Taking into account variability and uncertainty in exposure - - PowerPoint PPT Presentation

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Taking into account variability and uncertainty in exposure - - PowerPoint PPT Presentation

Taking into account variability and uncertainty in exposure assessment Prise en compte de la variabilit et de l'incertitude sur lvaluation de l'exposition Marie Cornu, Rgis Pouillot, Afssa 1 Exposure assessment "Exposure


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Marie Cornu, Régis Pouillot, Afssa

Taking into account variability and uncertainty in exposure assessment Prise en compte de la variabilité et de l'incertitude sur l’évaluation de l'exposition

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Exposure assessment

"Exposure assessment should provide an estimate with associated uncertainty of the (variability in)

  • ccurrence and level of the pathogen in a specified

portion of a certain food at the time of consumption in a specified population."

European Commission, 2003

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Why should we consider variability and uncertainty?

Fictive examples :

  • Variability
  • « The mean number of Lm per meal is 1… » says the expert

while most individuals eat no Lm and others eat 106 cfu/meal !!!

  • Uncertainty
  • « 1% of individuals eat 102 Lm per meal … » says the expert

while the 1% estimate is not known with precision and may vary from 0.0005% to 10% depending on the assumptions!!!

  • Risk management may differ whether or not variability and uncertainty

are considered

  • this is not a statistician whim
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Variability

Variability represents a true heterogeneity of the population that is a consequence of the physical system and irreducible (but better characterized) by further measurements. Variability between sub-populations

  • Examples: differences in serving sizes between

infants/children/teenagers/adults, male versus female…

  • Variability within a (sub-) population
  • Examples: variability of serving sizes from one person to another,

from one serving (cocktail) to another (main meal)…

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Uncertainty

Uncertainty represents our lack of knowledge and includes :

  • scenario uncertainty

Uncertainty due to necessary selection of processes to model

  • model uncertainty

Uncertainty due to necessary simplification of modelled processes

  • parameter uncertainty

Analytical uncertainty (measurement errors) Sampling uncertainty (too small samples)

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Consumption Contamination

at the time of consumption

Exposure Contamination at t0 (?) Growth model

parameters

Monte Carlo

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Consumption: consumption rates and serving sizes

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Consumption variability

Empirical cumulative distributions of smoked seafood serving sizes (USA population)

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Consumption uncertainty

  • Uncertainty linked to data source
  • National individual dietary survey (e.g. INCA)
  • Reporting errors
  • Purchase database (e.g. Secodip)
  • Aggregated data / home
  • Uncertainty due to survey duration
  • Uncertaintly due to sample size
  • Usually relatively high sample sizes, depends of products:
  • Smoked salmon : 162 days of consumption / 21 000 recorded
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Contamination: Prevalence and level of contamination

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t0?

ÿ t0 = consumption (e.g. Lindqvist & Westöö, 2000)

  • Prevalence
  • Level of contamination at the time of contamination
  • No growth model

ÿ t0 = end of processing or retail (e.g. FDA, 2003)

  • Prevalence
  • Level of contamination at the initial stage (end of processing or retail)
  • Growth model: storage conditions + growth parameters

ÿ t0 = primary production (e.g. Bemrah et al., 1998)

  • Classical "farm-to-fork model" (including all sources of contamination)
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Prevalence

  • Variability :
  • Between sub-categories:
  • Between-farm or between-factory (Miconnet et al., submitted)
  • Between-season variability
  • Between-year variability (general decrease)
  • Variability within a sub-category:
  • Confused with uncertainty
  • Uncertainty:
  • Analytical uncertainty
  • Sensitivity and specificity, reproductibility
  • Sampling uncertainty (low sample sizes)
  • Bayesian approach: Beta priors
  • Frequentist approach: confidence distribution
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2 cold-smoked salmon production sites

Miconnet et al., submitted

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Level of contamination (at t0)

  • Variability :
  • Between sub-categories
  • Usually neglected
  • Variability within a sub-category
  • Use of histograms, distributions…
  • Uncertainty:
  • Analytical uncertainty
  • Censored data (< threshold), repeatability, reproducibility
  • Sampling uncertainty
  • Very low sample sizes
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Growth modelling

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Growth Models

  • Primary model
  • Secondary model

Use in inference: Fitted to growth curves Use in simulation: Predicts the evolution of the population along time Parameters: N0, λ (or lag or or q0), µ (or µmax or d.t.), Nmax (or MPD) Models: modified Gompertz, lag exponential, logistic with delay, Baranyi, … Use in inference: Fitted to observed growth rates (or lag times) Use in simulation: Predicts the effect of environment (temperature, pH, aw…) Parameters: regression meaningless coefficients, or cardinal values Models: polynomial models, cardinal models, gamma models…

van Gerwen & Zwietering, 1998.

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Growth variability?

  • Environmental variability:
  • Variability of time-temperature conditions

ÿDistributions of (t,θ) or of scores (Rosset et al., submitted)

  • Between-product variability

ÿDistribution of µopt or b2 (FDA, 2003) or of (pH, aw…)

  • Within-product variability

ÿOften neglected (confused with uncertainty)

  • L. monocytogenes variability:
  • Between-strain variability

ÿVariability of the growth rate at one temperature (Bergis et al., 2004), and/or cardinal values (Tmin…) (Pouillot et al., 2003)

  • Within-strain variability

ÿOften neglected (confused with uncertainty)

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Growth uncertainty

  • Parameter uncertainty
  • Sampling uncertainty
  • Regression errors
  • Analytical uncertainty
  • Model uncertainty (or variability ?)

ß Primary growth model error ß Secondary growth model error on µ ß Secondary growth model error on λ

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Simulations

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How to model separately V & U:

input parameters

  • Hyperparameters / Embedded distributions

Variability distribution : X ~ Gaussian (Mean, Standard deviation) Uncertainty distribution on its parameters : Mean ~ BetaPert (Min, MP, Max)

  • Probability trees

X ~ BetaPert (min, most probable, max) with a "confidence level" p X ~ Gaussian (mean, standard deviation) with a "confidence level" 1-p

  • Non-parametric Bootstrap

Variability empirical distribution: X ∈ {1, 3, 5, …, 7} Uncertainty distribution of variability distributions: X ∈ {1, 3, 5, …, 7} or {1, 3, 3, …, 7} or {3, 3, 3, …, 7} or {1, 5, 5, …, 7}…

  • Parametric Bootstrap

Similar to non parametric Bootstrap, with a variability parametric distribution

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  • Point estimate of given percentiles
  • Insufficient and statistically incorrect
  • Monte-Carlo
  • Comparison of the model result including “Variability” vs “Variability and

Uncertainty”

  • Second order simulation
  • need to separate variability from uncertainty which may be difficult /

arbitrary

  • Bayesian method
  • The Bayesian framework allows to infer on parameter variability and

uncertainty (using hyperparameters) and to evaluate exposure in a single step

  • but still difficult for complex models

How to model separately V & U:

modelling

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Consumption Contamination

at the time of consumption

Exposure Contamination at t0 (?) Growth model

parameters

Monte Carlo

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2-dimensional Monte Carlo

Uncertain fixed parameters

Simulation MC #1

Uncertain fixed parameters

Simulation MC #2

Uncertain fixed parameters

Simulation MC #1000

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Conclusion

  • Exposure assessment, only a part of a whole risk assessment
  • Integration of variability and uncertainty distributions in a global model
  • Selecting / neglecting variability and uncertainty sources
  • In most published risk assessments, some (or even most) variability

and uncertainty sources are (explicitly or not) neglected

  • Selection of modelled variability and uncertainty distributions, often

leaded by feasibility, and not by sounded sanitary/scientific reasons !

  • Simplifying hypotheses have to be (at least) clearly stated and (as far

as possible) questionned

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Bemrah et al., 1998. Quantitative risk assessment of human listeriosis from consumption of soft cheese made from raw milk. Prev. Vet. Med. 37:129-145 Bergis et al., 2004. Variability of growth of L. monocytogenes in artificially contamainted cold- smoked salmon. Poster in this conference. European commission, 2003. Risk assessment of food borne bacterial pathogens:Quantitative methodology relevant for human exposure assessment. http://europa.eu.int/comm/food/fs/sc/ssc/out308_en.pdf FDA/USDA (2003). Quantitative assessment of relative risk to public health from foodborne L. monocytogenes among selected categories of ready-to-eat foods. http://www.foodsafety.gov/~dms/Lmr2-toc.html Lindqvist & Westöö, 2000. Quantitative risk assessment for L. monocytogenes in smoked or gravad salmon and rainbow trout in Sweden. Int J Food Microbiol 58, 181-96. Miconnet et al., accepted. Uncertainty distribution associated with estimating a proportion in microbial risk assessment Risk Analysis Pouillot et al., 2003. Estimation of uncertainty and variability in bacterial growth using Bayesian

  • inference. Application to L. monocytogenes. Int. J. Food Microbiol. 81:87-104.

Rosset et al., accepted. Time-temperature profiles of chilled ready-to-eat foods in school catering and probabilistic analysis of L. monocytogenes growth. Int. J. Food Microbiol van Gerwen & Zwietering, 1998. Growth and inactivation models to be used in quantitative risk

  • assessments. J Food Prot 61, 1541-9.

References