MSProDiscuss™ for Identifying Multiple Sclerosis Progression: Comparison
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Please note this is a comparison between Version 2 by Jessie Wu and Version 1 by Tjalf Ziemssen.

Multiple sclerosis (MS) is a chronic, potentially debilitating autoimmune-mediated neurological disorder of the central nervous system (CNS) and the most common acquired degenerative disease of the CNS in young adults. MSProDiscuss, developed with physicians and patients, facilitates a structured approach to patient consultations. It analyzes multidimensional data via an algorithm to estimate the likelihood of progression (the MSProDiscuss score), the contribution of various symptoms, and the impact of symptoms on daily living, enabling a more personalized approach to treatment and disease management. Data from clinical decision support (CDS) tools such as MSProDiscuss offer new insights into disease course and facilitate informed decision-making and a holistic approach to MS patient care. 

  • multiple sclerosis
  • MS progression
  • MSProDiscuss

1. The Importance and Potential Challenges of Early Identification of MS Progression

Early identification of progression in MS is key because disability progression can start early in the disease course, and delays to intervention with DMTs can have a significant impact on long-term prognosis and patient QoL [27,30][1][2]. The window of opportunity for interventional treatment to limit irreversible damage is small [41][3] and therefore a sensitive tool capable of detecting the early signs of disease progression is essential to maximize long-term brain health [34,38,39,40,41][3][4][5][6][7].
For a tool to effectively identify the progression of MS, multiple aspects of the disease should be considered, such as aspects of daily living and patient clinical history [42,43,44][8][9][10]. Such aspects are frequently overlooked, though research has shown that they provide neurologists with a deeper understanding of their patient’s health status [42,43][8][9]. Some composite outcome measures are effective for the detection of a broad range of clinical manifestations and can be more sensitive than measuring a single outcome such as an MRI endpoint, relapse, or disability level [24][11]. In concept elicitation interviews, physicians indicated a desire for a tool sensitive enough to effectively assist clinicians with the identification of MS progression [34][4]. Therefore, one of the challenges was to develop an algorithm able to convert complex qualitative data (from multiple domains assessed in consultation with a patient with MS, e.g., subjective symptoms, impact on QoL) into quantitative data, thereby allowing rapid, non-subjective data analysis to estimate the likelihood of progression and track longitudinal changes [38][5].
The MSProDiscuss tool has been developed for neurologists to use in structured consultations with their patients, to assist in monitoring the risk of progression by quantitatively assessing multidimensional data, including patient history, and to score the likelihood of progression through the use of an algorithm [34,38,39,40][4][5][6][7]. A recent study following regular use of MSProDiscuss in consultations (i.e., every 6 months) demonstrated that the tool allowed HCPs to accurately track longitudinal changes in multiple dimensions in individual patients [40][7].

2. Overview of the Development of MSProDiscuss

MSProDiscuss was developed in four stages in partnership with patients (stage 1) and HCPs (stages 1–4), as described below and summarized in Figure 1 [34,38,39,40][4][5][6][7].
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Figure 1. Stages in the development of the MSProDiscuss tool [34,38,39,40][4][5][6][7]. EDSS, expanded disability status scale; F2F, face-to-face; HCP, healthcare provider; RRMS, relapsing–remitting MS; SPMS, secondary progressive MS.

3.1. Stage 1

2.1. Stage 1

The initial stage of MSProDiscuss development was to characterize the key symptoms that impact the transition from RRMS to SPMS. This was conducted using a mixed model approach, involving patient interviews and multivariate analysis of real-world data. The findings informed the selection of the key variables to be included in a questionnaire pilot tool [34][4].

2.2. Stage 2

A draft scoring algorithm was developed to determine the relevance and importance of each of the questionnaire items created in Stage 1. A novel and comprehensive approach was used to develop this draft algorithm, using data obtained from quantitative analysis of a real-world observational study, ranking and weighting exercises of variables contributing to progression, and qualitative interviews with experienced neurologists [38][5].

2.3. Stage 3

A total of 20 experienced neurologists completed a draft tool, based on interviews with 198 patients with MS (with confirmed RRMS [n = 89], with SPMS [n = 62], and suspected of transitioning to SPMS [n = 47]). These results were used to determine cut-off values and corresponding sensitivity and specificity for RRMS and SPMS identification. Excellent inter-rater reliability (intraclass correlation coefficient: 0.95 [95% CI 0.77–1.00]) and good evidence of construct validity suggested that the factors used by the draft MSProDiscuss algorithm were relevant indicators of early signs of disease progression in MS [39][6].

2.4. Stage 4

HCPs (n = 301) across 34 countries tested the MSProDiscuss tool during consultations with approximately 7000 patients with MS (n = 6974), of whom 77% (n = 5370) had RRMS. Following each consultation, the HCPs completed an initial individual questionnaire to assess the comprehensibility, usability, and usefulness of MSProDiscuss. At the end of the study, the HCPs completed a final questionnaire to capture their overall experience in using the tool, including their thoughts on its comprehensibility, usability, usefulness, and integration and adoption into clinical practice. Results from the two surveys showed that 97–98% of HCPs completed the tool within 1–4 min, and 86% were willing to integrate MSProDiscuss into their daily clinical practice. MSProDiscuss was viewed as usable and useful for facilitating clinician–patient discussions regarding MS disease progression [40][7].

3. Other Tools for Assessment of MS Progression

MSProDiscuss is not the only tool designed to support the identification of the risk of disease progression in patients with MS. The YourMSQuestionnaire (YMSQ), a 20-question patient-completed tool co-developed with patients with MS, patient advocacy groups, and clinicians has been designed to facilitate and standardize discussions between clinicians and patients [55][12]. The YMSQ collects patient perspectives on changes in MS symptoms, relapses, and the impact of MS on daily living activities that have occurred in the previous 6 months [56][13]. Patient-completed tools such as YMSQ empower patients to become involved in decision-making by ensuring that they are aware of the information that they need to participate [35][14]. Use of the YMSQ by patients could be paired with, and complementary to, the use of MSProDiscuss by the neurologist in consultations. The YMSQ helps patients to be well-prepared, having reflected on their symptoms, potentially resulting in faster and more comprehensive input of data into MSProDiscuss. Another tool of interest is the SPMS Nomogram Nordics. This nomogram has been developed for research purposes to calculate the risk of a patient transitioning from RRMS to SPMS within 10, 15, and 20 years after onset of RRMS. The aim of this tool is to assist with decision-making and patient counseling in the initial phase of MS, prompting early and effective treatment for patients with a worse prognosis [57][15].

4. Future Applications of New Technologies in MS

The use of telemedicine appointments and digital tools in clinical settings has increased in recent years, mainly due to the coronavirus disease (COVID-19) pandemic [58,59][16][17]. In a recent survey of 613 patients with MS, 54% stated that they would be open to telemedicine appointments with neurologists and an unmet need for digital tools tailored to patients with MS was highlighted [60][18]. As MSProDiscuss is web-based, it was tested during the COVID-19 pandemic and showed promise in assisting with remote visits in which lack of face-to-face interaction can be a barrier to HCP–patient communication [40][7]. It is increasingly recognized that digital tools such as MSProDiscuss could facilitate a more in-depth assessment of disease evolution and progression when frequent visits to the doctor are not possible [58][16]. Tools developed for physicians, together with tools aimed at patients, have the potential to complement and facilitate more detailed and effective management of MS, promote shared decision-making, and empower patients by involving them in the management of their own disease [56][13]. Currently, telemedicine appointments remain a feasible option, especially for those who must travel to attend hospital appointments or who struggle with reduced mobility [59][17]. Having a digital tool that can capture the patient history and estimate the likelihood of progression remotely may improve patient outcomes by enabling appropriate assessment when face-to-face appointments are not feasible. It has been postulated that, in the future, integration of data from multiple sources could accurately capture a patient’s characteristics, with the aim of enabling accurate modeling of disease progression and treatment simulation. This concept has been dubbed the “digital twin” [61][19]. Through use of an appropriate dashboard, the “twin” could facilitate discussions of pre-analyzed patient data/projections with patients, physician–patient communication, and shared decision-making [61][19]. The deep clinical phenotyping of patients with MS offered by the MSProDiscuss tool is a step towards the realization of the MS digital twin concept. Another way by which new technologies can be utilized, and existing technologies further leveraged, is through integration into the EHR. For example, integration of the algorithm based on MSProDiscuss could facilitate longitudinal follow-up when included as part of the clinician’s routine assessment. The use of comprehensive monitoring systems in the real world to integrate clinical, paraclinical, and patient-reported outcome data from EHRs, local databases, and patient registries could also enable a more detailed, granular description of the long-term benefits and safety of DMTs [62][20].

References

  1. Giovannoni, G.; Butzkueven, H.; Dhib-Jalbut, S.; Hobart, J.; Kobelt, G.; Pepper, G.; Sormani, M.P.; Thalheim, C.; Traboulsee, A.; Vollmer, T. Brain health: Time matters in multiple sclerosis. Mult. Scler. Relat. Disord. 2016, 9 (Suppl. S1), S5–S48.
  2. Katz Sand, I.; Krieger, S.; Farrell, C.; Miller, A.E. Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis. Mult. Scler. 2014, 20, 1654–1657.
  3. Klinsing, S.; Yalachkov, Y.; Foerch, C. Difficulty in identification of patients with active secondary progressive multiple sclerosis by clinical classification tools. Eur. J. Neurol. 2022, 29, 1100–1105.
  4. Ziemssen, T.; Tolley, C.; Bennett, B.; Kilgariff, S.; Jones, E.; Pike, J.; Tomic, D.; Piani-Meier, D.; Lahoz, R. A mixed methods approach towards understanding key disease characteristics associated with the progression from RRMS to SPMS: Physicians’ and patients’ views. Mult. Scler. Relat. Disord. 2020, 38, 101861.
  5. Tolley, C.; Piani-Meier, D.; Bentley, S.; Bennett, B.; Jones, E.; Pike, J.; Dahlke, F.; Tomic, D.; Ziemssen, T. A Novel, Integrative Approach for Evaluating Progression in Multiple Sclerosis: Development of a Scoring Algorithm. JMIR Med. Inform. 2020, 8, e17592.
  6. Ziemssen, T.; Piani-Meier, D.; Bennett, B.; Johnson, C.; Tinsley, K.; Trigg, A.; Hach, T.; Dahlke, F.; Tomic, D.; Tolley, C.; et al. A Physician-Completed Digital Tool for Evaluating Disease Progression (Multiple Sclerosis Progression Discussion Tool): Validation Study. J. Med. Internet Res. 2020, 22, e16932.
  7. Ziemssen, T.; Giovannoni, G.; Alvarez, E.; Bhan, V.; Hersh, C.; Hoffmann, O.; Oreja-Guevara, C.; Robles-Cedeño, R.R.; Trojano, M.; Vermersch, P.; et al. Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey. J. Med. Internet Res. 2021, 23, e29558.
  8. Visser, L.A.; Louapre, C.; Uyl-de Groot, C.A.; Redekop, W.K. Health-related quality of life of multiple sclerosis patients: A European multi-country study. Arch. Public Health 2021, 79, 39.
  9. Baumstarck, K.; Boyer, L.; Boucekine, M.; Michel, P.; Pelletier, J.; Auquier, P. Measuring the quality of life in patients with multiple sclerosis in clinical practice: A necessary challenge. Mult. Scler. Int. 2013, 2013, 524894.
  10. Bass, A.D.; Van Wijmeersch, B.; Mayer, L.; Mäurer, M.; Boster, A.; Mandel, M.; Mitchell, C.; Sharrock, K.; Singer, B. Effect of Multiple Sclerosis on Daily Activities, Emotional Well-being, and Relationships: The Global vsMS Survey. Int. J. MS Care 2020, 22, 158–164.
  11. Inojosa, H.; Schriefer, D.; Ziemssen, T. Clinical outcome measures in multiple sclerosis: A review. Autoimmun. Rev. 2020, 19, 102512.
  12. The Your MS Questionnaire. Available online: https://www.yourms.com/#/welcome (accessed on 18 May 2022).
  13. Giovannoni, G.; Alvarez, E.; Hoffmann, O.; Oreja-Guevara, C.; Vermersch, P.; Khwaja, M.; Stadler, B.; Vandercappellen, J.; Ziemssen, T. Development of Your MS Questionnaire: A Patient-completed Digital Tool to Monitor Multiple Sclerosis Disease Symptoms and Their Impact on People’s Life. Poster P119. In Proceedings of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), 13–15 October 2021; Available online: https://www.medcommshydhosting.com/MSKnowledgecenter/ectrims/2021/posters/P119_ECTRIMS2021.pdf (accessed on 18 May 2022).
  14. Sutton, R.T.; Pincock, D.; Baumgart, D.C.; Sadowski, D.C.; Fedorak, R.N.; Kroeker, K.I. An overview of clinical decision support systems: Benefits, risks, and strategies for success. NPJ Digit. Med. 2020, 3, 17.
  15. Manouchehrinia, A.; Zhu, F.; Piani-Meier, D.; Lange, M.; Silva, D.G.; Carruthers, R.; Glaser, A.; Kingwell, E.; Tremlett, H.; Hillert, J. Predicting risk of secondary progression in multiple sclerosis: A nomogram. Mult. Scler. 2019, 25, 1102–1112.
  16. Ziemssen, T.; Haase, R. Digital Innovation in Multiple Sclerosis Management. Brain Sci. 2021, 12, 40.
  17. Zasadzka, E.; Trzmiel, T.; Pieczyńska, A.; Hojan, K. Modern Technologies in the Rehabilitation of Patients with Multiple Sclerosis and Their Potential Application in Times of COVID-19. Medicina 2021, 57, 549.
  18. Landi, D.; Ponzano, M.; Nicoletti, C.G.; Cola, G.; Cecchi, G.; Grimaldi, A.; Mataluni, G.; Mercuri, N.B.; Sormani, M.P.; Pacileo, G.; et al. Patient’s point of view on the use of telemedicine in multiple sclerosis: A web-based survey. Neurol. Sci. 2022, 43, 1197–1205.
  19. Voigt, I.; Inojosa, H.; Dillenseger, A.; Haase, R.; Akgün, K.; Ziemssen, T. Digital Twins for Multiple Sclerosis. Front. Immunol. 2021, 12, 669811.
  20. Matthews, P.M.; Block, V.J.; Leocani, L. E-health and multiple sclerosis. Curr. Opin. Neurol. 2020, 33, 271–276.
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