Multiple sclerosis (MS) is a chronic neurological disease associated with inflammation and neurodegeneration. Its worldwide prevalence is estimated at 2.5 million people affected, and it is the most common cause of disability in young adults, aside from trauma [1-3]. Disease monitoring in people with MS encompasses continuous evaluation of the following three major components: clinical disease activity, radiological disease activity, and, albeit mostly for research purposes, biomarkers [4,5]. These outcomes can be summarized as clinician-reported outcomes. They represent the mainstay in determining the disease course and treatment response in routine MS care and are also the main endpoints in clinical trials. Complementary to clinician-reported outcomes, so-called patient-reported outcomes (PROs) are reports from patients concerning their own health perception, quantifying either specific symptoms that are hard to objectify, such as fatigue, depression, and sexual dysfunction, or more general parameters, such as quality of life, working abilities, treatment adherence, and treatment satisfaction. Over the past few years, PROs have contributed to displaying the disease burden in MS and its impact on health-related quality of life. So far, several PRO measures (PROMs) for MS have been validated and established, such as scores for quality of life, fatigue, and sexual functioning [6,7].

While garnering information about a patient’s subjective impairment to health through PROs would theoretically have a palpable benefit, application in routine care is greatly hindered. Currently, filling out and evaluating paper-based PRO questionnaires are consuming a considerable amount of resources in terms of time and personnel. Thus, useful ways to conveniently introduce PROs into clinical practice are needed.

The use of mobile health (mHealth) may offer strategies for easily administered PRO questionnaires. This could facilitate research and advance the focus from merely reporting disease parameters to understanding an individual’s impairment caused by disease. So far, a recognizable effort has been made to offer mHealth technologies for managing MS. These solutions can be summarized as elements of (1) screening and assessment, (2) treatment and rehabilitation, (3) advice and education, and (4) disease monitoring and management [8]. However, only a handful of these tools focus on integrating validated PROs into clinical practice. One smartphone app, for example, offers remote and active testing of surrogate markers for dexterity and mobility that correlated well with on-site administered tests [9]. Another study investigated an on-site tablet-based method for evaluating bladder control [10]. The most prominent mHealth solution for remote patient monitoring in people with MS is probably the Multiple Sclerosis Performance Test. It is a tablet-based tool designed to measure physical disability, and it has spurred a lot of interest and subsequent adaptions [11,12]. Nevertheless, solutions that allow remote tracking of well-established PROMs in MS have not yet been reported.

The aim of this report is to introduce haMSter as an mHealth-based solution for tracking PROs in people with MS remotely. Through the use of the haMSter app, patients are offered an opportunity to fill out PRO questionnaires anywhere and anytime they feel comfortable. The scoring algorithm of haMSter provides neurologists a unique opportunity to visualize the longitudinal course of their patients’ PROs. A pilot study evaluating the feasibility of the haMSter protocol is currently ongoing.

This study protocol will be used in an uncontrolled pilot trial evaluating adherence to the haMSter app in 50 people with MS. Upon informed consent to participate in this study, eligible patients will be able to download the app on their smartphones during a regular visit to our MS clinic and use it at home over a period of 6 months.

This is a monocentric study at the MS Clinic of the Department of Neurology, Medical University of Vienna, Austria. An outline of the study protocol is shown in Figure 1 [13]. Patients are instructed to fill out three specific PRO questionnaires (“haMStercare”) on their smartphone once every 30 days. In addition, patients are introduced to two other features of haMSter, which are available at their own convenience. These are a reminder for taking their medication (“haMSterreminder”) and a diary (“haMSterdiary”). At the follow-up visit, a Bluetooth printer in the exam room will allow the patient to print out a PRO score sheet that graphically shows the score for each PRO over the course of the study. This illustration is intended as a base for discussing symptoms and the patient’s individual health perception. The study concludes with the administration of a paper-based satisfaction questionnaire including a validated outcome measure for satisfaction with telemedicine (Telemedicine Perception Questionnaire [TMPQ] [14]) and an empirical questionnaire. The latter collects user feedback regarding technical implementation, design, handling, and possibilities for further improvement of the app’s utility.

The programming of the haMSter app has been funded through an unrestricted grant by pharmaceutical companies marketing medication for the treatment of MS. A study outline was sent out to all companies with branches in Austria at that time (Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva-Ratiopharm). Out of these seven companies, five agreed to cover the costs for programming the app (Biogen, Merck, Roche, Sanofi-Genzyme, and Teva-Ratiopharm Austria). A sponsorship agreement was signed between the inventor of the app and a sponsoring company’s representative. Funding parties were not involved in any decisions regarding any content of the app, the study protocol and design, or any matter concerning the pilot study itself at any point in time. As for the PRO questionnaires included in haMSter, the proprietors of the German versions of the HADS and FSMC received financial compensation for the use of their questionnaires in the pilot study and signed a licensing agreement. The amount of this compensation was calculated based on the frequency of access to the respective questionnaire (ie, 50 patients, once a month over 6 months). The author of the German version of the MSIS-29 kindly offered its use for free.

The idea for the haMSter app was conceived in November 2018. The coding process began in May 2019 and was finished in October 2019. After a period of beta testing and some delay due to the COVID-19 pandemic, the pilot study was launched in April 2020 (“first patient in”), and it is expected to end in April 2021 (“last patient out”).

To provide an overview of the patients participating in this pilot study, we will report typical baseline and sociodemographic characteristics documented at baseline and follow-up. The structure is provided in Textbox 1 [18].

The primary outcome measure is the adherence to filling out the questionnaires once per month. Results will be displayed as the mean percentage of filled out questionnaires based on the PRO scoring sheet. Figure 4 illustrates a sample scoring sheet as viewed in the app and as a printout that is presented to the patient and discussed with the physician during the end of the study visit. We will investigate whether adherence decreases over time by using the Friedman test and Jonckheere-Terpstra test for monotonic trend.

Exploratory outcome measures include patient perceptions of this new mHealth method based on mean TMPQ values. There will also be a further exploratory analysis of PROs in conjunction with MS disease characteristics and of the empirical questionnaires with respect to the utility and design of haMSter. If reasonable, we will perform a subgroup analysis to identify patients with high (75th percentile) and low (25th percentile) satisfaction. Another secondary goal is group comparisons of adherence between patients with and those without upper extremity disability as defined by the Expanded Disability Status Scale (EDSS) score.

Currently, there is no consensus on a significant threshold for adherence to mHealth methods. With respect to our main outcome measure, we regard a minimum adherence of 50% or higher as relevant (participants completed the three PRO questionnaires [a total of 63 questions] three times over a period of 6 months). As for the exploratory outcome measures, we aim to provide descriptive statistics (categorical variables expressed as frequencies and percentages, and continuous variables tested for normal distribution by the Kolmogorow-Smirnow test and presented as mean and standard deviation or median and interquartile range as appropriate).

The ethics committee at the Medical University of Vienna, Austria, approved this study in September 2019 (EK1798/2019). Written informed consent will be obtained from each patient, and the study protocol follows the guidelines set by the Declaration of Helsinki. The trial has been registered at ClinicalTrials.gov (identifier: NCT04555863).