Effects of an Ehealth Intervention, SHINE, on Therapy Adherence in Chronic Myeloid Leukemia Patients: A Pretest/ Post-test Intervention Study

Research Article

Phys Med Rehabil Int. 2022; 9(1): 1199.

Effects of an Ehealth Intervention, SHINE, on Therapy Adherence in Chronic Myeloid Leukemia Patients: A Pretest/ Post-test Intervention Study

JAJ (Koos) Ris BBA1,2*, Jeroen JWM Janssen3 and Jacqueline G Hugtenburg2

¹SHINE Health, Voorburg, The Netherlands

²Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands

²Department of Hematology, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands

*Corresponding author: JAJ (Koos) Ris, Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands

Received: May 14, 2022; Accepted: June 18, 2022; Published: June 25, 2022


Background: Chronic myeloid leukemia (CML) is a malignant hematological disorder, which can be effectively treated with tyrosine kinase inhibitors. Nonadherence has been associated with disease progression. To remedy this, an innovative eHealth intervention, SHINE, has been developed: a personalized program built as smart phone application (app). By using the app, CML patients are supported in dealing with everyday life issues.

Aim: This study aimed to investigate the effects of the SHINE app on medication adherence and quality of life (QoL) of CML patients.

Ethics Approval: The studies involving human participants were reviewed and approved by Medisch Ethische Toetsingscommissie (METC) Amsterdam UMC on 21 September 2016, number 2016.405.

Methods: This pre-test/post-test intervention study included CML patients that used during a three-month pre-test period an electronic medicine box (MEMS) and otherwise received usual care. During the three months posttest period the SHINE app was also used. Functionalities of the app include: information presented as a chat, a medication overview, a reminder service. Adherence was measured with MEMS and MARS. Quality of life was measured with EORTC-QLQ-C30.

Results: 14 patients completed the trial out of 67 registered patients. Medication adherence increased after the SHINE app was introduced from 83.4%±18.8% before to 96.9%±4.2% (P< 0.009) measured with MEMS and from 38.5% to 84.6% (P < 0.031) measured with MARS. Quality of life was not influenced.

Conclusion: The SHINE app is a promising medication adherence support tool. Further research is needed to reduce attrition rates and to validate the effects of the intervention on long term medication adherence.

Impact of Findings on Practice:

• This study showed that the innovative electronic smartphone application SHINE in combination with an electronic medication box considerably increased medication adherence in CML patients

• Of the hundreds of apps aiming to improve medication adherence available, less than a dozen apps have a sound evidence base for efficacy. Adding one study, one app to this is significant.


Chronic myeloid leukemia (CML)

CML is a malignant hematological disorder, characterized by a vast accumulation of leukemic white blood cells in blood, bone marrow and spleen. The disease is caused by a reciprocal translocation between the long arms of chromosome 9 and 22, resulting in an abnormally short chromosome 22, known as the Philadelphia chromosome. This translocation juxtaposes the BCR- and the ABL gene, leading to a fusion gene named BCR-ABL. The BCR-ABL fusion protein that is encoded by this abnormality leads to the clinical picture of CML. The disease is fatal if left untreated or when treated inadequately. Treatment with tyrosine kinase inhibitors (TKI) like imatinib, nilotinib or dasatinib however, results in deep molecular remissions in the majority of patients. These patients enjoy a nearnormal life span [1].

Medication non-adherence in CML

Studies indicate that 25-35% of CML patients do not take their medication according to prescription [2]. Patients who take less than 90% of the prescribed dose of imatinib (“optimum adherence level”) have a substantially higher risk of disease progression to more advanced phase and will almost never reach deep molecular remissions that make stopping feasible [3].

Medication non-adherence is a widespread problem [4], with on average 50% of patients not adhering to their therapy, which leads to poorer treatment outcome and higher health care costs [5-11].

More than 200 variables have been identified influencing medication adherence. Reasons for poor adherence may be patientrelated, such as hindering beliefs [12] and personality traits [13]; they may be external [14], such as work-related demands; they may concern the relationship with the health care professional [15]; as well as related to the the regimen prescribed.

Medication non-adherence can be intentional or unintentional [16]. Unintentionally failing to adhere is not the result of a cognitive decision, but of forgetfulness or physical barriers [17]. Intentionally failing to adhere is, if only temporarily, an active, cognitive and explicit decision [18]. For instance, patients report having trouble adhering to their prescription during social activities [19].

Both from the perspective of the patient as well as from a societal perspective, adherence enhancement is urgently needed. However, improving health behavior - including the intake of medicines - is difficult to achieve, both for patients and for health care professionals. Currently, health care professionals try to improve medication adherence among CML patients by improving knowledge through patient education, thereby attempting to convince them that using medication according to the prescription is necessary for their health. They subsequently hope this is enough to improve medication adherence. In reality, the results of this approach are very disappointing [20,21]. Patients are left to solve this by themselves, and solutions for this problem are urgently needed.

To help overcome this problem and with the aim of (1) providing patients with support and (2) providing health care professionals with an effective and efficient tool to support patients, an innovative eHealth intervention called SHINE (not an acronym) was developed. SHINE is a personalized program built as a smartphone application (“app”).

The app was described to patients (“positioned”) as a support tool to deal with everyday issues in the life of a CML patient. The app was connected with an electronic pillbox in order to record medication intake.

The aim of this study was to investigate the effects of the SHINE app on medication adherence of CML patients to their treatment with TKIs and on their overall quality of life.

Methods and Materials

Study Design

A six months pretest-posttest intervention study was performed including patients with CML treated with a TKI in the period September 2018 to July 2019. Over a three-month pretest period patients used an electronic medicine box to monitor medication intake, but received usual care. Subsequently, in a three months posttest phase patients used the SHINE Smartphone application in combination with the electronic medicine box.

Both at the end of the pre-test and the post-test period patients were asked to complete a questionnaire including the Medication Adherence Report Scale (MARS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C 30 (EORTC-QLQ-C30) supplemented with the CML-specific EORTC QLQ-CML24, and several questions on side effects.

The study was approved by the medical ethics committee of the Amsterdam UMC, location VUmc.

The SHINE Intervention

The SHINE intervention is a personalized e-health program aiming to make life for people with CML and using TKI’s easier. It consists of two separate, but connected components: an electronic medicine box (MEMS) and a smartphone app.

The electronic medicine box, battery powered, is connected with the SHINE app through Bluetooth technology. The medicine box records the opening and closing of the lid, which is considered to be equivalent with the intake of a TKI.

Participants could choose between a smaller pill box (15mm x 66mm x 35mm) able to contain three TKI pills and a larger version with a four compartments (22mm x 100mm x 76mm) able to contain a week’s supply of CML medication. Both versions had identical functionality: recording of the medicine intake and connection to the smartphone app.

Through the Bluetooth connection of the he electronic medicine box medicine intake data are transferred to the app. The app contains a multitude of functionalities, amongst which:

• A medication intake overview utilizing the data transferred from the electronic medicine box.

• A chat bot delivering information, tips and tricks on a variety of issues related to life with CML.

• An FAQ section with the information of the prescribed TKI’s standard patient package inserts reshuffled and presented in a novel way. Allowing patients in this way easier access to the information.

• “Smart” reminders, notifications only reminding patients to take their medicines in case they had not done so.

• Other functionalities included options to log side effects and blood values.

• The program was designed to positively approach dealing with all kinds of issues of life with CML. The development process entailed literature research, 10 semi-structured telephone interviews and a questionnaire (n=164), after which the app was created. This process is not the subject of this article.

Patient Recruitment

Patients with CML older than 18 years treated with TKI were selected using the pharmacy information system of the outpatient pharmacy of the Amsterdam UMC, location VUmc. Patients were asked to participate in the study by means of a letter. Patients were also notified to the study by the hematologists of the Amsterdam UMC, location VUmc during consultations and through a news post on the website of the patient advocacy group Hematon. In the letter, during the consultations and on the Hematon website patients were given information on the study and asked to participate in it. Those wishing to participate could register for the study by following a link to a VUmc registration website where they could register for the study. Upon registration patients were asked to submit their email address, give informed consent, provide information about their smartphone and mobile operating system, and were asked which TKI they had been prescribed. They could also choose between the two sizes of available medicine boxes.

CML patients with incompatible smartphones or those who had discontinued TKI treatment were excluded. All others who submitted all information were included.

Participating patients were sent a welcome letter by mail. This letter also contained the chosen electronic medicine box; instructions how to download the app; log in with a unique, personal activation code; and a manual on connecting the electronic medicine box to the smartphone and app. Support by email and by telephone was available.


Adherence was measured using the electronic medicine box, a Medication Event Monitoring System (MEMS) device. Adherence was also measured by means of the questionnaire Medication Adherence Report Scale (MARS-5) [22]. Quality of life was measured with the EORTC-QLQ-C30 [23] aswell aswith EORTC QLQ-CML24 [24], illness perceptions with the Brief IPQ [25] and beliefs about medicines with the BMQ specific [26]. In addition, questions about side effects were asked.

Data Analysis

Medication adherence was calculated as the number of tablets taken divided by the number of prescribed tablets and expressed as a percentage.

An adherence rate of 90% or higher in CML is correlated with a very low chance of disease progression and a much higher chance of attaining deep molecular remission. In the present study “optimal adherence” was introduced, defined as taking at least 90% of the prescribed TKI dose.

A paired sample t-test was used to assess the difference over time in medication adherence as measured with MEMS, expressed as the percentage of prescribed tablets that were consumed. The difference in medication adherence assessed with the MARS questionnaire between the pre- and post-testperiod was analyzed using a McNemar test. Only patients with a MARS-score of 25 were considered to be medication adherent. The change in quality of life score was analyzed with a Wilcoxon signed rank test. Continuous data were checked on normality using QQ-plots. Results were considered to be statistically significant when a p-value was below 0.05. All data was analyzed using SPSS IBM statistics (version 26).



147 patients started the registration for the study. Of these patients, 67 completed the registration and started the pre-test period. Table 1 shows the demographic characteristics of the participating patients and their treatment characteristics. Of the 67 patients who started the pre/test period 12 did not initiate to use the electronic medicine box nor did they download the app. Due to connection problems, the medication adherence data of 28 patients were not properly collected. The remaining 23 entered the post-test phase of the study. Of these, 14 patients completed the study. Figure 1 describes participation and attrition.