Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors

Abstract

IMPORTANCE Immune checkpoint inhibitors can produce distinct toxic effects that require prompt recognition and timely management.OBJECTIVE To develop a technology-enabled, dynamically adaptive protocol that can provide the accurate information needed to inform specific remedies for immune toxic effects in patients treated with immune checkpoint inhibitors. DESIGN, SETTING, AND PARTICIPANTSAn open-label cohort study was conducted at a single tertiary referral center from September 6, 2019, to September 3, 2020. The median follow-up duration was 63 (interquartile range, 35.5-122) days. Fifty patients with genitourinary cancers treated with immune checkpoint inhibitors were enrolled.INTERVENTIONS A fit-for-purpose electronic platform was developed to enable active patient and care team participation. A smartphone application downloaded onto patients' personal mobile devices prompted them to report their symptoms at least 3 times per week. The set of symptoms and associated queries were paired with alert thresholds for symptoms requiring clinical action. MAIN OUTCOMES AND MEASURESThe primary end point of this interim analysis was feasibility, as measured by patient and care team adherence, and lack of increase in care team staffing.Operating characteristics were estimated for each symptom alert and used to dynamically adapt the alert thresholds to ensure sensitivity while reducing unnecessary alerts. RESULTSOf the 50 patients enrolled, 47 had at least 1 follow-up visit and were included in the analysis. Median age was 65 years (range, 37-86), 39 patients (83%) were men, and 39 patients (83%) had metastatic cancer, with the most common being urothelial cell carcinoma and renal cell carcinoma (22 [47%] patients each). After initial onboarding, no further care team training or additional care team staffing was required. Patients had a median study adherence rate of 74% (interquartile range, 60%-86%) and 73% of automated alerts were reviewed within 3 days by the clinic team. Symptoms with the highest positive predictive value for adverse events requiring acute intervention included dizziness (21%), nausea/vomiting (26%), and shortness of breath (14%). The symptoms most likely to result in unnecessary alerts were arthralgia and myalgia, fatigue, and cough. CONCLUSIONS AND RELEVANCEThe findings of this cohort study suggest an acceptable and fiscally sound method can be developed to create a dynamic learning system to detect and manage immune-related toxic effects.

Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial

“…Other limitations of this study are that the broad triggers for a telephone triage call (new or worsening symptom) may lead to a significant number of calls that may not always result in meaningful changes to how care is provided. A recent publication by Msaouel et al [ 64 ] has described adaptive and more granular alert thresholds that could prevent and alleviate clinician burden. Clinicians in similar studies have noted the time-consuming nature of ePRO data review, and these broad triggers may compound that burden further and limit clinician compliance to study procedures [ 65 ].…”

Analysis of a Remote Monitoring Program for Symptoms Among Adults With Cancer Receiving Antineoplastic Therapy

“…Further refining thresholds based on their prognostic value might also improve system performance and reduce nursing effort, and this is a subject of ongoing research. 31 Third, patients were followed longitudinally for the duration of their treatment by a centralized team whose function was to respond to their symptom reports. This centralized team could have positively biased the patients’ engagement with the ePROs and might be challenging to implement and scale in resource-constrained institutions.…”

“…Hence, alert thresholds were subjective and potentially variable. Further refining thresholds based on their prognostic value might also improve system performance and reduce nursing effort, and this is a subject of ongoing research . Third, patients were followed longitudinally for the duration of their treatment by a centralized team whose function was to respond to their symptom reports.…”

Characteristics of toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced non-small cell lung cancer: a pooled analysis based on individual patient data of CALGB/Alliance trials

“…Accordingly, careful management of the elderly patients is crucial; for that, established approaches in clinical practice and potential treatments being tested in trials have been well discussed in literatures ( 25 , 26 , 28 ). Promising strategies such as geriatric assessment-driven intervention (GAIN) for chemotherapy ( 29 ), and genomic-adjusted radiation dose (GARD) for radiotherapy ( 30 ) have been tested as effective to reduce toxicity and improve survival, respectively; monitoring based on technology and patient-reported outcomes has been found feasible to detect and treat AEs ( 31 , 32 ).…”