Adverse events: some terminology

One of the COVID vaccine trials sponsored by AstraZeneca has been ‘put on hold’ because of  a ‘suspected serious adverse reaction’.  What does that mean and how bad is it?

Some terminology

• Adverse Event (AE): a bad thing that happens to someone in a trial. These are not necessarily related at all to the trial treatment; something counts as an AE even if you’re getting placebo. They range from minor to serious
• Serious Adverse Event (SAE): the adverse event is hospital bad.  More precisely,  fatal, life-threatening, needing hospitalisation, or leading to significant permanent effect, or  could have gotten that way if it wasn’t stopped by treatment.
• Adverse Reaction (AR): an adverse event that was caused by the trial treatment. Some of the COVID vaccine candidates have quite a  lot of these; fever, for example.
• Serious Adverse Reaction: an SAE that was caused by the trial treatment
• Suspected Serious Adverse Reaction: an SAE that might have been caused by the trial treatment
• Suspected Unexpected Serious Adverse Reaction (SUSAR): an SAE that might have been caused by the trial treatment, and wasn’t disclosed to the participant as a reasonably expected result. (Some treatments do have expected serious adverse reactions — some cancer chemotherapy, for example)

It’s standard in clinical trials that you consider SSARs/SUSARs urgently, and for completely new treatments the consideration should be especially careful.  It might turn out on investigation that the event is unlikely to be caused by the treatment (eg, because of timing, or because you find a more likely cause); it might turn out that it is likely to be caused by treatment;  or everything might just be messily inconclusive.

If you have tens of thousands of people in vaccine trials then adverse events will occur, and some of the adverse events will be serious. That’s inevitable. If you have a treatment that could potentially cause a very wide range of adverse events, then some of the serious adverse events will inevitably look like they could have been caused by the treatment.  And, sometimes, they will have been.  Vaccines aren’t intrinsically safe; they are safe when approved because they get thoroughly investigated first.

The immediate question for the trial sponsor and investigators in this case is whether the adverse event, whatever it is, significantly changes the risk:benefit balance of the vaccine candidate, as explained to the study participants (and to the company’s investors).  So far, no-one knows, but AstraZeneca seem to be handling this appropriately, and there’s no obvious reason to expect that to change.