Increasing interest in individualized treatment strategies for prevention and treatment of health disorders has created a new application domain for dynamic modeling and control. Standard population-level clinical trials, while useful, are not the most suitable vehicle for understanding the dynamics of dosage changes to patient response. A secondary analysis of intensive longitudinal data from a naltrexone intervention for fibromyalgia examined in this dissertation shows the promise of system identification and control. This includes datacentric identification methods such as Model-on-Demand, which are attractive techniques for estimating nonlinear dynamical systems from noisy data. These methods rely on generating a local function approximation using a database of regressors at the current operating point, with this process repeated at every new operating condition. This dissertation examines generating input signals for data-centric system identification by developing a novel framework of geometric distribution of regressors and time-indexed output points, in the finite dimensional space, to generate sufficient support for the estimator. The input signals are generated while imposing “patient-friendly” constraints on the design as a means to operationalize single-subject clinical trials. These optimization-based problem formulations are examined for linear time-invariant systems and block-structured Hammerstein systems, and the results are contrasted with alternative designs based on Weyl's criterion. Numerical solution to the resulting nonconvex optimization problems is proposed through semidefinite programming approaches for polynomial optimization and nonlinear programming methods. It is shown that useful bounds on the objective function can be calculated through relaxation procedures, and that the data-centric formulations are amenable to sparse polynomial optimization. In addition, input design formulations are formulated for achieving a desired output and specified input spectrum. Numerical examples illustrate the benefits of the input signal design formulations including an example of a hypothetical clinical trial using the drug gabapentin. In the final part of the dissertation, the mixed logical dynamical framework for hybrid model predictive control is extended to incorporate a switching time strategy, where decisions are made at some integer multiple of the sample time, and manipulation of only one input at a given sample time among multiple inputs. These are considerations important for clinical use of the algorithm.

Proportional-Integral-Derivative (PID) controllers are a versatile category of controllers that are commonly used in the industry as control systems due to the ease of their implementation and low cost. One problem that continues to intrigue control designers is the matter of finding a good combination of the three parameters - P, I and D of these controllers so that system stability and optimum performance is achieved. Also, a certain amount of robustness to the process is expected from the PID controllers. In the past, many different methods for tuning PID parameters have been developed. Some notable techniques are the Ziegler-Nichols, Cohen-Coon, Astrom methods etc. For all these techniques, a simple limitation remained with the fact that for a particular system, there can be only one set of tuned parameters; i.e. there are no degrees of freedom involved to readjust the parameters for a given system to achieve, for instance, higher bandwidth. Another limitation in most cases is where a controller is designed in continuous time then converted into discrete-time for computer implementation. The drawback of this method is that some robustness due to phase and gain margin is lost in the process. In this work a method of tuning PID controllers using a loop-shaping approach has been developed where the bandwidth of the system can be chosen within an acceptable range. The loop-shaping is done against a Glover-McFarlane type ℋ∞ controller which is widely accepted as a robust control design method. The numerical computations are carried out entirely in discrete-time so there is no loss of robustness due to conversion and approximations near Nyquist frequencies. Some extra degrees of freedom owing to choice of bandwidth and capability of choosing loop-shapes are also involved and are discussed in detail. Finally, comparisons of this method against existing techniques for tuning PID controllers both in continuous and in discrete-time are shown. The results tell us that our design performs well for loop-shapes that are achievable through a PID controller.