Rogers, James R.

AbstractWith a view to finding new applications of biomedical system dynamics, this article expands upon on our talk at the 2021 International System Dynamics Conference on the occasion of receiving the J. W. Forrester Award for the article, “Personalized ESA doses for anemia management in hemodialysis patients with end‐stage renal disease” (System Dynamics Review 2018, 34(1–2): 121–153). We summarize the evolution of a project which took place in a clinical setting between 2008 and 2015 that led to the award‐winning article. We present concepts from receptor theory that informed the first system dynamics application of biophysical system dynamics to the successful diagnosis, prescription, administration, and improvement of individualized patient care. We expand upon these ideas to present a generalized structure, DART (Dynamic Approach to Receptor Theory). It can be used to simulate the physiological effects of any agent, be it an exogenous pharmacological agent, an endogenous enzyme or hormone, or a toxin of some sort. We suggest including within the pharmacological technical literature easily acquired but frequently omitted critical parameter values and rate constants. These would enable researchers to perform transient analyses of biophysical phenomena in addition to static equilibrium analyses typically performed. With the availability of this data, we suggest that the fundamental tools of system dynamics might be used to reconceptualize the 100‐year‐old field of “occupation theory” (today, receptor theory) to deliver high‐resolution insights into physiological dynamics and the preventive, prescriptive, and palliative interventions they might require. It is our hope that these ideas could pave the way forward to novel, groundbreaking applications in biomedical system dynamics. © 2022 System Dynamics Society.

AbstractEnd‐stage renal disease (ESRD) patients receiving hemodialysis are typically anemic due to a lack of erythropoietin (EPO), a hormone required for red blood cell (RBC) production. EPO replacement therapy is complex, often resulting in oscillating hemoglobin (Hb) levels. EPO dosing protocols do not account for endogenous delays and appear to contribute to, if not cause, Hb variability. The Mayo Clinic Anemia Management System (MCAMS) is based on a physiological simulation of the production and lifespan of RBCs, driven by EPO dosage schedules. Patient‐specific parameters were found such that simulated Hb levels matched historical Hb levels in response to historical EPO doses. The calibrated model was used to identify new dosing regimens that stabilize Hb. MCAMS has been used to recommend individualized EPO dosage regimens to maintain stable Hb levels within a desired target range for more than 600 patients, improving patient outcomes while reducing medication costs by about 40 percent.© 2018 System Dynamics Society