Abstract

http://ssrn.com/abstract=943283
 
 

References (20)



 


 



Comparing Experimental Designs for Benchmark Dose Calculations for Continuous Endpoints


Kristi Kuljus


affiliation not provided to SSRN

Dietrich Von Rosen


affiliation not provided to SSRN

Salomon Sand


affiliation not provided to SSRN

Katarina Victorin


affiliation not provided to SSRN


Risk Analysis, Vol. 26, Issue 4, pp. 1031-1043, August 2006

Abstract:     
The BMD (benchmark dose) method that is used in risk assessment of chemical compounds was introduced by Crump (1984) and is based on dose-response modeling. To take uncertainty in the data and model fitting into account, the lower confidence bound of the BMD estimate (BMDL) is suggested to be used as a point of departure in health risk assessments. In this article, we study how to design optimum experiments for applying the BMD method for continuous data. We exemplify our approach by considering the class of Hill models. The main aim is to study whether an increased number of dose groups and at the same time a decreased number of animals in each dose group improves conditions for estimating the benchmark dose. Since Hill models are nonlinear, the optimum design depends on the values of the unknown parameters. That is why we consider Bayesian designs and assume that the parameter vector has a prior distribution. A natural design criterion is to minimize the expected variance of the BMD estimator. We present an example where we calculate the value of the design criterion for several designs and try to find out how the number of dose groups, the number of animals in the dose groups, and the choice of doses affects this value for different Hill curves. It follows from our calculations that to avoid the risk of unfavorable dose placements, it is good to use designs with more than four dose groups. We can also conclude that any additional information about the expected dose-response curve, e.g., information obtained from studies made in the past, should be taken into account when planning a study because it can improve the design.

Number of Pages in PDF File: 13

Accepted Paper Series





Date posted: November 7, 2006  

Suggested Citation

Kuljus, Kristi and von Rosen, Dietrich and Sand, Salomon and Victorin, Katarina, Comparing Experimental Designs for Benchmark Dose Calculations for Continuous Endpoints. Risk Analysis, Vol. 26, Issue 4, pp. 1031-1043, August 2006. Available at SSRN: http://ssrn.com/abstract=943283 or http://dx.doi.org/10.1111/j.1539-6924.2006.00798.x

Contact Information

Kristi Kuljus (Contact Author)
affiliation not provided to SSRN
No Address Available
Dietrich Von Rosen
affiliation not provided to SSRN
No Address Available
Salomon Sand
affiliation not provided to SSRN
No Address Available
Katarina Victorin
affiliation not provided to SSRN
No Address Available
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References:  20

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