Reactogenicity

In clinical trials, the term reactogenicity refers to the property of a vaccine of being able to produce common, “expected” adverse reactions, especially excessive immunological responses and associated signs and symptoms—fever, sore arm at injection site, etc. (Much less frequently, the term has also been applied to therapeutic drug trials.) Other manifestations of reactogenicity typically assessed in such trials include bruising, redness, induration, and swelling.

The term reactogenicity was coined by the US Food and Drug Administration (FDA). Typically, reactogenicity is seen in the presence of an adjuvant (chemical additive intended to enhance the recipient's immune response to the vaccine antigen), but can also occur with non-adjuvanted vaccines. Reactogenicity describes immediate short-term reactions to vaccines, not long term sequelae. Assessments of reactogenicity are carried out to evaluate the safety and usability of an experimental vaccine (see Investigational New Drug). It is unclear whether a higher degree of reactogenicity to a vaccine actually correlates with more severe adverse events, such as would require hospitalization or be life-threatening. Occasionally they do, but this could be an accidental concurrence. After many years of assessing large databases relating to these events, the FDA has not been able to make any such association.

Formal definitions

The US National Institutes of Health (NIH) has provided the following “definition of reactogenicity” in a suggested template for clinical trials protocols:^[1]

Reactogenicity events are adverse events that are common and known to occur for the intervention/investigational product being studied and should be collected in a standard, systematic format using a graded scale based on functional assessment or magnitude of reaction. Provide a definition of expected vs. unexpected AEs and local vs. systemic events, based on the risk profile of the intervention/investigational product. This information is found on the CIB or package insert. Typically, reactogenicity adverse events are solicited and collected on diary cards or a reactogenicity case report form.

Example of a functional scale for assessing reactogenicity or other parameters not specifically listed in the toxicity table:

0 = Absence of the indicated symptom

1 = Mild (awareness of a symptom but the symptom is easily tolerated)

2 = Moderate (discomfort enough to cause interference with usual activity)

3 = Severe (incapacitating; unable to perform usual activities; requires absenteeism or bed rest)

4 = Life-threatening

References

1. NIH (2004), [glrce.org/docs/NIH%20Clinial%20trial%20protocol%20template.doc DIMD Protocol Template].