Ascertaining Medication Use and Patient-Reported Outcomes via an App and Exploring Gamification in Patients With Multiple Sclerosis Treated With Interferon β-1b: Observational Study

Abstract

Background The BETACONNECT autoinjector and myBETAapp app were designed to support patients with multiple sclerosis receiving interferon β-1b and are an ideal platform for digital observational studies. A recent pilot study in Germany demonstrated the feasibility of using the app to recruit patients, obtain informed consent, and evaluate medication-taking behavior over 6 months. Objective This study aims to describe medication-taking behavior for 1 year in patients with multiple sclerosis receiving interferon β-1b based on data collected from the app and to provide information on patient-reported outcomes (PROs). The optional use of the cognitive training tool PEAK (Peak, formerly Brainbow Ltd) is included to test the feasibility of gamification in this setting. Methods A prospective and retrospective, exploratory, digital, observational cohort study was conducted among users of the app in Germany. Invitations to participate were sent to patients’ apps between February and May 2019. Participants provided electronic informed consent. Injection-related data from consenting patients’ devices were collected prospectively for 1 year following the consent date and retrospectively for ≤1 year from the first day of use (if historical data were available). Participants also completed three electronic PRO instruments every 3 months: the EuroQol 5-Dimension, 5-Level questionnaire (EQ-5D-5L); the Treatment Satisfaction Questionnaire for Medication (TSQM; version II); and a questionnaire on satisfaction with treatment support (on a server accessed via an emailed hyperlink). All patients were offered optional access to the professional version of PEAK. Results Of 1778 registered app accounts (May 2019), 79 patients (4.44%) provided informed consent; 62 (3.49%) were eligible for inclusion in the prospective analysis, of whom, 60 (97%) also had retrospective data. The mean age of the 62 participants was 43.2 (SD 11.5) years and 41 (66%) were women. Compliance over the 1-year prospective observational period (primary end point) was high (median 98.9%, IQR 94.3%-100%) and similar among men and women. Persistence and adherence (coprimary end points) decreased from 85% (53/62) and 74% (46/62), respectively, at 6 months to 76% (47/62) and 65% (40/62), respectively, at 12 months; both were higher in men than in women. A retrospective analysis showed similar patterns. The PRO questionnaires were answered by 79% (49/62) of the participants at baseline and 50% (31/62) of them at month 12. Women had more severe problems in some EQ-5D-5L dimensions (mobility, usual activities, and pain/discomfort) and lower median convenience scores on the TSQM (version II) than men. At month 12, 84% (26/31) of the patients were satisfied or very satisfied with the app. PEAK was used by 67% (14/21) of men and 49% (20/41) of women. Conclusions This study showed high compliance and decreasing persistence and adherence over 1 year and demonstrated the feasibility of including remotely completed electronic PRO instruments in digital observational studies.

Barriers and facilitators for recruiting and retaining male participants into longitudinal health research: a systematic review

“…The oldest of these studies was published from 1976 [ 36 ] and the most recent, 2023 [ 37 , 38 ]. All of the included studies were conducted in Western countries except Cheraghi et al, which was based in the Middle East [ 39 ] and Schilling et al, which was based in India [ 37 ]; two were located in United Kingdom [ 40 , 41 ], two in France [ 42 , 43 ], one in Finland [ 44 ], one in Sweden [ 45 ], one in The Netherlands [ 46 ], one study across combined European nations [ 29 ], one in Germany [ 47 ] ten in North America [ 36 , 48 – 56 ] and three in Australia [ 38 , 57 , 58 ] and are described in Table 1 . Participant characteristics varied with study focus including participants with specific health conditions, such as overweight [ 41 , 57 ], having an occupational injury [ 40 , 41 ], having visited a sexually transmitted infection clinic [ 46 ], or being treated for a psychological disorder [ 44 , 50 , 53 ], COVID related issues [ 37 , 54 ], or habits such as alcohol abuse and smoking [ 56 ].…”

“…The questionnaires used cover a broad range of topics, such as living conditions, family situation, health, health behaviours, and financial resources Lee et al 2009 [ 61 ] The European Male Ageing Study (EMAS) European cities: Florence (Italy), Leuven (Belgium), Lodz (Poland), Malmo ¨ (Sweden), Manchester (United Kingdom), Santiago de Compostela (Spain), Szeged (Hungary) and Tartu (Estonia) Examine aspects of aging in men Prospective cohort study Aging Questionnaire: assess quality of life, depressive symptoms, Adverse Life Events Scale, Physical Activity Scale, International Prostate Symptom Score, previous surgical procedures, sexual function questionnaire. Screening: Physical and cognitive performance, Anthropometry, Calcaneal ultrasound, Food diary, blood samples Limmroth et al 2023 [ 47 ] PROmyBETAappGame Multiple Locations, Germany a Investigate medication-taking behaviour in patients with multiple sclerosis receiving interferon β-1b for 1 year and to provide additional information on patient reported outcomes. To test the feasibility of gamification (using cognitive training tool PEAK) to incentivise patients to remain committee to the study Prospective and retrospective, noninterventional observational cohort study Multiple sclerosis Demographic data: age gender, injection-related data: date/time of injection, injection speed and injection depth (collected from the app or manually recorded), self-reported measures: health-related quality of life, EuroQol-5-Dimension 5-Level questionnaire, Treatment Satisfaction Questionnaire of Medication, questionnaire on satisfaction with the BETAPLUS, BETACONNECT and the app via a service questionnaire Markanday et al 2013 [ 58 ] Geelong Osteoporosis Study Geelong, Australia Investigate sex-differences in non-participation at baseline of the Geelong Osteoporosis Study (GOS) Prospective cohort study Osteoporosis Reasons for not participating Méjean et al 2014 [ 43 ] NutriNet-Santé Study Paris, France Evaluate relationships between participation motives and sociodemographic, health, and lifestyle characteristics of participants in cohort designed to identify nutritional risk or protective factors for chronic diseases Web-based, Prospective cohort study Nutrition Questionnaires assessing dietary intake, physical activity...…”

“…Overall, all studies provided information on recruitment rates and 19 provided information on retention rates [ 36 , 38 – 41 , 43 – 47 , 49 – 52 , 55 – 58 , 61 ] (Table 2 ). A variety of methods for male participant recruitment included advertising [ 36 , 43 , 54 , 57 ], letters of invitation [ 39 – 43 , 47 , 52 , 56 – 58 , 61 ], selection of participants from larger cohorts [ 42 , 43 , 50 , 53 ], or recruitment from hospitals or registers [ 37 , 44 , 48 , 51 , 54 , 57 ] (Table 3 ). The most common method was sending letters of invitation, used in 11 out of the 24 studies, and yielded recruitment rates between 4.4% and 79.3% [ 47 , 52 ].…”

“…A variety of methods for male participant recruitment included advertising [ 36 , 43 , 54 , 57 ], letters of invitation [ 39 – 43 , 47 , 52 , 56 – 58 , 61 ], selection of participants from larger cohorts [ 42 , 43 , 50 , 53 ], or recruitment from hospitals or registers [ 37 , 44 , 48 , 51 , 54 , 57 ] (Table 3 ). The most common method was sending letters of invitation, used in 11 out of the 24 studies, and yielded recruitment rates between 4.4% and 79.3% [ 47 , 52 ]. Irvine et al, recruited participants through letter of invitation and time space sampling, and reported that time space sampling was difficult, time consuming and only yielded one participant per 11 field visits [ 23 ].…”

Evidence from ClinicalTrials.gov on the growth of Digital Health Technologies in neurology trials

“…Interestingly, pharmaceutical companies tested self-developed DHTs in some trials [24][25][26] , indicating a possibility for broader prospective adoption by other stakeholders. Differences in the share of industry-sponsored trials across neurologic diseases could indicate differences in experience with digital measures across indications or difference in research funding for different diseases (either within firms themselves and/or from investments by research foundations or public funders).…”