Control-Relevant Adaptive Personalized Modeling From Limited Clinical Data for Precise Warfarin Management

Abstract

Warfarin is a challenging drug to administer due to the narrow therapeutic index of the International Normalized Ratio (INR), the inter- and intra-variability of patients, limited clinical data, genetics, and the effects of other medications. Goal: To predict the optimal warfarin dosage in the presence of the aforementioned challenges, we present an adaptive individualized modeling framework based on model (In)validation and semi-blind robust system identification. The model (In)validation technique adapts the identified individualized patient model according to the change in the patient's status to ensure the model's suitability for prediction and controller design. Results: To implement the proposed adaptive modeling framework, the clinical data of warfarin-INR of forty-four patients has been collected at the Robley Rex Veterans Administration Medical Center, Louisville. The proposed algorithm is compared with recursive ARX and ARMAX model identification methods. The results of identified models using one-step-ahead prediction and minimum mean squared analysis (MMSE) show that the proposed framework effectively predicts the warfarin dosage to keep the INR values within the desired range and adapt the individualized patient model to exhibit the true status of the patient throughout treatment. Conclusion: This paper proposes an adaptive personalized patient modeling framework from limited patientspecific clinical data. It is shown by rigorous simulations that the proposed framework can accurately predict a patient's doseresponse characteristics and it can alert the clinician whenever identified models are no longer suitable for prediction and adapt the model to the current status of the patient to reduce the prediction error.

Keywords

• Adaptive modelling
• drug dosing
• model (In)validation
• robust system identification
• warfarin management