How Vaccines Prove Their Safety

As acute and infectious disease neurologists, we are often asked if a vaccine is safe. Pfizer ’s announcement Monday that its Covid-19 vaccine is 90% effective makes the question even more pertinent. Earlier this year, two late-stage clinical trials, from Johnson & Johnson and AstraZeneca , were briefly paused after reports of neurological concerns in individual study participants. Each of these rare instances was carefully scrutinized as an adverse event—a serious clinical observation that requires review by the Data and Safety Monitoring Board.

At least two patients were initially thought to have developed transverse myelitis, a condition in which the patient’s immune system attacks the spinal cord. Similar autoimmune responses can affect the nervous system in conditions that mimic multiple sclerosis or Guillain-Barré syndrome, both of which can cause paralysis. Non-neurological complications such as anaphylaxis are also possible, related also to a vaccine’s misdirected effect on the immune system.

The purpose of listing potential adverse effects is not to create a list of reasons to avoid vaccines. These disorders are rare, and most cases spontaneously occur in otherwise healthy people who haven’t recently been vaccinated. Thus when a subject in a trial develops one of these disorders, it is often unclear whether the vaccine has anything to do with it.

In randomized clinical trials, industry sponsors and trial committees don’t necessarily know if a particular patient has received the vaccine. Patients and doctors often don’t know. Depending on the trial design, they might have received a placebo or an already approved vaccine as part of the control group. That means that in every one of these rare events, researchers must establish whether the afflicted patient received the Covid vaccine, another vaccine or no vaccine at all.

At the same time, a detailed review is required to characterize the event in the first place. Neurological diseases aren’t always straightforward: What looks like a seizure may turn out to be something else. It’s entirely possible that a given event is what it appears to be, and is a side effect of the vaccine. But since these diseases occur in the general population, one has to determine whether the clinical disease was likely related to the study intervention or not.