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Quantitative Risk Assessment: Developing a Bayesian Approach to Dichotomous Dose-Response Uncertainty.

ABSTRACT: Model averaging for dichotomous dose-response estimation is preferred to estimate the benchmark dose (BMD) from a single model, but challenges remain regarding implementing these methods for general analyses before model averaging is feasible to use in many risk assessment applications, and there is little work on Bayesian methods that include informative prior information for both the models and the parameters of the constituent models. This article introduces a novel approach that addresses many of the challenges seen while providing a fully Bayesian framework. Furthermore, in contrast to methods that use Monte Carlo Markov Chain, we approximate the posterior density using maximum a posteriori estimation. The approximation allows for an accurate and reproducible estimate while maintaining the speed of maximum likelihood, which is crucial in many applications such as processing massive high throughput data sets. We assess this method by applying it to empirical laboratory dose-response data and measuring the coverage of confidence limits for the BMD. We compare the coverage of this method to that of other approaches using the same set of models. Through the simulation study, the method is shown to be markedly superior to the traditional approach of selecting a single preferred model (e.g., from the U.S. EPA BMD software) for the analysis of dichotomous data and is comparable or superior to the other approaches.

SUBMITTER: Wheeler MW

PROVIDER: S-EPMC7722241 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Quantitative Risk Assessment: Developing a Bayesian Approach to Dichotomous Dose-Response Uncertainty.

Wheeler Matthew W MW Blessinger Todd T Shao Kan K Allen Bruce C BC Olszyk Louis L Davis J Allen JA Gift Jeffrey S JS

Risk analysis : an official publication of the Society for Risk Analysis 20200629 9

Model averaging for dichotomous dose-response estimation is preferred to estimate the benchmark dose (BMD) from a single model, but challenges remain regarding implementing these methods for general analyses before model averaging is feasible to use in many risk assessment applications, and there is little work on Bayesian methods that include informative prior information for both the models and the parameters of the constituent models. This article introduces a novel approach that addresses ma ...[more]

PMID: 32602232

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Project description:Failing to communicate current knowledge limitations, that is, epistemic uncertainty, in environmental risk assessment (ERA) may have severe consequences for decision making. Bayesian networks (BNs) have gained popularity in ERA, primarily because they can combine variables from different models and integrate data and expert judgment. This paper highlights potential gaps in the treatment of uncertainty when using BNs for ERA and proposes a consistent framework (and a set of methods) for treating epistemic uncertainty to help close these gaps. The proposed framework describes the treatment of epistemic uncertainty about the model structure, parameters, expert judgment, data, management scenarios, and the assessment's output. We identify issues related to the differentiation between aleatory and epistemic uncertainty and the importance of communicating both uncertainties associated with the assessment predictions (direct uncertainty) and the strength of knowledge supporting the assessment (indirect uncertainty). Probabilities, intervals, or scenarios are expressions of direct epistemic uncertainty. The type of BN determines the treatment of parameter uncertainty: epistemic, aleatory, or predictive. Epistemic BNs are useful for probabilistic reasoning about states of the world in light of evidence. Aleatory BNs are the most relevant for ERA, but they are not sufficient to treat epistemic uncertainty alone because they do not explicitly express parameter uncertainty. For uncertainty analysis, we recommend embedding an aleatory BN into a model for parameter uncertainty. Bayesian networks do not contain information about uncertainty in the model structure, which requires several models. Statistical models (e.g., hierarchical modeling outside the BNs) are required to consider uncertainties and variability associated with data. We highlight the importance of being open about things one does not know and carefully choosing a method to precisely communicate both direct and indirect uncertainty in ERA. Integr Environ Assess Manag 2021;17:221-232. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Project description:BackgroundMachine learning (ML) predictions are becoming increasingly integrated into medical practice. One commonly used method, ℓ1-penalised logistic regression (LASSO), can estimate patient risk for disease outcomes but is limited by only providing point estimates. Instead, Bayesian logistic LASSO regression (BLLR) models provide distributions for risk predictions, giving clinicians a better understanding of predictive uncertainty, but they are not commonly implemented.MethodsThis study evaluates the predictive performance of different BLLRs compared to standard logistic LASSO regression, using real-world, high-dimensional, structured electronic health record (EHR) data from cancer patients initiating chemotherapy at a comprehensive cancer centre. Multiple BLLR models were compared against a LASSO model using an 80-20 random split using 10-fold cross-validation to predict the risk of acute care utilization (ACU) after starting chemotherapy.FindingsThis study included 8439 patients. The LASSO model predicted ACU with an area under the receiver operating characteristic curve (AUROC) of 0.806 (95% CI: 0.775-0.834). BLLR with a Horseshoe+ prior and a posterior approximated by Metropolis-Hastings sampling showed similar performance: 0.807 (95% CI: 0.780-0.834) and offers the advantage of uncertainty estimation for each prediction. In addition, BLLR could identify predictions too uncertain to be automatically classified. BLLR uncertainties were stratified by different patient subgroups, demonstrating that predictive uncertainties significantly differ across race, cancer type, and stage.InterpretationBLLRs are a promising yet underutilised tool that increases explainability by providing risk estimates while offering a similar level of performance to standard LASSO-based models. Additionally, these models can identify patient subgroups with higher uncertainty, which can augment clinical decision-making.FundingThis work was supported in part by the National Library Of Medicine of the National Institutes of Health under Award Number R01LM013362. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Dataset Information

Quantitative Risk Assessment: Developing a Bayesian Approach to Dichotomous Dose-Response Uncertainty.

Publications

Quantitative Risk Assessment: Developing a Bayesian Approach to Dichotomous Dose-Response Uncertainty.

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