is a necessary step along the path to death or other serious outcomes, and so is likely to be a good surrogate.  Certainly some trials have recruited people aged over 70, though there are probably relatively few if any above 85, so some vaccines will know if they work as well in the elderly.

“My view is that it would be best in future after new vaccines are introduced following initial trials that show efficacy against infection, for us to then continue with cluster randomised trials which could further measure their efficacy and safety.  Or if not, then very good surveillance, especially for safety, but also for efficacy, must be done.  Such follow-up is more possible today than it was in the past with good electronic health records.”

‘Will covid-19 vaccines save lives? Current trials aren’t designed to tell us’ by Peter Doshi was published in the BMJ at 23:30 UK time on Wednesday 21 October 2020.

DOI: 10.1136/bmj.m4037

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.”