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