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InfluenzaRiskAssessmentToolIRAT_PandemicInfluenzaFlu_CDC.pdf

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In�uenza Risk Assessment Tool (IRAT) Questions & Answers Please see this summary of In�uenza Risk Assessment Tool (IRAT) results for more information.

What is the In�uenza Risk Assessment Tool (IRAT)? The In�uenza Risk Assessment Tool (IRAT) is an evaluation tool developed by CDC and external in�uenza experts that assesses the potential pandemic risk posed by in�uenza A viruses that currently circulate in animals but not in humans. The IRAT assesses potential pandemic risk based on two di�erent questions regarding “emergence” and “public health impact.” These questions are listed as follows:

“Emergence” asks the question: What is the risk that a virus not currently circulating in the human population has potential for sustained human-to-human transmission? “Emergence” refers to the risk of a novel (i.e., new in humans) in�uenza virus acquiring the ability to spread easily and e�ciently in people.

“Public health impact” asks the question: If the virus were to achieve sus tained human-to-human transmission, what is the risk that a virus not currently circulating in the human population has the potential for signi�cant impact on public health? “Public health impact” refers to the potential severity of human disease caused by the virus (e.g., deaths and hospitalizations) as well as the burden on society (e.g., missed workdays, strain on hospital capacity and resources, and interruption of basic public services) if a novel in�uenza virus were to begin spreading e�ciently and sustainably among people.

The IRAT uses 10 risk elements to measure the potential pandemic risk associated with each of these questions. These 10 risk elements can be grouped into three overarching categories: “properties of the virus,” “attributes of the population,” and “ecology & epidemiology of the virus.” In�uenza subject matter experts evaluate novel in�uenza viruses based on each of these 10 risk elements. Each of the 10 risk elements is then weighted statistically based on its signi�cance to each of the two questions. A composite score for each virus is then calculated based on the given question. These composite scores provide a means to rank and compare in�uenza viruses to each other in terms of their potential pandemic risk for each of the two questions.

As we learn more about in�uenza A viruses, these 10 risk elements may change, other risk elements may be added or some current risk elements may be dropped. The IRAT is designed to be �exible and responsive to current scienti�c advances.

Can the IRAT predict a future pandemic? No. The IRAT is an evaluative tool, not a predictive tool. In�uenza is unpredictable, as are future pandemics.

What is the purpose of the IRAT? The IRAT is intended to do the following:

Prioritize and maximize investments in pandemic preparedness by helping to determine which novel (new) in�uenza viruses to develop vaccines against and capitalizing on surveillance e�orts and in-country capacity building activities;

Identify key gaps in information and knowledge which can be the basis to prompt additional studies (for example, if information is not available for one of the 10 risk elements used by the IRAT additional studies could be done or resources allocated to provide the missing information);

Document in a transparent manner the data and scienti�c process used to inform decisions associated with pandemic preparedness;

Provide a �exible means to uniformly and regularly update the risk assessment of a novel in�uenza virus as new information becomes available;

Be an e�ective evaluation tool for public health and medical professionals;

Provide a means to weigh the 10 risk elements di�erently depending on whether the intent of the risk assessment is to measure the ability of an in�uenza virus to “emerge” as a pandemic capable virus (i.e., become capable of e�cient human-to-human spread) or “impact” the human population if it did emerge.

Does the IRAT have any limitations? Yes. The IRAT cannot predict the next pandemic and is not intended to do so. Additionally, the IRAT depends on subject matter experts to carefully analyze the 10 risk elements of the IRAT to make determinations of pandemic risk and to rank the importance of the risk elements according to the speci�c risk question or situation. Lastly, the IRAT is not intended to provide a precise measurement of risk. For example, many risk assessments generate a quantitative measure that describes the likelihood of exposure or disease risk. The IRAT focuses on the perceived pandemic potential of novel in�uenza viruses as estimated by subject matter experts using the IRAT risk elements and available data. The IRAT depends on data that are often scarce and/or preliminary (for example, typically when the IRAT is run, there are a small number of cases of human infection which may not provide a reliable estimate of public health impact).

What are the risk elements used by the IRAT? The IRAT consists of 10 risk elements grouped within three overarching categories. These categories and risk elements are described as follows:

The “Properties of the Virus” category contains four of the 10 risk elements, including: 1. Genomic analysis is a measure of the extent of genetic diversity or presence of known molecular signatures important for human infections and disease.

2. Receptor binding refers to the host preference (e.g., animal or human) of an in�uenza virus as well as the types of tissues and cells the virus is best suited to infecting (e.g., nose tissue and cells vs. deep lung tissue and cells). Some in�uenza viruses are better adapted to infecting humans as opposed to animals.

3. Transmission in animal models is a measure of the ability of an in�uenza virus to transmit e�ciently in animals in laboratory studies. Some in�uenza viruses can transmit through the air via small infectious droplets expelled through coughs or sneezes, whereas other in�uenza viruses may only spread through direct contact with an infected host.

4. Antiviral treatment options refers to the predicted e�ectiveness of in�uenza antiviral medications, such as oseltamivir, zanamivir, baloxavir, and M2 blockers.

The “Attributes of the Population” category contains three of the 10 risk elements, including: 5. Population immunity refers to whether the human population has any existing immune protection against the novel in�uenza virus being evaluated. Susceptibility to infection and

severity of illness associated with speci�c in�uenza viruses may depend on age, geographic area, or genetic factors.

6. Disease severity and pathogenesis measures the severity of illness caused by a particular in�uenza virus in people and/or animals.

7. Antigenic relatedness is a measure of how similar an in�uenza virus not circulating in humans is to seasonal in�uenza vaccines, pre-pandemic candidate vaccine viruses, and stockpiled pre-pandemic vaccines.

The “Ecology and Epidemiology” category contains the �nal risk elements, including:

https://www.cdc.gov/

https://www.cdc.gov/flu/index.htm

https://www.cdc.gov/flu/pandemic-resources/monitoring/irat-virus-summaries.htm

8. Global distribution in animals measures how widespread an in�uenza virus is in animals, the rate of spread over time, and any management factors that may a�ect the distributions.

9. Infections in animals refers to what kinds of animals are impacted by the in�uenza virus and the likelihood of human contact with these animals. For example, are in�uenza infections occurring in wild birds or domestic birds?

10. Human infections refers to evidence and frequency of human infections with an in�uenza virus not currently capable of sustained human-to-human transmission. If evidence exists, under what circumstances are human infections occurring? For example, how frequently and easily does transmission occur after direct and prolonged contact between humans and infected animals?

How are the IRAT’s 10 risk elements ranked and weighted? In�uenza experts generate numerical values (point score) to estimate the pandemic risk associated with each of the 10 risk elements. The point scores fall into three general classi�cations of risk: low risk, moderate risk and high risk.

“low risk” is associated with a point score between 1 and 3;

“moderate risk” is associated with a point score between 4-7; and,

“high risk” is associated with a point score between 8-10.

Each of the 10 risk elements also is weighted according to importance to each of the two questions on “emergence” and “public health impact.”

Potential Emergence Risk (Column 3 in Table)

The �rst question is: “What is the risk that a novel virus has the potential for sustained human-to-human transmission?” The risk elements may be ranked and weighted as follows (with the �rst risk element receiving the highest rank and weight score, and the last risk element receiving the lowest rank and weight score).

Human infections

Transmission in animal models

Receptor binding

Population immunity

Infections in animals

Genomic analysis

Antigenic relatedness

Global distribution in animals

Disease severity and pathogenesis

Antiviral treatment options

Potential Impact Risk (Column 4 in Table)

The second question is: “If the virus were to achieve sustained human-to-human transmission, what is the risk that a novel virus has the potential for signi�cant impact on public health?” The same risk elements could be ranked and weighted as follows (with the �rst risk element receiving the highest rank and weight score, and the last risk element receiving the lowest rank and weight score).

Disease severity and pathogenesis

Population immunity

Human infections

Antiviral treatment options

Antigenic relatedness

Receptor binding

Genomic analysis

Transmission in animal models

Global distribution in animals

Infections in animals

What are the “mean-high” and “mean-low” acceptable score ranges and how are they calculated? Since the IRAT is qualitative in nature, its scores involve some degree of subjectivity. Accordingly, subject matter experts provide a range of “acceptable” scores for each risk element by identifying a lower and upper bound they would consider acceptable from other experts scoring the same element. The mean of the lowest acceptable bound and the mean of the highest acceptable bound from each risk element are used in the weighted “emergence” or “public health impact” calculations to create the “mean-high” and “mean-low” acceptable score ranges.

How often does the IRAT get updated? The IRAT may be updated when new zoonotic or novel in�uenza viruses emerge or undergo a change in characteristics that prompts the need for a new assessment.

What in�uenza viruses have been assessed using the IRAT? CDC has prepared a summary of In�uenza Risk Assessment Tool (IRAT) results.