Towards an early warning system for monitoring of cancer patients using hybrid interactive machine learning.

Background: The use of smartphone apps in cancer patients undergoing systemic treatment can promote the early detection of symptoms and therapy side effects and may be supported by machine learning (ML) for timely adaptation of therapies and reduction of adverse events and unplanned admissions.

Objective: We aimed to create an Early Warning System (EWS) to predict situations where supportive interventions become necessary to prevent unplanned visits. For this, dynamically collected standardized electronic patient reported outcome (ePRO) data were analyzed in context with the patient's individual journey. Information on well-being, vital parameters, medication, and free text were also considered for establishing a hybrid ML model. The goal was to integrate both the strengths of ML in sifting through large amounts of data and the long-standing experience of human experts. Given the limitations of highly imbalanced datasets (where only very few adverse events are present) and the limitations of humans in overseeing all possible cause of such events, we hypothesize that it should be possible to combine both in order to partially overcome these limitations.

Methods: The prediction of unplanned visits was achieved by employing a white-box ML algorithm (i.e., rule learner), which learned rules from patient data (i.e., ePROs, vital parameters, free text) that were captured via a medical device smartphone app. Those rules indicated situations where patients experienced unplanned visits and, hence, were captured as alert triggers in the EWS. Each rule was evaluated based on a cost matrix, where false negatives (FNs) have higher costs than false positives (FPs, i.e., false alarms). Rules were then ranked according to the costs and priority was given to the least expensive ones. Finally, the rules with higher priority were reviewed by two oncological experts for plausibility check and for extending them with additional conditions. This hybrid approach comprised the application of a sensitive ML algorithm producing several potentially unreliable, but fully human-interpretable and -modifiable rules, which could then be adjusted by human experts.

Results: From a cohort of 214 patients and more than 16'000 available data entries, the machine-learned rule set achieved a recall of 19% on the entire dataset and a precision of 5%. We compared this performance to a set of conditions that a human expert had defined to predict adverse events. This "human baseline" did not discover any of the adverse events recorded in our dataset, i.e., it came with a recall and precision of 0%. Despite more plentiful results were expected by our machine learning approach, the involved medical experts a) had understood and were able to make sense of the rules and b) felt capable to suggest modification to the rules, some of which could potentially increase their precision. Suggested modifications of rules included e.g., adding or tightening certain conditions to make them less sensitive or changing the rule consequences: sometimes further monitoring the situation, applying certain test (such as a CRP test) or applying some simple pain-relieving measures was deemed sufficient, making a costly consultation with the physician unnecessary. We can thus conclude that it is possible to apply machine learning as an inspirational tool that can help human experts to formulate rules for an EWS. While humans seem to lack the ability to define such rules without such support, they are capable of modifying the rules to increase their precision and generalizability.

Conclusions: Learning rules from dynamic ePRO datasets may be used to assist human experts in establishing an early warning system for cancer patients in outpatient settings.