AMR Risk Assessment (and Risk Analysis)

Simon Otto, PhD DVM BScAssistant Professor

[email protected]

AMR Risk Assessment(and Risk Analysis)

We acknowledge and pay tribute to the traditional territories of the peoples of Treaty 6, which includes the Cree, Blackfoot, Métis, Nakota Sioux, Iroquois, Dene, Ojibway, Saulteaux, Anishinaabe, Inuit, and many others

whose histories, languages, and cultures continue to influence our vibrant community.

mailto:[email protected]

My Research• One Health epidemiology

of antimicrobial resistance (AMR)

• AMR/antimicrobial use (AMU) surveillance; diagnostic testing

• Antimicrobial stewardship www.heat-amr.com

http://www.heat-amr.com/

Links to Course Learning Outcomes

• Course Learning Outcomes:1. Complex contributing factors to AMU and the

emergence and spread of AMR.4. The role of One Health in complex problems

and AMR.5. AMR surveillance requirements and mitigation

efforts.

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Learning Objectives (Outline)• Objective 1: Explain risk and the components of a Risk

Analysis (Risk Management, Communication and Assessment).

• Objective 2: Explain the process of an AMR Risk Assessment for foodborne pathogens.

• Objective 3: Describe the different types of models and risk assessments.

• Objective 4: Explain the different data sources that can feed into an AMR Risk Assessment.

• Objective 5: Assess why One Health is important for AMR Risk Assessment.

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Risk Analysis

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RISK ASSESSMENT

RISK MANAGEMENT

RISK COMMUNICATION

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Identification of an AMR food safety issue

Develop a risk profile

Rank the food safety issue for risk assessment/management priority

Establish preliminary risk management goals

Establish risk assessment policy and commission a risk assessment

Hazard Identification

Exposure Assessment Hazard Identification

Risk Characterization

Consider the risk assessment results

Implement risk management

decisions

Identify, evaluate, and select risk management

options

Monitor and review risk management measures

Risk

M

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tRi

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Risk

Com

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Surv

eilla

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of A

MR

and

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Immediate/ provisional

decision

No action

Figure 1. Framework for Foodborne AMR Risk Analysis (Codex, CACGL 77-2011 guidelines).

Risk Analysis vs Assessment

• Risk Analysis: three components• Foodborne AMR Risk Assessment:

– “Transparent, science-based approach to identify and assess a chain of events that affect the frequency and amount of AMR microorganisms to which humans are exposed through the consumption of food and to describe the magnitude and severity of the adverse [human] health effects from that exposure.”

The process of combining evidence to provide an estimate of risk and evaluate interventions

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FAO – Food Safety Risk AnalysisGuide

• Supplemental, broad reference for Food Safety Risk Analysis– 2007 FAO Food Safety Risk Assessment

guidelines– (The framework used by Codex)

http://www.fao.org/3/a0822e/a0822e.pdf

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http://www.fao.org/3/a0822e/a0822e.pdf

Two Components of Risk?

1. Probability?

2. Severity?

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Risk Analysis• Risk is function of the:

1. Probability/likelihood of an adverse health event• e.g. prevalence of the foodborne hazard in the

food

+2. Severity of that event should it occur

• e.g. severity of the exposure to the hazard assuming it is in the food

• hazard and host factors

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Video for your info: https://www.youtube.com/watch?v=PZmNZi8bon8

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https://www.youtube.com/watch?v=PZmNZi8bon8

Analysis of Complex Systems

• Use of a “model” to represent the analysis of a complex system– What are the main characteristics?

• Iterative, evolving, integrated, dynamic– Parameters incorporate uncertainty into the

process (probabilistic vs deterministic)– Model allows for incorporation/integration of

diverse but related sub-systems

Javier Sanchez, UPEI, 2016

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Risk Analysis for Managing and Regulating Risks

• Regulation is a mechanism to control risk– Risk Management option (manufacturing,

processing, commercialization)– But they impose a societal cost and (ideally)

should be consistent with their risk reduction potential

– Risk Analysis provides tools to quantify the amount of risk reduction for each measure

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Risk Analysis

• Tool intended to provide decision-makers with an objective, repeatable and documented assessment of the risks posed by a particular course of action– What can go wrong?– How likely is it to go wrong?– Consequences?– What can be done?

Javier Sanchez, UPEI, 2016

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Risk Management• Weighing policy alternatives in consultation

with stakeholders• Consider the risk assessment and other

factors for consumer protection and promotion of fair trade

• Select optimal prevention and control methods to manage hazards and reduce risk

• Review the outcome• Goal: to protect public health

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Risk Analysis Frameworks

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Uncertainty and Variability

• Uncertainty: lack of data or incomplete understanding of data– Reduce with further measurement/study

• Variability: inherent heterogeneity in the data– Effect of chance; function of the system– Cannot reduce with more measurement– Reduce by changing the system

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Goals of AMR Risk Assessment

• Vary with objectives set by risk manager– Estimate of risks to human health from AMR

attributable to AMU in animals– Identify and incorporate uncertainty into risk

estimation and identify gaps in science– Investigate the consequence to animal health

and impacts of control strategies on the risk to public health

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Snary + McEwen, Ch. 3 AMR Risk Assessment, IN Guardabassi, Jensen, Kruse, “Guide to AMU in Animals”, 2008.

Top-down vs Bottom-up• Bottom-up:Source farm-to-fork consumption outcomes• Adv: can evaluate risk management options• Disadv:

– Intensive (data, time, skills)– Data gaps uncertainty – may (not) be fixed

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Top-down vs Bottom-up• Top-down:

# human cases % attributable to source of interest– Notifiable diseases, epi studies

• Adv: simple (good and bad)• Disadv: biased data, attribution to specific

food source/animal, subjectivity– Cannot evaluate risk management options

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decisions


options


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decision

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Figure 1. Framework for Foodborne AMR Risk Analysis (Codex, CAC/GL 77-2011 guidelines).

http://www.fao.org/input/download/standards/11776/CXG_077e.pdf

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decisions


options


Risk

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Risk

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decision

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decisions


options


Risk

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inar

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k m

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Risk

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mun

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of A

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decision

No action


Codex, CAC/GL 63-2007



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decisions


options


Risk

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inar

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k m

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Risk

Com

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decisions


options


Risk

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skAs

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inar

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Risk

Com

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eilla

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of A

MR

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of i

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PROVISIONALdecision

No action



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decisions


options


Risk

M

anag

emen

tRi

skAs

sess

men

tPr

elim

inar

y ris

k m

anag

emen

t ac

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es

Risk

Com

mun

icat

ion

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eilla

nce

of A

MR

and

othe

r sou

rces

of i

nfor

mat

ion


decision

No action



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decisions


options


Risk

M

anag

emen

tRi

skAs

sess

men

tPr

elim

inar

y ris

k m

anag

emen

t ac

tiviti

es

Risk

Com

mun

icat

ion

Surv

eilla

nce

of A

MR

and

othe

r sou

rces

of i

nfor

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ion


decision

No action



Risk Assessment Policy

• What is the risk question?• Do’s

– Ensures the risk assessment is:• Systematic• Complete• Unbiased• Transparent

– Clear mandate from risk manager to address:• Scope? address uncertainty? Assumptions?

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Risk Assessment Policy

• Don’ts– Lack of transparency– Lack of clarity of scope or risk management

options– Scope creep– Ignores uncertainty– Does not state assumptions

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Commission a Risk Assessment

• Risk manager wants an evaluation of relevant scientific knowledge about an identified risk

• Goal:– To make an informed decision regarding

appropriate risk management activities

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Type of Model?

• Qualitative (low, medium, high)• Semi-quantitative (risk ranking)• Quantitative – mathematical models

– Most common today– Based in quantitative microbial risk

assessment (QMRA)• Accounts for population dynamics of the organism• What about AMR genes? See later

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Subjectivity?

Stochastic vs Deterministic

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• Describe the foodborne AMR hazard• Literature and surveillance data

– Specific strains/genotypes of organism– Combination of organism with food product– AMR determinants (genes, plasmids)– Antimicrobial agents– Biology and niche-dependent differences

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AMU selecting for AMR*

Animal/crop and microbial factors affecting dissemination of AMR*

Other sources of AMR* for target animal/crop

Frequency/ concentration of AMR* at slaughter/ harvest

Consumer factors: freq/ conc at food consumption

Microbial factors: transfer and maintenance of AMR

Food processing factors: freq/conc of organism

Sele

ctio

n an

d di

ssem

inat

ion

of A

MR*

Expo

sure

to A

MR

from

con

sum

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Foo

d

Objective: estimate magnitude of human exposure to AMR* considering all relevant pathways/risk factors. AMR* = AMR

organisms or genes

ExposureAssessment

Figu

re 2

a. F

ram

ewor

k fo

r Foo

dbor

ne A

MR

Risk

An

alys

is (C

odex

, CAC

/GL

77-2

011

guid

elin

es).


Exposure Assessment• Fundamental activities:

– Clear description of exposure pathway– Necessary data requirements– Summarise the data

• Factors to consider:– Pre-harvest factors (e.g., AMU frequency/

effect)– Processing factors– AMR gene transmission?

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Qualitative description

↑ treatment failures/ loss of treatment options

↑ severity of infection/ disease(prolonged disease, ↑ hospitalizations, ↑ mortality)

↑ frequency of infection/disease

Dis

ease

rela

ted

to p

atho

gens

Adve

rse

heal

th e

ffect

s rel

ated

to A

MR

Objective: estimate of the adverse health effects related to AMR conditional on infection and disease with an AMR organism or AMR gene.

Hazard Characterization

Figu

re 2

b. F

ram

ewor

k fo

r Foo

dbor

ne A

MR

Risk

An

alys

is (C

odex

, CAC

/GL

77-2

011

guid

elin

es).

Semi-quantitative models

Quantitative models

Options to translate exposure to AMR into probability of

infection and disease

Estimates of the further outcomes that can occur as a result of disease due to

AMR pathogens



• Translate the levels of exposure to likelihood of an array of adverse health events/outcomes– Determination of risk factors (for the hazard)– Defining the site/mechanism of action– Measuring the does-response relationship

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• Risk outcome = disease from infection– Difference: specific focus on AMR organism– Complications from treatment failure or

increased severity attributable to AMR• May be informed by info from non-AMR

organisms– Lack of data for AMR organisms– Lack of methods for AMR organisms

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Dose-Response Models

• Develop relationship between level of microbial exposure and likelihood of occurrence of adverse event

• Challenges:– We don’t have experimental data for many

foodborne pathogens in humans– We don’t have AMR-specific data

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What about AMR C. jejuni?

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• Uses stochastic simple death processes and Markov chains to calculate total risk from exposure to susceptible and resistantpathogens based on original DRM


• Form and outputs vary depending on risk management request (RA Policy)– Risk estimate– Evaluation of Risk Management Options– Characterize uncertainty/variability– Data gaps

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Exposure Assessment


Risk Estimate


• Other elements to consider:– Sensitive sub-populations– Key assumptions and impact on validity– Explicit explanation of variability/uncertainty– Sensitivity and uncertainty analysis– Strengths/weaknesses and limitations– Alternatives to be considered– Key conclusions

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Foodborne AMR Risk Management Options

• See Table 1 in Codex CAC/GL 77-2011 for more complete discussion

• Pre-harvest options– Animal feed, animal management (drug use),

crop production, waste management• Post-harvest options

– Prevent food contamination, microbial criteria

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Another Resource

• USFDA: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-152-evaluating-safety-antimicrobial-new-animal-drugs-regard-their-microbiological-effects

• Uses the OIE framework

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https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-152-evaluating-safety-antimicrobial-new-animal-drugs-regard-their-microbiological-effects

Some examples:

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https://doi.org/10.1016/j.ijfoodmicro.2020.108559

https://doi.org/10.1016/j.ijfoodmicro.2020.108559

Some examples:

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https://doi.org/10.1111/j.1539-6924.2006.00723.x

https://doi.org/10.1111/j.1539-6924.2006.00723.x

Some examples:

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https://doi.org/10.1089/fpd.2010.0550

https://doi.org/10.1089/fpd.2010.0550

Some examples:• USFDA, CVM, Vose D et al., 2000. Human Health

Impact of Fluoroquinolone Resistant CampylobacterAttributed to the Consumption of Chicken (https://www.fda.gov/media/76429/download)

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https://doi.org/10.1093/cid/ciu496

https://www.fda.gov/media/76429/download

https://doi.org/10.1093/cid/ciu496

Important Considerations

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https://doi.org/10.3389/fmicb.2019.01107

https://doi.org/10.3389/fmicb.2019.01107

Risk Communication• Happens throughout the risk analysis process

– Risk related factors– Risk perceptions

• Between/among:– Risk assessors– Risk managers– Consumers– Industry– Academia– Other stakeholders

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What is Risk Communication?

• Objective: create an informative and motivational dialogue about the nature and mitigation of a risk– Forestall a crisis– Lessen its impact

Cole & Fellows, Southern Communication Journal, 2008, 73:3, https://doi.org/10.1080/10417940802219702

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https://doi.org/10.1080/10417940802219702

Risk Communication

https://www.youtube.com/watch?v=3lHGshTDMCw 55

https://www.youtube.com/watch?v=3lHGshTDMCw

Why is risk communication so important? (and not just about science)

https://www.youtube.com/watch?v=cm0b3mknhAE – apologies for language! 56

https://www.youtube.com/watch?v=cm0b3mknhAE

Summary• Risk and Risk Analysis

– Risk Management, Assessment and Communication

• Process of AMR Risk Assessment• Types of models, top-down vs bottom-up• Data sources for risk assessment• One Health considerations

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Thank you!

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Discussion Question

1. What are the possible information sources for identification of AMR food safety issue and to inform an AMR risk assessment?

2. Why is it important to use a One Health lens for data sources for AMR Risk Assessment?

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AMR Risk Assessment (and Risk Analysis)

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