Upper Confidence Limits on Excess Risk for Quantitative Responses

Kodell, Ralph L.; West, R. Webster

doi:10.1111/j.1539-6924.1993.tb01067.x

Cited by 87 publications

(87 citation statements)

References 5 publications

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“…To model a dose-response, R is linked to π i via some monotone function of d. By way of background, it is common in risk assessment to model the probability of an adverse effect (risk) as some core predictor function in dose [4,8,19,21]. Of particular interest is the linear predictor…”

Section: Models and Risk Estimationmentioning

confidence: 99%

Simultaneous confidence bands for Abbott-adjusted quantal response models in benchmark analysis

Buckley

Piegorsch

2008

Statistical Methodology

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We study use of a Scheffé-style simultaneous confidence band as applied to low-dose risk estimation with quantal response data. We consider two formulations for the dose-response risk function, an Abbott-adjusted Weibull model and an Abbott-adjusted log-logistic model. Using the simultaneous construction, we derive methods for estimating upper confidence limits on predicted extra risk and, by inverting the upper bands on risk, lower bounds on the benchmark dose, or BMD, at which a specific level of 'benchmark risk' is attained. Monte Carlo evaluations explore the operating characteristics of the simultaneous limits.

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Section: Models and Risk Estimationmentioning

confidence: 99%

Simultaneous confidence bands for Abbott-adjusted quantal response models in benchmark analysis

Buckley

Piegorsch

2008

Statistical Methodology

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“…In the scope of originally defining the BMD as the dose corresponding to some level of risk for adverse effects (for incidence data), implementation of risk (or probability) based procedures have also been discussed for continuous dose-response information (Gaylor and Slikker, 1990;Kodell and West, 1993;Crump, 1995). Alternatives to such formulations have also been developed where the BMD is estimated from the mean response function (Crump, 1984;Murrell et al, 1998;Slob and Pieters, 1998;Sand et al, 2006).…”

Section: Detailed Review Of the Benchmark Dose Methods Data Formatmentioning

confidence: 98%

The current state of knowledge on the use of the benchmark dose concept in risk assessment

Sand

Victorin

Filipsson

2007

J of Applied Toxicology

102

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This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered.

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“…A formal characterization of exposure risk with single-stimulus continuous data was conceptualized by Gaylor and Slikker (1990) by considering the difference between the response at exposure level x and that at the background level x = 0. Kodell and West (1993) expanded on this seminal concept and defined risk via the function R(…”

Section: Dual-exposure Risk Modeling For Continuous Datamentioning

confidence: 99%

Benchmark dose profiles for joint‐action continuous data in quantitative risk assessment

Deutsch

Piegorsch

2013

Biometrical J

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Benchmark analysis is a widely used tool in biomedical and environmental risk assessment. Therein, estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a prespecified benchmark response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This paper demonstrates how the benchmark modeling paradigm can be expanded from the single-agent setting to joint-action, two-agent studies. Focus is on continuous response outcomes. Extending the single-exposure setting, representations of risk are based on a joint-action dose-response model involving both agents. Based on such a model, the concept of a benchmark profile-a two-dimensional analog of the single-dose BMD at which both agents achieve the specified BMR-is defined for use in quantitative risk characterization and assessment.

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Upper Confidence Limits on Excess Risk for Quantitative Responses

Cited by 87 publications

References 5 publications

Simultaneous confidence bands for Abbott-adjusted quantal response models in benchmark analysis

Simultaneous confidence bands for Abbott-adjusted quantal response models in benchmark analysis

The current state of knowledge on the use of the benchmark dose concept in risk assessment

Benchmark dose profiles for joint‐action continuous data in quantitative risk assessment

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