Methods to Approximate Joint Uncertainty and Variability in Risk

As interest in quantitative analysis of joint uncertainty and interindividual variability (JUV) in risk grows, so does the need for related computational shortcuts. To quantify JUV in risk, Monte Carlo methods typically require nested sampling of JUV in distributed inputs, which is cumbersome and time-consuming. Two approximation methods proposed here allow simpler and more rapid analysis. The first consists of new upper-bound JUV estimators that involve only uncertainty or variability, not both, and so never require nested sampling to calculate. The second is a discrete-probability-calculus procedure that uses only the mean and one upper-tail mean for each input in order to estimate mean and upper-bound risk, which procedure is simpler and more intuitive than similar ones in use. Application of these methods is illustrated in an assessment of cancer risk from residential exposures to chloroform in Kanawah Valley, West Virginia. Because each of the multiple exposure pathways considered in this assessment had separate modeled sources of uncertainty and variability, the assessment illustrates a realistic case where a standard Monte Carlo approach to JUV analysis requires nested sampling. In the illustration, the first proposed method quantified JUV in cancer risk much more efficiently than corresponding nested Monte Carlo calculations. The second proposed method also nearly duplicated JUV-related and other estimates of risk obtained using Monte Carlo methods. Both methods were thus found adequate to obtain basic risk estimates accounting for JUV in a realistically complex risk assessment. These methods make routine JUV analysis more convenient and practical.     

Inventory control under different forms of uncertainty: Ambiguity and stochastic variability

Inventory decision makers routinely face ambiguity due to the psychological awareness that there is unknown information about salient events that is knowable in principle. Researchers on inventory control behavior in the face of uncertainty have primarily focused on uncertainty due to stochastic variability. However, most decision situations in the naturally occurring world involve both forms of uncertainty—ambiguity and stochastic variability. We report the results of two experiments that partial out the effects of ambiguity and stochastic variability by orthogonal manipulation of these two forms of uncertainty in a newsvendor task. Contrary to established mathematical models of decision making under uncertainty, increased ambiguity results in increased mean absolute percentage error, and a corresponding decrease in profit. We also find a systematic bias toward underordering associated with increased ambiguity, which is over and above the bias associated with increased stochastic variability. We do not see evidence for learning with repeated play, so that the effects of induced ambiguity appear to persist. Finally, based on our findings, we suggest measures that managers can use to ameliorate the effects of ambiguity.     

Sensitivity Analysis of a Two‐Dimensional Quantitative Microbiological Risk Assessment: Keeping Variability and Uncertainty Separated

The aim of quantitative microbiological risk assessment is to estimate the risk of illness caused by the presence of a pathogen in a food type, and to study the impact of interventions. Because of inherent variability and uncertainty, risk assessments are generally conducted stochastically, and if possible it is advised to characterize variability separately from uncertainty. Sensitivity analysis allows to indicate to which of the input variables the outcome of a quantitative microbiological risk assessment is most sensitive. Although a number of methods exist to apply sensitivity analysis to a risk assessment with probabilistic input variables (such as contamination, storage temperature, storage duration, etc.), it is challenging to perform sensitivity analysis in the case where a risk assessment includes a separate characterization of variability and uncertainty of input variables. A procedure is proposed that focuses on the relation between risk estimates obtained by Monte Carlo simulation and the location of pseudo‐randomly sampled input variables within the uncertainty and variability distributions. Within this procedure, two methods are used—that is, an ANOVA‐like model and Sobol sensitivity indices—to obtain and compare the impact of variability and of uncertainty of all input variables, and of model uncertainty and scenario uncertainty. As a case study, this methodology is applied to a risk assessment to estimate the risk of contracting listeriosis due to consumption of deli meats.     

Variability and Uncertainty in Swedish Exposure Factors for Use in Quantitative Exposure Assessments

Information of exposure factors used in quantitative risk assessments has previously been compiled and reported for U.S. and European populations. However, due to the advancement of science and knowledge, these reports are in continuous need of updating with new data. Equally important is the change over time of many exposure factors related to both physiological characteristics and human behavior. Body weight, skin surface, time use, and dietary habits are some of the most obvious examples covered here. A wealth of data is available from literature not primarily gathered for the purpose of risk assessment. Here we review a number of key exposure factors and compare these factors between northern Europe—here represented by Sweden—and the United States. Many previous compilations of exposure factor data focus on interindividual variability and variability between sexes and age groups, while uncertainty is mainly dealt with in a qualitative way. In this article variability is assessed along with uncertainty. As estimates of central tendency and interindividual variability, mean, standard deviation, skewness, kurtosis, and multiple percentiles were calculated, while uncertainty was characterized using 95% confidence intervals for these parameters. The presented statistics are appropriate for use in deterministic analyses using point estimates for each input parameter as well as in probabilistic assessments.     

The Effect of Neglecting Correlations When Propagating Uncertainty and Estimating the Population Distribution of Risk

Interest in examining both the uncertainty and variability in environmental health risk assessments has led to increased use of methods for propagating uncertainty. While a variety of approaches have been described, the advent of both powerful personal computers and commercially available simulation software have led to increased use of Monte Carlo simulation. Although most analysts and regulators are encouraged by these developments, some are concerned that Monte Carlo analysis is being applied uncritically. The validity of any analysis is contingent on the validity of the inputs to the analysis. In the propagation of uncertainty or variability, it is essential that the statistical distribution of input variables are properly specified. Furthermore, any dependencies among the input variables must be considered in the analysis. In light of the potential difficulty in specifying dependencies among input variables, it is useful to consider whether there exist rules of thumb as to when correlations can be safely ignored (i.e., when little overall precision is gained by an additional effort to improve upon an estimation of correlation). We make use of well-known error propagation formulas to develop expressions intended to aid the analyst in situations wherein normally and lognormally distributed variables are linearly correlated.     

Variability and Uncertainty Meet Risk Management and Risk Communication

In the past decade, the use of probabilistic risk analysis techniques to quantitatively address variability and uncertainty in risks increased in popularity as recommended by the 1994 National Research Council that wrote Science and Judgment in Risk Assessment. Under the 1996 Food Quality Protection Act, for example, the U.S. EPA supported the development of tools that produce distributions of risk demonstrating the variability and/or uncertainty in the results. This paradigm shift away from the use of point estimates creates new challenges for risk managers, who now struggle with decisions about how to use distributions in decision making. The challenges for risk communication, however, have only been minimally explored. This presentation uses the case studies of variability in the risks of dying on the ground from a crashing airplane and from the deployment of motor vehicle airbags to demonstrate how better characterization of variability and uncertainty in the risk assessment lead to better risk communication. Analogies to food safety and environmental risks are also discussed. This presentation demonstrates that probabilistic risk assessment has an impact on both risk management and risk communication, and highlights remaining research issues associated with using improved sensitivity and uncertainty analyses in risk assessment.     

Probabilistic Framework for the Estimation of the Adult and Child Toxicokinetic Intraspecies Uncertainty Factors

Human health risk assessments use point values to develop risk estimates and thus impart a deterministic character to risk, which, by definition, is a probability phenomenon. The risk estimates are calculated based on individuals and then, using uncertainty factors (UFs), are extrapolated to the population that is characterized by variability. Regulatory agencies have recommended the quantification of the impact of variability in risk assessments through the application of probabilistic methods. In the present study, a framework that deals with the quantitative analysis of uncertainty (U) and variability (V) in target tissue dose in the population was developed by applying probabilistic analysis to physiologically-based toxicokinetic models. The mechanistic parameters that determine kinetics were described with probability density functions (PDFs). Since each PDF depicts the frequency of occurrence of all expected values of each parameter in the population, the combined effects of multiple sources of U/V were accounted for in the estimated distribution of tissue dose in the population, and a unified (adult and child) intraspecies toxicokinetic uncertainty factor UFH-TK was determined. The results show that the proposed framework accounts effectively for U/V in population toxicokinetics. The ratio of the 95th percentile to the 50th percentile of the annual average concentration of the chemical at the target tissue organ (i.e., the UFH-TK) varies with age. The ratio is equivalent to a unified intraspecies toxicokinetic UF, and it is one of the UFs by which the NOAEL can be divided to obtain the RfC/RfD. The 10-fold intraspecies UF is intended to account for uncertainty and variability in toxicokinetics (3.2x) and toxicodynamics (3.2x). This article deals exclusively with toxicokinetic component of UF. The framework provides an alternative to the default methodology and is advantageous in that the evaluation of toxicokinetic variability is based on the distribution of the effective target tissue dose, rather than applied dose. It allows for the replacement of the default adult and children intraspecies UF with toxicokinetic data-derived values and provides accurate chemical-specific estimates for their magnitude. It shows that proper application of probability and toxicokinetic theories can reduce uncertainties when establishing exposure limits for specific compounds and provide better assurance that established limits are adequately protective. It contributes to the development of a probabilistic noncancer risk assessment framework and will ultimately lead to the unification of cancer and noncancer risk assessment methodologies.     

Treatment of Uncertainty in Performance Assessments for Complex Systems

When viewed at a high level, performance assessments (PAs) for complex systems involve two types of uncertainty: stochastic uncertainty, which arises because the system under study can behave in many different ways, and subjective uncertainty, which arises from a lack of knowledge about quantities required within the computational implementation of the PA. Stochastic uncertainty is typically incorporated into a PA with an experimental design based on importance sampling and leads to the final results of the PA being expressed as a complementary cumulative distribution function (CCDF). Subjective uncertainty is usually treated with Monte Carlo techniques and leads to a distribution of CCDFs. This presentation discusses the use of the Kaplan/Garrick ordered triple representation for risk in maintaining a distinction between stochastic and subjective uncertainty in PAs for complex systems. The topics discussed include (1) the definition of scenarios and the calculation of scenario probabilities and consequences, (2) the separation of subjective and stochastic uncertainties, (3) the construction of CCDFs required in comparisons with regulatory standards (e.g., 40 CFR Part 191, Subpart B for the disposal of radioactive waste), and (4) the performance of uncertainty and sensitivity studies. Results obtained in a preliminary PA for the Waste Isolation Pilot Plant, an uncertainty and sensitivity analysis of the MACCS reactor accident consequence analysis model, and the NUREG-1150 probabilistic risk assessments are used for illustration.     

Sensitivity Analysis of a Two-Dimensional Probabilistic Risk Assessment Model Using Analysis of Variance

This article demonstrates application of sensitivity analysis to risk assessment models with two-dimensional probabilistic frameworks that distinguish between variability and uncertainty. A microbial food safety process risk (MFSPR) model is used as a test bed. The process of identifying key controllable inputs and key sources of uncertainty using sensitivity analysis is challenged by typical characteristics of MFSPR models such as nonlinearity, thresholds, interactions, and categorical inputs. Among many available sensitivity analysis methods, analysis of variance (ANOVA) is evaluated in comparison to commonly used methods based on correlation coefficients. In a two-dimensional risk model, the identification of key controllable inputs that can be prioritized with respect to risk management is confounded by uncertainty. However, as shown here, ANOVA provided robust insights regarding controllable inputs most likely to lead to effective risk reduction despite uncertainty. ANOVA appropriately selected the top six important inputs, while correlation-based methods provided misleading insights. Bootstrap simulation is used to quantify uncertainty in ranks of inputs due to sampling error. For the selected sample size, differences in F values of 60% or more were associated with clear differences in rank order between inputs. Sensitivity analysis results identified inputs related to the storage of ground beef servings at home as the most important. Risk management recommendations are suggested in the form of a consumer advisory for better handling and storage practices.     

Hybrid Processing of Stochastic and Subjective Uncertainty Data

Uncertainty analyses typically recognize separate stochastic and subjective sources of uncertainty, but do not systematically combine the two, although a large amount of data used in analyses is partly stochastic and partly subjective. We have developed methodology for mathematically combining stochastic and subjective sources of data uncertainty, based on new "hybrid number" approaches. The methodology can be utilized in conjunction with various traditional techniques, such as PRA (probabilistic risk assessment) and risk analysis decision support. Hybrid numbers have been previously examined as a potential method to represent combinations of stochastic and subjective information, but mathematical processing has been impeded by the requirements inherent in the structure of the numbers, e.g., there was no known way to multiply hybrids. In this paper, we will demonstrate methods for calculating with hybrid numbers that avoid the difficulties. By formulating a hybrid number as a probability distribution that is only fuzzily known, or alternatively as a random distribution of fuzzy numbers, methods are demonstrated for the full suite of arithmetic operations, permitting complex mathematical calculations. It will be shown how information about relative subjectivity (the ratio of subjective to stochastic knowledge about a particular datum) can be incorporated. Techniques are also developed for conveying uncertainty information visually, so that the stochastic and subjective components of the uncertainty, as well as the ratio of knowledge about the two, are readily apparent. The techniques demonstrated have the capability to process uncertainty information for independent, uncorrelated data, and for some types of dependent and correlated data. Example applications are suggested, illustrative problems are shown, and graphical results are given.     

Bayesian Hierarchical Structure for Quantifying Population Variability to Inform Probabilistic Health Risk Assessments

Human variability is a very important factor considered in human health risk assessment for protecting sensitive populations from chemical exposure. Traditionally, to account for this variability, an interhuman uncertainty factor is applied to lower the exposure limit. However, using a fixed uncertainty factor rather than probabilistically accounting for human variability can hardly support probabilistic risk assessment advocated by a number of researchers; new methods are needed to probabilistically quantify human population variability. We propose a Bayesian hierarchical model to quantify variability among different populations. This approach jointly characterizes the distribution of risk at background exposure and the sensitivity of response to exposure, which are commonly represented by model parameters. We demonstrate, through both an application to real data and a simulation study, that using the proposed hierarchical structure adequately characterizes variability across different populations.     

Feasibility Study on the Use of Probabilistic Migration Modeling in Support of Exposure Assessment from Food Contact Materials

The use of probabilistic approaches in exposure assessments of contaminants migrating from food packages is of increasing interest but the lack of concentration or migration data is often referred as a limitation. Data accounting for the variability and uncertainty that can be expected in migration, for example, due to heterogeneity in the packaging system, variation of the temperature along the distribution chain, and different time of consumption of each individual package, are required for probabilistic analysis. The objective of this work was to characterize quantitatively the uncertainty and variability in estimates of migration. A Monte Carlo simulation was applied to a typical solution of the Fick's law with given variability in the input parameters. The analysis was performed based on experimental data of a model system (migration of Irgafos 168 from polyethylene into isooctane) and illustrates how important sources of variability and uncertainty can be identified in order to refine analyses. For long migration times and controlled conditions of temperature the affinity of the migrant to the food can be the major factor determining the variability in the migration values (more than 70% of variance). In situations where both the time of consumption and temperature can vary, these factors can be responsible, respectively, for more than 60% and 20% of the variance in the migration estimates. The approach presented can be used with databases from consumption surveys to yield a true probabilistic estimate of exposure.     

Critical Review and Uncertainty Analysis of Factors Influencing Influenza Transmission

Influenza remains a significant threat to public health, yet there is significant uncertainty about the routes of influenza transmission from an infectious source through the environment to a receptor, and their relative risks. Herein, data pertaining to factors that influence the environmental mediation of influenza transmission are critically reviewed, including: frequency, magnitude and size distribution and virus expiration, inactivation rates, environmental and self‐contact rates, and viral transfer efficiencies during contacts. Where appropriate, two‐stage Monte Carlo uncertainty analysis is used to characterize variability and uncertainty in the reported data. Significant uncertainties are present in most factors, due to: limitations in instrumentation or study realism; lack of documentation of data variability; or lack of study. These analyses, and future experimental work, will improve parameterization of influenza transmission and risk models, facilitating more robust characterization of the magnitude and uncertainty in infection risk.     

Integrating Uncertainty and Interindividual Variability in Environmental Risk Assessment

An integrated, quantitative approach to incorporating both uncertainty and interindividual variability into risk prediction models is described. Individual risk R is treated as a variable distributed in both an uncertainty dimension and a variability dimension, whereas population risk I (the number of additional cases caused by R) is purely uncertain. I is shown to follow a compound Poisson-binomial distribution, which in low-level risk contexts can often be approximated well by a corresponding compound Poisson distribution. The proposed analytic framework is illustrated with an application to cancer risk assessment for a California population exposed to 1,2-dibromo-3-chloropropane from ground water.     

On the Selection of Distributions for Stochastic Variables

One of the main steps in an uncertainty analysis is the selection of appropriate probability distribution functions for all stochastic variables. In this paper, criteria for such selections are reviewed, the most important among them being any a priori knowledge about the nature of a stochastic variable, and the Central Limit Theorem of probability theory applied to sums and products of stochastic variables. In applications of these criteria, it is shown that many of the popular selections, such as the uniform distribution for a poorly known variable, require far more knowledge than is actually available. However, the knowledge available is usually sufficient to make use of other, more appropriate distributions. Next, functions of stochastic variables and the selection of probability distributions for their arguments as well as the use of different methods of error propagation through these functions are discussed. From these evaluations, priorities can be assigned to determine which of the stochastic variables in a function need the most care in selecting the type of distribution and its parameters. Finally, a method is proposed to assist in the assignment of an appropriate distribution which is commensurate with the total information on a particular stochastic variable, and is based on the scientific method. Two examples are given to elucidate the method for cases of little or almost no information.     

Human Salmonellosis: Estimation of Dose-Illness from Outbreak Data

The quantification of the relationship between the amount of microbial organisms ingested and a specific outcome such as infection, illness, or mortality is a key aspect of quantitative risk assessment. A main problem in determining such dose-response models is the availability of appropriate data. Human feeding trials have been criticized because only young healthy volunteers are selected to participate and low doses, as often occurring in real life, are typically not considered. Epidemiological outbreak data are considered to be more valuable, but are more subject to data uncertainty. In this article, we model the dose-illness relationship based on data of 20 Salmonella outbreaks, as discussed by the World Health Organization. In particular, we model the dose-illness relationship using generalized linear mixed models and fractional polynomials of dose. The fractional polynomial models are modified to satisfy the properties of different types of dose-illness models as proposed by Teunis et al . Within these models, differences in host susceptibility (susceptible versus normal population) are modeled as fixed effects whereas differences in serovar type and food matrix are modeled as random effects. In addition, two bootstrap procedures are presented. A first procedure accounts for stochastic variability whereas a second procedure accounts for both stochastic variability and data uncertainty. The analyses indicate that the susceptible population has a higher probability of illness at low dose levels when the combination pathogen-food matrix is extremely virulent and at high dose levels when the combination is less virulent. Furthermore, the analyses suggest that immunity exists in the normal population but not in the susceptible population.     

Evaluating Critical Uncertainty Thresholds in a Spatial Model of Forest Pest Invasion Risk

Pest risk maps can provide useful decision support in invasive species management, but most do not adequately consider the uncertainty associated with predicted risk values. This study explores how increased uncertainty in a risk model's numeric assumptions might affect the resultant risk map. We used a spatial stochastic model, integrating components for entry, establishment, and spread, to estimate the risks of invasion and their variation across a two-dimensional landscape for Sirex noctilio , a nonnative woodwasp recently detected in the United States and Canada. Here, we present a sensitivity analysis of the mapped risk estimates to variation in key model parameters. The tested parameter values were sampled from symmetric uniform distributions defined by a series of nested bounds (±5%, … , ±40%) around the parameters' initial values. The results suggest that the maximum annual spread distance, which governs long-distance dispersal, was by far the most sensitive parameter. At ±15% or larger variability bound increments for this parameter, there were noteworthy shifts in map risk values, but no other parameter had a major effect, even at wider bounds of variation. The methodology presented here is generic and can be used to assess the impact of uncertainties on the stability of pest risk maps as well as to identify geographic areas for which management decisions can be made confidently, regardless of uncertainty.     

Stochastic Judgments in the AHP: The Measurement of Rank Reversal Probabilities

This paper presents a methodology for analyzing Analytic Hierarchy Process (AHP) rankings if the pairwise preference judgments are uncertain (stochastic). If the relative preference statements are represented by judgment intervals, rather than single values, then the rankings resulting from a traditional (deterministic) AHP analysis based on single judgment values may be reversed, and therefore incorrect. In the presence of stochastic judgments, the traditional AHP rankings may be stable or unstable, depending on the nature of the uncertainty. We develop multivariate statistical techniques to obtain both point estimates and confidence intervals of the rank reversal probabilities, and show how simulation experiments can be used as an effective and accurate tool for analyzing the stability of the preference rankings under uncertainty. If the rank reversal probability is low, then the rankings are stable and the decision maker can be confident that the AHP ranking is correct. However, if the likelihood of rank reversal is high, then the decision maker should interpret the AHP rankings cautiously, as there is a subtantial probability that these rankings are incorrect. High rank reversal probabilities indicate a need for exploring alternative problem formulations and methods of analysis. The information about the extent to which the ranking of the alternatives is sensitive to the stochastic nature of the pairwise judgments should be valuable information into the decision-making process, much like variability and confidence intervals are crucial tools for statistical inference. We provide simulation experiments and numerical examples to evaluate our method. Our analysis of rank reversal due to stochastic judgments is not related to previous research on rank reversal that focuses on mathematical properties inherent to the AHP methodology, for instance, the occurrence of rank reversal if a new alternative is added or an existing one is deleted.     

Quantitative Risk Assessment from Farm to Fork and Beyond: A Global Bayesian Approach Concerning Food-Borne Diseases

A novel approach to the quantitative assessment of food-borne risks is proposed. The basic idea is to use Bayesian techniques in two distinct steps: first by constructing a stochastic core model via a Bayesian network based on expert knowledge, and second, using the data available to improve this knowledge. Unlike the Monte Carlo simulation approach as commonly used in quantitative assessment of food-borne risks where data sets are used independently in each module, our consistent procedure incorporates information conveyed by data throughout the chain. It allows "back-calculation" in the food chain model, together with the use of data obtained "downstream" in the food chain. Moreover, the expert knowledge is introduced more simply and consistently than with classical statistical methods. Other advantages of this approach include the clear framework of an iterative learning process, considerable flexibility enabling the use of heterogeneous data, and a justified method to explore the effects of variability and uncertainty. As an illustration, we present an estimation of the probability of contracting a campylobacteriosis as a result of broiler contamination, from the standpoint of quantitative risk assessment. Although the model thus constructed is oversimplified, it clarifies the principles and properties of the method proposed, which demonstrates its ability to deal with quite complex situations and provides a useful basis for further discussions with different experts in the food chain.