Investigating Serious Adverse Events in COVID-19 Vaccine Trials

23 November 2020

Despite the urgent need for a COVID-19 vaccine, it is of critical importance that the process of safety evaluation is not compromised in any way. All potential serious side effects (“adverse events”) that are observed during clinical trials of the new vaccines must be thoroughly reviewed, regardless of the expedited development schedule. Our new editorial in Drug Safety explains how all serious adverse events that occur during clinical trials are thoroughly and systematically investigated.

COVID-19 vaccine candidates have been developed at unprecedented speed, and there are currently a handful of vaccines in the final stages of clinical testing. Today it has been reported that the COVID-19 vaccine developed by Oxford University/ AstraZeneca is at least 70% effective in preventing infection with COVID-19. Other vaccine developers have recently reported that their new vaccines are 90 – 95% effective (BioNTech/ Pfizer, Moderna).

While it is important that vaccines are effective, it is absolutely essential that they are safe. Unlike medicines, vaccines are generally provided to healthy people, meaning that it is not ethical to release a vaccine for use unless it is as safe as it can possibly be. A key part of safety evaluation takes place during clinical trials before the vaccine is released for use in the general population.

The Drug Safety Research Unit has published an editorial in Drug Safety which explains the process of investigating any serious adverse events that occur during clinical trials. This is the process that would be followed during clinical trials for the new COVID-19 vaccines that led to recent pausing of Phase III trials for both the AstraZeneca and Johnson & Johnson vaccines following reports of safety concerns.

A key aspect of evaluation of serious adverse events observed during clinical trials is to determine whether the event is likely to be linked to the vaccine (causality) or whether there is another explanation. Once the adverse event has been diagnosed, the reviewer will work through an algorithm to determine (a) whether there is evidence for other (non-vaccine) causes, (b) whether events of this type are known to be typically linked to vaccination, (c) whether there is strong evidence against a link with the vaccine, and (d) any other factors including previous medical history.

Safety evaluation during clinical trials is a critical component of the robust safety measures implemented during development of the new COVID vaccines. Together with continued thorough safety monitoring once the vaccines are licensed for use in the general population, it is hoped that these measures will increase confidence in the vaccines in the general public.

The editorial can be accessed here: https://link.springer.com/article/10.1007/s40264-020-01018-y