(Case) Risks & Benefits of Smallpox Vaccination

Study Source

"Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination"

by Martin L. Meltzer, Emerging Infectious Diseases

vol. 9, No.11, November 2003.

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.

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

=

(

P_R

x

P_E

x

P_T

)

-

[

(

P_R

x

P_E

x

P_T

)

(

1

-

P_VEpre

)

+

(

P_SideEffect

x

P_Valuation

)

]

Where:

P_R	=	the probability of attack
P_E	=	the probability of exposure to smallpox for an individual in the different groups
P_T	=	the probability of transmission for an individual in the different groups
P_VEpre	=	the probability of preexposure vaccine effectiveness
P_SideEffect	=	the probability of serious vaccine-related adverse events
P_Valuation	=	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

P_R

1:10–1:100,000

No. of cases before detection of attack

X_CASE

1,000

100,000

General population "at risk"

X_POP

9 million or 280 million

No. of susceptible health-care workers (HCWs)

X_HCW

100,000 or 1,000,000

Probability of exposure to smallpox

P_E

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

P_T

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

P_VEpre

0.98

Probability of serious vaccine-related adverse events

P_SideEffect

1:100,000

1:500–1:1,000,000

Probability of vaccine effectiveness, postexposure

P_VEpost

0.01–0.60

Relative individual valuation:

Case of smallpox

:

Case(s) of serious vaccine-related adverse events

P_Valuation

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:

P_E = X_CASE / X_POP
Risk of HCWs becoming exposed is a function of the number of cases divided by number of susceptible HCWs:

P_E for HCW = X_CASE / X_HCW
For the base case, a person is assumed to value one case of smallpox as one serious vaccine-related adverse event:

P_Valuation is 1:1

Decision Rule

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 Assumptions

section.

Variable descriptions are provided in the earlier Model input variables and values used

table.

Exercise 1. General Population

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 :	1–35

THE RESULT: Recommend preexposure vaccination?	Yes

Exercise 2. Hospital Personnel

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 :	1–35

THE RESULT: Recommend preexposure vaccination?	Yes

Exercise 3. Investigation Teams

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 :	1–35

THE RESULT: Recommend preexposure vaccination?	Yes

Overall Recommendations

Results

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 (P_Valuation 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
P_Valuation is set at 1:1.

If P_Valuation 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,
P_Valuation is 1:1, and
revaccination P_SideEffect 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

Study perspective	Societal
Study design	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.
Target population	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.

The general populace	Yes
Hospital personnel	Yes
Investigation teams	Yes