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.

There is increasing interest in the medical and behavioral health communities towards developing effective strategies for the treatment of chronic diseases. Among these lie adaptive interventions, which consider adjusting treatment dosages over time based on participant response. Control engineering offers a broad-based solution framework for optimizing the effectiveness of such interventions. In this thesis, an approach is proposed to develop dynamical models and subsequently, hybrid model predictive control schemes for assigning optimal dosages of naltrexone, an opioid antagonist, as treatment for a chronic pain condition known as fibromyalgia. System identification techniques are employed to model the dynamics from the daily diary reports completed by participants of a blind naltrexone intervention trial. These self-reports include assessments of outcomes of interest (e.g., general pain symptoms, sleep quality) and additional external variables (disturbances) that affect these outcomes (e.g., stress, anxiety, and mood). Using prediction-error methods, a multi-input model describing the effect of drug, placebo and other disturbances on outcomes of interest is developed. This discrete time model is approximated by a continuous second order model with zero, which was found to be adequate to capture the dynamics of this intervention. Data from 40 participants in two clinical trials were analyzed and participants were classified as responders and non-responders based on the models obtained from system identification. The dynamical models can be used by a model predictive controller for automated dosage selection of naltrexone using feedback/feedforward control actions in the presence of external disturbances. The clinical requirement for categorical (i.e., discrete-valued) drug dosage levels creates a need for hybrid model predictive control (HMPC). The controller features a multiple degree-of-freedom formulation that enables the user to adjust the speed of setpoint tracking, measured disturbance rejection and unmeasured disturbance rejection independently in the closed loop system. The nominal and robust performance of the proposed control scheme is examined via simulation using system identification models from a representative participant in the naltrexone intervention trial. The controller evaluation described in this thesis gives credibility to the promise and applicability of control engineering principles for optimizing adaptive interventions.