In an opinion piece published in CNS Drugs, researchers highlighted the need for rapid investigations of vaccine safety concerns to use robust epidemiologic methods to maintain public and professional confidence in vaccination programs.1
The aim of this paper was 2-fold. First, researchers described the 4 statistical methods most commonly used to address vaccine safety questions and their merits. Second, they evaluated the relationship between vaccinations and neurologic diseases, specifically multiple sclerosis, Guillain-Barré syndrome, and narcolepsy, using the latest epidemiologic evidence.
The 4 statistical methods evaluated were the cohort, case-control, case-coverage, and self-controlled case-series methods. While the self-controlled case-series method has become the gold-standard design in vaccine safety studies due to the advantage of controlling for various confounding factors, researchers stressed that “for each study question the methods should be adapted and potential biases considered in the context of the population under study, the dataset being utilized, and the hypothesis being tested.”
With regard to neurologic conditions, there is a long history of causal associations with vaccination being inferred from temporally related onsets. Following a mass hepatitis B vaccine campaign in 1994 in France, cases of multiple sclerosis with onset or relapse after vaccination were reported. However, the evidence has not supported an association between multiple sclerosis and the hepatitis vaccine.
Adolescence is an age at which autoimmune diseases, such as Guillain-Barré syndrome, are often diagnosed. While the evidence suggested there may be a small elevated risk of developing Guillain-Barré syndrome after influenza vaccines, this risk is considerably lower than the risk of developing the disorder after a natural influenza virus infection. Regarding the risk of developing Guillain-Barré syndrome with the human papillomavirus vaccine, another vaccine given during adolescence, the evidence suggests no elevated risk.
There is strong evidence of a causal association between narcolepsy with 1 adjuvanted vaccine used in the 2009/2010 influenza pandemic. A study published in 2013 using the self-controlled case-series method identified a 14-fold increased risk for narcolepsy and Pandemrix,™ with the attributable risk estimated to be 1.9 per 100,000 doses.2 “The now established association between narcolepsy and Pandemrix™ should act as a lesson for the vaccine safety community that sometimes unexpected but serious conditions can arise and need to be investigated rapidly however biologically implausible,” stated the researchers.
“As new vaccines are introduced, the basis of discussions on vaccine safety should be the acceptance that vaccination can carry a small risk but that this risk needs to be balanced against the enormous individual and public health benefits,” concluded the researchers.
1. Stowe J, Andrews N, Miller E. Do vaccines trigger neurological diseases? Epidemiological evaluation of vaccination and neurological diseases using examples of multiple sclerosis, Guillain-Barré syndrome and narcolepsy [published online October 1, 2019]. CNS Drugs. doi:10.1007/s40263-019-00670-y
2. Miller E, Andrews N, Stellitano L, et al. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ. 2013;346:f794.