Balancing efficacy and safety
Vaccine efficacy refers to the ability of a vaccine to bring about the intended beneficial effects on vaccinated individuals in a defined population under ideal conditions of use. The potential benefits of an effective vaccine – e.g. promotion of health and well-being, and protection from illness and its physical, psychological and socioeconomic consequences – must be weighed against the potential risk of an adverse event following immunization (AEFI) with that vaccine. Vaccine-associated risk is the probability of an adverse or unwanted outcome occurring, and the severity of the resulting harm to the health of vaccinated individuals in a defined population following immunization with a vaccine under ideal conditions of use.
Public confidence in vaccine safety is increased by clear communication of risk/benefit assessments, comparing the very low vaccine-associated risk with the very significant benefits of vaccination.
Weighing the risks and benefits of a vaccine
An important criterion of vaccine safety that regulatory authorities must establish is the risk/benefit assessment of immunization with a particular vaccine in a defined population. You will learn how to conduct a risk/benefit assessment in Module 4 'Surveillance' and about the actions that follow the identification of an increased or new vaccine risk. Here we introduce you to some basic principles and the issues that regulatory authorities consider when balancing vaccine efficacy and vaccine safety.
Risk evaluation for a specific vaccine requires the collection and analysis of reliable data on:
- the identified safety signals;
- the identified risk factors (specific population);
- the incidenceIncidenceThe number of new cases (e.g., of a disease, adverse event) occurring in a defined population during a given time interval, often one year., severity, morbidity and mortality resulting from adverse vaccine (product-related) reactions;
- case investigation to determine whether the vaccine presents a new suspected risk;
- the probable mechanism and underlying cause of any vaccine reactions;
- the preventability, predictability and reversibility of the risk of a vaccine reaction occurring;
- the risks associated with alternative vaccines that protect against the same disease;
- the risks associated with not vaccinating, i.e. the risks arising from the infectious disease in unvaccinated individuals. The table below illustrates this point very clearly for measlesMeaslesA contagious viral disease marked by fever, the eruption of red circular spots on the skin that can be ￼￼￼￼￼￼deadly to young and weakened individuals..
Summarizing the risk/benefit relationship of a vaccine in tables and diagrams is useful to:
- relate the benefits to the seriousness of the target disease;
- focus key messagesKey messageA key message gives the most important information that you want the public to know, for example in relation to a health education campaign on the benefits of vaccination. on vaccine efficacyVaccine efficacyThe potential of a vaccine to protect from a disease in controlled clinical trials. Expressed as a percent. and safety in vaccination campaigns and routine immunization programmes;
- alert healthcare staff to the dominant risks associated with a vaccine and the probability of an adverse vaccine reaction occurring;
- encourage consideration of alternative vaccines which may offer greater efficacy and/or safety.
Risk of acquiring illnesses following infection versus risk following vaccination
|Measles infectiona||Measles vaccineb|
|Otitis||7 – 9%||0|
|Pneumonia||1 – 6%||0|
|Post-infectious encephalomyelitis||0.5/1 000||1/100 000 – million|
|Anaphylaxis||0||1/100 000 – million|
|Thrombocytopenia||Not properly quantifiedc||1/30 000d|
|Death||0.1 – 1/1 000 (up to 5 – 15%)||0|
a Risks after natural measles are calculated in terms of events per number of cases.
b Risks after vaccination are calculated in terms of events per number of doses.
c Although there have been several reports of thrombocytopenia occuring after measles including bleeding, the risk has not been properly quantified.
d This risk has been reported after MMR vaccination and cannot be only attributed to the measles component.
MMR = measles, mumps and rubella; SSPE = subacute sclerosing panencephalitis.
P. Duclos, BJ Ward. Measles Vaccines, A Review of Adverse Events, Drug Safety 1998; Dec 19 (6): 435—454
Risk/benefit assessments should be applied to most situations relating to the efficacy or safety of vaccines to ensure public safety and public health.