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    DESIGNS FOR TESTING LACK OF FIT FOR A CLASS OF SIGMOID CURVE MODELS

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    Genre
    Thesis/Dissertation
    Date
    2012
    Author
    Su, Ying
    Advisor
    Raghavarao, Damaraju
    Committee member
    Iglewicz, Boris
    Chitturi, Pallavi
    Chan, Ivan S. F.
    Department
    Statistics
    Subject
    Statistics
    D-optimal Design
    Gompertz Model
    Lack of Fit Test
    Logistic Model
    Nonlinear Design
    Probit Model
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/2476
    
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    DOI
    http://dx.doi.org/10.34944/dspace/2458
    Abstract
    Sigmoid curves have found broad applicability in biological sciences and biopharmaceutical research during the last decades. A well planned experiment design is essential to accurately estimate the parameters of the model. In contrast to a large literature and extensive results on optimal designs for linear models, research on the design for nonlinear, including sigmoid curve, models has not kept pace. Furthermore, most of the work in the optimal design literature for nonlinear models concerns the characterization of minimally supported designs. These minimal, optimal designs are frequently criticized for their inability to check goodness of fit, as there are no additional degrees of freedom for the testing. This design issue can be a serious problem, since checking the model adequacy is of particular importance when the model is selected without complete certainty. To assess for lack of fit, we must add at least one extra distinct design point to the experiment. The goal of this dissertation is to identify optimal or highly efficient designs capable of checking the fit for sigmoid curve models. In this dissertation, we consider some commonly used sigmoid curves, including logistic, probit and Gompertz models with two, three, or four parameters. We use D-optimality as our design criterion. We first consider adding one extra point to the design, and consider five alternative designs and discuss their suitability to test for lack of fit. Then we extend the results to include one more additional point to better understand the compromise among the need of detecting lack of fit, maintaining high efficiency and the practical convenience for the practitioners. We then focus on the two-parameter Gompertz model, which is widely used in fitting growth curves yet less studied in literature, and explore three-point designs for testing lack of fit under various error variance structures. One reason that nonlinear design problems are so challenging is that, with nonlinear models, information matrices and optimal designs depend on the unknown model parameters. We propose a strategy to bypass the obstacle of parameter dependence for the theoretical derivation. This dissertation also successfully characterizes many commonly studied sigmoid curves in a generalized way by imposing unified parameterization conditions, which can be generalized and applied in the studies of other sigmoid curves. We also discuss Gompertz model with different error structures in finding an extra point for testing lack of fit.
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