Case Study: Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination (interactive) Composite page for printing

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Study Source
Context
Use of biological weapons by terrorists is increasingly a concern in the United States.
Smallpox is one of the likely biological agents that have drawn the attention of the federal government. The U.S. federal government is producing and stockpiling smallpox vaccine in response to the threat.
In spite of its effectiveness, the vaccine contains a live virus that can potentially result in serious complications.
This study is an appraisal of the risks and benefits faced by a person living in the United States. It is designed to aid public officials in understanding the factors that affect the public's decision-making process regarding smallpox vaccination programs.
Methods
Societal
A computer-based risk-benefit model that compares the risk of smallpox disease with the potential failure of the vaccine or vaccine-related adverse events.
Four different target populations were considered; the entire US population, population of a representative large U.S. city, health-care workers ( HCWs), and a smallpox investigation team.
Definitions of Key Terms
  • Disease refers to patients with clinical symptoms caused by either smallpox or serious vaccine-related adverse events.
  • Serious vaccine-related adverse events include death, postvaccinial encephalitis, and progressive vaccinia. Serious vaccine-related adverse events are those that require medical care (e.g., vaccinia immunoglobulin, hospitalization, or a number of visits to a physician's office).
  • For the purpose of this study, vaccine-related adverse events such as eczema vaccinatum, soreness, or redness at site of vaccination, headache, and mild and temporary nausea were NOT considered as serious vaccine-related adverse events in the model.
The Model
The Three Scenarios
  1. General population: For a member of the general population, the model compares the risk to a person of being infected with smallpox before an attack is detected to the risk of a person having serious vaccine-related adverse events.
  2. Hospital personnel: For a health-care worker who faces potential exposure to smallpox as a result of attending to a person with smallpox, the risk of contracting smallpox from that patient is compared with the risk for serious vaccine-related adverse events.
  3. Investigation team: For a member of a smallpox investigation team who is trained to be deployed to investigate potential patients or attacks, the risk of contracting smallpox from a patient or other source of smallpox (e.g., aerosol, container) is compared with the risk for serious vaccine-related adverse events.
Assumptions
  • The higher the probability of infection, the more risky the situation. Therefore, probabilities are used as numerical measures of risk.
  • Throughout the analysis, the assumption is made that appropriate responses are implemented after the attack has been detected.
  • The net risk of disease is:
    Net risk of disease = Risk from smallpox without preexposure vaccination ( Risk of smallpox attributable to vaccine failure + Risk of vaccine-related adverse events from preexposure vaccination )
    Net risk of disease = ( PR x PE x PT ) - [ ( PR x PE x PT ) ( 1 - PVEpre ) + ( PSideEffect x PValuation ) ]
    Where:
    PR = the probability of attack
    PE = the probability of exposure to smallpox for an individual in the different groups
    PT = the probability of transmission for an individual in the different groups
    PVEpre = the probability of preexposure vaccine effectiveness
    PSideEffect = the probability of serious vaccine-related adverse events
    PValuation = a relative measure used to factor in people's valuation of vaccine side effects
    Please refer to the following table for detailed definitions of all the variables.
    Model input variables and values used
      Values
    Variable Symbol Base cases Sensitivity analyses
    Probability of attack PR 1:10–1:100,000  
    No. of cases before detection of attack XCASE 1,000 100,000
    General population "at risk" XPOP 9 million or 280 million  
    No. of susceptible health-care workers (HCWs) XHCW 100,000 or 1,000,000  
    Probability of exposure to smallpox PE    
    • Individual member of general populace
      1:9,000 or 1:280,000 1:1
    • Individual HCW contacting infectious person
      1:100 or 1:100,000 1:1
    • Individual member of investigation team
      1:2.5 or 1:5 1:1
    Probability of transmission of smallpox PT    
    • Individual member of general populace
      1.0 0.01–0.70
    • Individual HCW contacting infectious person
      0.70 0.01–0.70
    • Individual member of investigation team
      0.40 0.01–0.70
    Probability of vaccine effectiveness, preexposure PVEpre 0.98  
    Probability of serious vaccine-related adverse events PSideEffect 1:100,000 1:500–1:1,000,000
    Probability of vaccine effectiveness, postexposure PVEpost   0.01–0.60
    Relative individual valuation:
    Case of smallpox :   Case(s) of serious vaccine-related adverse events
    PValuation 1:1 1:35
    Table notes:
    • Risk of exposure for a member of the general populace is defined as the risk of contracting, and subsequently developing, a clinical case of smallpox before detection of the event. For an individual in the general populace:
      PE = XCASE / XPOP
    • Risk of HCWs becoming exposed is a function of the number of cases divided by number of susceptible HCWs:
      PE for HCW = XCASE / XHCW
    • For the base case, a person is assumed to value one case of smallpox as one serious vaccine-related adverse event:
      PValuation is 1:1
Decision Rule
The decision criteria can lead to two possible outcomes;
  1. If the net risk is greater than zero, it implies that the risk from preexposure to smallpox is greater than the risk from infection attributable to vaccine failure or the risk of vaccine-related events. In this situation, the person will opt for vaccination.
  2. If the net risk is less than zero, it implies that the risk of smallpox vaccine failure or vaccine-related events is greater than the risk of smallpox attack without preexposure vaccination. In this situation, the person will decline vaccination.
Interactive Exercises
You can use the interactive exercises below to calculate the risks and benefits for alternative options in each of the three scenarios.
The model simulation is based on the net risk of disease equation described in the earlier AssumptionsOpen this in a new window section.
Variable descriptions are provided in the earlier Model input variables and values usedOpen this in a new window table.
Exercise 1. General Population
Instructions
You can change the values of the variables in the second column of the spreadsheet below. After you change a value, you can recalculate the result by:
  • moving the cursor to a different variable, or
  • clicking the "Calculate" button.
If there are zero-valued variables, we show them and the result in yellow.
Press the "Reset" button to restore all the variables to their original values.
Description Values   Range
Probability of attack 1-in-  10–100,000
Number of persons infected before detection of attack 1,000–100,000
Susceptible population 9,000,000–280,000,000
Probability of vaccine effectiveness, preexposure 0.70–1.00
Probability of serious vaccine-related adverse events 1-in-  500–1,000,000
Relative individual valuation of a case of smallpox versus serious vaccine-related adverse events :  1–35
 
THE RESULT: Recommend preexposure vaccination? Yes
Exercise 2. Hospital Personnel
Instructions
You can change the values of the variables in the second column of the spreadsheet below. After you change a value, you can recalculate the result by:
  • moving the cursor to a different variable, or
  • clicking the "Calculate" button.
If there are zero-valued variables, we show them and the result in yellow.
Press the "Reset" button to restore all the variables to their original values.
Description Values   Range
Probability of attack 1-in-  10–100,000
Number of infected seeking medical care before detection of attack 1,000–100,000
Number of health-care workers 100,000–1,000,000
Probability of transmission 0.01–0.70
Probability of vaccine effectiveness, preexposure 0.70–1.00
Probability of serious vaccine-related adverse events 1-in-  500–1,000,000
Relative individual valuation of a case of smallpox versus serious vaccine-related adverse events :  1–35
 
THE RESULT: Recommend preexposure vaccination? Yes
Exercise 3. Investigation Teams
Instructions
You can change the values of the variables in the second column of the spreadsheet below. After you change a value, you can recalculate the result by:
  • moving the cursor to a different variable, or
  • clicking the "Calculate" button.
If there are zero-valued variables, we show them and the result in yellow.
Press the "Reset" button to restore all the variables to their original values.
Description Values   Range
Probability of attack 1-in-  10–100,000
Probability of contact with smallpox by team member 0.20–1.00
Probability of transmission 0.01–0.70
Probability of vaccine effectiveness, preexposure 0.70–1.00
Probability of serious vaccine-related adverse events 1-in-  500–1,000,000
Relative individual valuation of a case of smallpox versus serious vaccine-related adverse events :  1–35
 
THE RESULT: Recommend preexposure vaccination? Yes
Overall Recommendations
For the values showing in the spreadsheets in the sections above, we have these recommendations for preexposure smallpox vaccinations:
The general populace Yes
Hospital personnel Yes
Investigation teams Yes
Results
For a person in the general population of 280 million, the net risk is negative. The risk of serious vaccine-related events is greater that the risk of attack without vaccination. This is also true when the risk of attack is as high as one in 10, therefore an individual would decline preexposure vaccination.
The net risk is positive when the population is 9 million and the risk of attack is one in 10. In this situation, the individual would opt for preexposure vaccination.
The risk for an infectious case of smallpox must be at least one in 100 and the probability of attack causing 1,000 cases must be greater than one in 1,000 for a health-care worker (HCW) to accept preexposure vaccination.
If the risk for contact drops to one in 1,000, then the risk for attack must be more than one in 100 for an HCW to accept vaccination.
For a member of an investigation team, if anticipated risk for contact is one in 2.5 and the risk for attack is at least one in 16,000, then a member of the team would opt for preexposure vaccination.
However, if the risk is reduced to one in 5, then the risk of attack must be at least one in 8,000 for a member of the team to accept preexposure vaccination.
Sensitivity Analysis
A member of the general U.S. population would accept preexposure vaccination only when:
  • the person:
    • believes the risk of smallpox attack to be one in 10, and
    • values one case of smallpox at 35 cases of serious vaccine-related adverse events (PValuation is 1:35),
  • or the person:
    • believes the risk of smallpox attack to be reduced to one in 100, and
    • values one case of smallpox at 290 cases of serious vaccine-related adverse events,
  • or the person:
    • believes that the initial attack would cause 100,000 cases before detection,
    • values a case of smallpox at 35 cases of serious vaccine-related adverse events, and
    • believes the risk of smallpox attack to be more than one in 1,000.
For a person in a population of 9 million:
  • If the person believes that the risk of serious vaccine-related adverse events is one in 10,000, then she would not accept preexposure vaccination even if the risk of attack were one in two.
  • If the person:
    • believes that the risk for adverse events is one in 10,000,
    • believes that the number of cases is 100,000, and
    • values a case of smallpox at 35 cases of vaccine-related adverse events,
    then the risk of smallpox attack would have to be more than eight in 1,000 for her to accept preexposure vaccination.
A member of the general U.S. population would not accept preexposure revaccination if:
  • the risk of serious vaccine-related events is one in 1,000,000,
  • the risk of smallpox attack is one in 10,
  • there are 1,000 cases before discovery, and
  • PValuation is set at 1:1.
If PValuation is changed to 1:35, then the risk for smallpox attack would have to be more than one in 125 for the person to accept preexposure revaccination.
An HCW would accept preexposure vaccination if:
  • the risk of smallpox attack is greater than one in 700,
  • the risk for contact is one in 1,000,
  • PValuation is 1:1, and
  • revaccination PSideEffect is one in 1,000,000.
If the HCW believes that the risk for contact has increased to one in 100, then the risk of smallpox attack would have to be more than one in 7,000 for her to accept revaccination.
Assuming that a person has had contact with another person but is uncertain (i.e. the person she comes into contact with might be infectious), then she would accept postexposure vaccination if:
  • the risk for exposure is greater than or equal to one in 21,000,
  • the risk of transmission is believed to be 35%, and
  • the efficacy of postexposure vaccine is assumed to be 60%.
If the risk for transmission is increased to 70% and the postexposure vaccine efficacy is only 10%, then vaccination would be accepted if the risk of exposure is more than one in 8,000.
Policy Implications
The study revealed that the single most influential variable is the risk of smallpox attack. This indicates that the public's perception of the risk confronting them is relevant.
Thus although a person's risk cannot be fully characterized by numerical analyses, it is a fact that individuals make decisions based on the perceived risks and benefits of alternative choices available to them.
To that extent, health planners and medical care providers need to appreciate individuals' valuations of the risks and benefits associated with the program.
This will make officials aware of the factors that affect their decisions and also help them to explain how improvements in technology and other conditions would affect the risk and benefits for the individuals.
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