Biomedical subjects

M Razzaghi

Publications and source records attributed to M Razzaghi.

6 recordsLinked to original sources

PubMed2000

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.

Air Pollutants, Occupational↗

PubMed1996

On the correlation coefficient between the TD50 and the MTD.

The existence of correlation between the carcinogenic potency and the maximum tolerated dose has been the subject of many investigations in recent years. Several attempts have been made to quantify this correlation in different bioassay experiments. By using some distributional assumptions, Krewski et al. derive an analytic expression for the coefficient of correlation between the carcinogenic potency TD50 and the maximum tolerated dose. Here, we discuss the deviation that may result in using their analytical expression. By taking a more general approach we derive an expression for the correlation coefficient which includes the result of Krewski et al. as a special case, and show that their expression may overestimate the correlation in some instances and yet underestimate the correlation in other instances. The proposed method is illustrated by application to a real dataset.

Animals↗

PubMed1994

Reproducibility of the dose-response curve of steroid-induced cleft palate in mice.

Pregnant CD-1 mice were exposed to cortisone acetate at doses ranging from 20 to 100 mg/kg/day on days 10-13 by oral and intramuscular routes. Multiple replicate assays were conducted under identical conditions to assess the reproducibility of the dose-response curve for cleft palate. The data were fitted to the probit, logistic, multistage or Armitage-Doll, and Weibull dose-response model separately for each route of exposure. The curves were then tested for parallel slopes (probit and logistic models) or coincidence of model parameters (multistage and Weibull models). The 19 replicate experiments had a wide range of slope estimates, wider for the oral than for the intramuscular experiments. For all models and both routes of exposure the null hypothesis of equality of slopes was rejected at a significant level of p < 0.001. For the intramuscular group of replicates, rejection of slope equality could in part be explained by not maintaining a standard dosing regime. The rejection of equivalence of dose-response curves from replicate studies showed that it is difficult to reproduce dose-response data of a single study within the limits defined by the dose-response model. This has important consequences for quantitative risk assessment, public health measures, or development of mechanistic theories which are typically based on a single animal bioassay.

Animals↗

PubMed1993

Developmental toxicity risk assessment: a rough sets approach.

A rough-sets approach was applied to a data set consisting of animal study results and other compound characteristics to generate local and global (certain/possible) sets of rules for prediction of developmental toxicity in human subjects. A modified version of the rough-sets approach is proposed to allow the construction of an approximate set of rules to use for prediction in a manner similar to that of discriminant analysis. The modified rough-sets approach is superior in predictability to the original form of rough-sets methodology. In comparison to discriminant analysis, modified rough sets (approximate rules) appear to be better in overall classification, sensitivity, positive and negative predictive values. The findings were supported by applying the modified rough sets and discriminant analysis on a test data set generated from the original data set by using a resampling plan.

Animals↗

PubMed1992

Process of building biologically based dose-response models for developmental defects.

The problem of developing biologically-based dose-response models is addressed for predicting the prevalence of birth defects at low doses of toxic chemicals administered during pregnancy. To illustrate the process of incorporating biological information, a model is postulated to predict the prevalence of cleft palate for a chemical that reduces embryonic/fetal growth, which results in inadequate palatal cells for closure. Experimental bioassay data examining the prevalence of cleft palate in mice exposed to the herbicide 2,4,5-T are used to illustrate the process. With the limited data available, it is necessary to assume a model for cell growth and the relationship between the cell growth rate parameter and dose of 2,4,5-T. Also, a relationship between cleft palate prevalence and growth is assumed and then checked with experimental data. The purpose of the paper is not to provide a universal biologically based dose-response model for cleft palate, but rather to demonstrate the extent, and type of information and data required. It remains to be seen if the form of the model is appropriate for chemicals that primarily produce embryo/fetal malformations or death via reduced or delayed cellular growth.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1992

On using Lehmann alternatives with nonresponders.

The problem of testing for treatment effect when some subjects in the treatment group may be unaffected by the treatment is considered. A form of the Lehmann alternative suggested by Conover and Salsburg is used that assumes that each control score has the same distribution as the minimum of the known number of responses in the treatment group. It is shown that the locally most powerful test leads to a test statistic that, under the hypothesis of no treatment effect, is the sum of independent pareto random variables whereas under the alternative hypothesis it is the sum of independent random variables from a mixture of two pareto distributions. The limiting distribution of the test statistic under both hypotheses is in the domain of attraction of a stable distribution whose indices are derived. The power of the test is given, and its properties are discussed. A set of data from clinical research involving development of a new drug is used to show application of the procedure and demonstrate its usefulness.

Biometry↗