Digitalization of adverse event management in oncology to improve treatment outcome-A prospective study protocol

Abstract

The occurrence of adverse events frequently accompanies tumor treatments. Side effects should be detected and treated as soon as possible to maintain the best possible treatment outcome. Besides the standard reporting system Common Terminology Criteria for Adverse Events (CTCAE), physicians have recognized the potential of patient-reporting systems. These are based on a more subjective description of current patient reporting symptoms. Patient-reported symptoms are essential to define the impact of a given treatment on the quality of life and the patient's wellbeing. They also act against an underreporting of side effects which are paramount to define the actual value of a treatment for the individual patient. Here, we present a study protocol for a clinical trial that assesses the potential of a smartphone application for CTCAE conform symptom reporting and tracking that is adjusted to the standard clinical reporting system rather than symptom oriented descriptive trial tools. The presented study will be implemented in two parts, both lasting over six months. The first part will assess the feasibility of the application with 30 patients non-randomly divided into three equally-sized age groups (<55years, 55-75years, >75years). In the second part 36 other patients will be randomly assigned to two groups, one reporting using the smartphone and one not. This prospective second part will compare the impact of smartphone reported adverse events regarding applied therapy doses and quality of life to those of patients receiving standard care. We aim for early detection and treatment of adverse events in oncological treatment to improve patients' safety and outcomes. For this purpose, we will capture frequent adverse events of chemotherapies, immunotherapies, or other targeted therapies with our smartphone application. The presented trial is registered at the U.S. National Library of Medicine ClinicalTrials.gov (NCT04493450) on July 30, 2020.

Fig 1. Second part trial design.

Patients who are treated with infusional combination therapy will report their occurred adverse events (symptoms) every two months to physicians. Group 1 will use a smartphone app with standardized answers to report symptoms while it depends on the patients of group 2 which symptoms they report.

Fig 2. Sample size estimation.

Sample size calculation for the Mann-Whitney test given an effect size of d = 1, a type I error rate α = 0.05, a power of 80% led to a required sample size of 36 participants, separated into two groups of 18 individuals each.

Fig 3. NEMO smartphone app.

(a) In the settings, users can choose between two therapy schemes and the corresponding questionnaires as well if they want a reminder to daily answer the questionnaire or whether they prefer to hear possible answers with a male or female voice. (b) If the smartphone app opens, the questionnaire about occurred adverse events can be started by clicking on the plus button. (c,d) Each issue is depicted on an independent site and can be passed by answering the question. An obvious color scheme with high contrast indicates the scoring of the side effect. (e) Information about the current weight or pulse can be entered with a predefined picker to avoid misinterpretation by different scales. (f) Furthermore, patients can enter a comment. (g) At the end of the questionnaire, all given answers are summarized and can be changed if the answer is not correct. (h) If the family doctor adjusts the medication, the physician in the clinic can be informed by pressing the button “medication changed”. The meaning of buttons and settings is explained by short descriptions (e.g. please press the button if there was a general change for medication).

Fig 4. Secure data transfer.

If a patient is willing to transfer its data, a QR code can be generated on the mobile phone (a) that allows secure data transfer via scanning (b). Example of the data transfer from the mobile phone to the desktop computer (image copyright Institute of Medical Systems Biology, Ulm University).

Fig 5. Visualization of transferred adverse events.

The physician in charge can display patients’ transferred data of occurred adverse events as a line plot (a) or heat map (b). This allows a fast and easy analysis.