Robust C-optimal Design For Estimating Multiple EDps Under The 4-parameter Logistic Model
Abstract
The four-parameter logistic model is often used to describe dose-response functions in many toxicological studies. In this study, under the four-parameter logistic model, optimal designs to estimate the EDp are studied. The EDp is the dose achieving p% of the expected difference between the maximum and the minimum responses. C-optimal design works the best for estimating the EDp, but the best performance is only guaranteed when the goal is for estimating a single EDp. If the c-optimal design for studying a specific EDp is used for studying different EDp values, it may work poorly. This paper shows that the c-optimal design for estimating the EDp truly depends on the value of p under the 4-parameter logistic model. We present a robust c-optimal design that works well for the change in the value of p, so that the design can be used effectively for studying multiple EDp values. In addition, this paper presents a two-stage robust c-optimal design for estimating multiple EDp that is not substantially affected by the mis-specified nominal parameter values.References
A.C. Atkinson, Examples of the Use of an Equivalence Theorem in Constructing Optimum Experimental Designs for Random-Effects Nonlinear Regression Models, Journal of Statistical Planning and Inference. 138 (2008), pp. 2595-2606.
A.C. Atikinson and A.N. Donev, Optimum Experimental Designs, Oxford University Press, London, 1992.
A.C. Atkinson, A.N. Donev, and R.D. Tobias, Optimum experimental designs, with SAS, Oxford University Press, London, 2007.
F. Bretz, H. Dette, and J.C. Pinheirod, Practical Considerations for Optimal Designs in Clinical Dose Finding Studies, Statistic Medicine. 29 (2010), pp. 731-742.
H. Beloeil, M. Eurin, A. Thevenin, D. Benhamou, and J.X. Mazoit, Effective dose of nefopam in 80% of patients (ED80): a study using the continual reassessment method, British Journal of Clinical Pharmacology. 64 (2007), pp. 686-693.
H. Dette, F. Bretz, A. Pepelyshev, and J. Pinheiro, Optimal Designs for Dose-Finding Studies, Journal of the American Statistical Association. 103 (2008), pp. 1225-1237.
V. Dragalin, F. Hsuan, and S.F. Padmanabhan, Adaptive Designs for Dose-finding Studies Based on Sigmoid Emax Model, Journal of Biopharmaceutical Statistics. 17(2007), pp. 1051-1070.
V.V. Fedorov, Theory of Optimal Experiments, Academic Press, 1972.
V.V. Fedorov, and P. Hackl, Model-Oriented Design of Experiments, Springer, New York, 1997.
S.W. Hyun, and W.K. Wong. Yang, Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels, Computational Statistics and Data Analysis. 58 (2013), pp. 276-282.
A. Louie, P. Kaw,W. Liu, N. Jumbe, M.H. Miller, and G.L. Drusano, Pharmacodynamics of Daptomycin in a Murine Thigh Model of Staphylococcus aureus Infection, Antimicrobial Agents and Chemotherapy. 45 (2001), pp. 845-851.
J.M. McGree, J.A. Eccleston, and S.B. Duffull, Compound Optimal Design Criteria for Nonlinear Models, Journal of Biopharmaceutical Statistics. 18 (2008), pp. 646-661.
S.K. Padmanabhan, and V. Dragalin, V. Adaptive Dc-optimal Design for Dose Finding Based on a Continuous Efficacy Endpoint, Biometrical Journal. 52 (2010), pp. 836-852.
F. Pukelsheim, Optimal Design of Experiments, Society for Industrial and Applied Mathematics (SIAM), Philadelphia, PA, 2006.
K. Quinn, The Newton Raphson Algorithm for Function Optimization, unpublished manuscript, University of Washington, 2001.
N. Ting, Dose Finding in Drug Development, Springer, New York, 2006.
P. Tangri, and P. S. R. Lakshmayya, New Drug Development, Approval And Registration Procedures: A Review, International Journalof Institutional Pharmacy and Life Sciences. 2(2) (2012), pp. 2249-6807.
M. Yang, On the de la Garza phenomenon, Ann. Statist. 38 (2010), pp. 2499-2524.
M. Yang, S. Biedermann, and E. Tang, On optimal designs for nonlinear models: a general and efficient algorithm, J Am Stat Assoc.108 (2013), pp. 1411-1420., pp. 1411-1420.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).