Risk/benefit assessment

Continuous evaluation of risks and benefits of vaccines is required to strengthen the confidence in immunization programmes. In Module 1 you looked at the need to balance vaccine efficacy and vaccine safety by conducting risk/benefit assessments.

On this page, let us look at how risk/benefit assessments are conducted and acted upon. A risk/benefit assessment should:

  • Address the population at risk (not the individual at risk),
  • Take into account contextual issues (economics, availability of alternative vaccines, sociopolitical and cultural factors),
  • Be prompted by a newly identified risk, but must remain holistic (e.g. take into account the entire safety profile of a vaccine, not only the specific information relating to the event that was detected),
  • Run in parallel to active enquiry, cooperation and exchange of information. 

The need for urgent action should be weighed against the need for further investigation; the question below illustrates this principle.

Question

Think about this example:

During a mass measles campaign for 7.5 million children aged from 9 months to 14 years, a 7-year-old child developed encephalopathyEncephalopathyRefers to a variety of conditions affecting the brain resulting in alterations in the level of consciousness, ranging from stupor to coma. At times, febrile seizures, afebrile seizures, and epilepsy have been considered components of encephalopathy. However, the terms encephalopathy and encephalitis have been used imprecisely and even interchangeably in the literature., convulsionsSeizureUncontrolled electrical activity in the brain, resulting in convulsion, physical signs, thought disturbances, or a combination of symptoms. and died.

Should the measles campaign be suspended?
Does the need for action to protect children from possible vaccine-related harm in this situation outweigh the need for further investigation, or vice versa?

Click on the below to see what action was taken in response to the event.

Answer

The case was isolated and clinical & laboratory investigations were carried out. A brain biopsy was collected immediately after the child’s death and sent for culture, microscopy and electronic microscopy. It was determined that herpes virus was responsible for the clinical picture. This example shows, that it is critical to take additional information into account.

Apart from the additional information that was made available, one has to be aware, that the nature of the problem is also a potential factor:

  • Disease level and incidence – is this a common vaccine-preventable condition (e.g. measles) or relatively rare (e.g. diphtheria)?
  • Is this a crisis situation – for example, a life-threatening vaccine reaction or a threat to the continuation or success of the immunization programme?
  • Is the risk caused by an immunization error that can be identified and corrected, or is it an unavoidable and inherent risk?
  • Why has concern been raised about the risk and by whom?

Benefit evaluation begins with an understanding of the epidemiology and natural history of a vaccine-preventable disease in the unvaccinated population. It involves evaluating the size of the reduction in risk of morbidity and mortality from the disease in the vaccinated population, which is dependent on the efficacy of the vaccine used.

The following table may help to break down some of the various aspects when evaluating the benefits versus the risks.

BENEFIT EVALUATION RISK EVALUATION
  • Description of implicated vaccine and lots (incl. brand, manufacturer, lot, international use).
  • Indications for use (e.g. reduce risk of morbidity and mortality associated with measles or rotavirus cases by 80%).
  • Identification of alternative modalities (if any, e.g. vitamin A supplementation, behaviour modification etc).
  • Brief description of safety of vaccine.
  • Epidemiology and natural history of disease (e.g. morbidity and mortality of rotavirus disease).
  • Known efficacy of vaccine used.
  • Weight of evidence for suspected risk (e.g. frequency, severity, mortality of anaphylaxis).
  • Detailed presentation and analysis of data on new suspected risk (results of case investigation, incidence in campaign).
  • Probable and possible explanations.
  • Preventability, predictability and reversibility of new risk (e.g. is it the same as known risk of measles vaccine?).
  • Risks of alternative vaccines.
  • Review of complete safety profile of vaccine.
  • Estimation of excess incidence of any AEFI common to alternatives.
  • Highlighting of important differences between alternatives.

Considering the options for action

As a result of the risk/benefit assessment, an options analysisOptions analysisA system for ranking multiple options in order to decide the best course of action in the prevailing circumstances. should list all appropriate options for follow-up action.

Example: Options for action could include discontinuing the immunization campaign, withdrawing a vaccine batch, and improving staff training and communication.

The options analysis should describe the advantages and disadvantages of each option and the likely consequences.

Example: Withdrawing a vaccine lot:

  • Advantages: reduces fear of vaccine, renews confidence in the vaccine or the campaign,
  • Disadvantages: cost, potential compromise of the campaign, loss of confidence in vaccine quality.

Finally, the options analysis should outline plans or suggestions of studies that could help to determine the best course of action.

Example: Audit injection practices of health workers to identity possible sources of immunization errors; investigate the need for improved training and education.

It is essential to indicate the quality and quantity of any future evidence necessary to trigger reconsideration of the issue, and how the outcomes of any actions will be monitored and assessed.

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