Risk assessment for quantitative responses using a mixture model.
A problem that frequently occurs in biological experiments with laboratory animals is that some subjects are less susceptible to the treatment than others. A mixture model has traditionally been proposed to describe the distribution of responses in treatment groups for such experiments. Using a mixture dose-response model, we derive an upper confidence limit on additional risk, defined as the excess risk over the background risk due to an added dose. Our focus will be on experiments with continuous responses for which risk is the probability of an adverse effect defined as an event that is extremely rare in controls. The asymptotic distribution of the likelihood ratio statistic is used to obtain the upper confidence limit on additional risk. The method can also be used to derive a benchmark dose corresponding to a specified level of increased risk. The EM algorithm is utilized to find the maximum likelihood estimates of model parameters and an extension of the algorithm is proposed to derive the estimates when the model is subject to a specified level of added risk. An example is used to demonstrate the results, and it is shown that by using the mixture model a more accurate measure of added risk is obtained.
Razzaghi
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M
Department of Mathematics, Bloomsburg University, Pennsylvania 17815, USA. razzaghi@bloomu.edu
Kodell
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RL
D000395:Air Pollutants, Occupational / Q000633:toxicity; D000465:Algorithms; D000818:Animals; D000830:Animals, Laboratory; D001699:Biometry / Q000379:methods*; D001786:Blood Glucose / Q000378:metabolism; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D054354:Iron Carbonyl Compounds; D016013:Likelihood Functions; D051379:Mice; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000633:toxicity; D018570:Risk Assessment / Q000379:methods*
D000395:Air Pollutants, Occupational; D001786:Blood Glucose; D009942:Organometallic Compounds; D054354:Iron Carbonyl Compounds