Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Background: Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data. Objectives: To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS). To gain insights and recommendations from PlwMS on their experience with these PROs. Methods: We assessed 6 PROs (FSIQ-RMS, modified-FIS, MSQoL-54, Leeds 8-item MSQoL, MSIS-29 and EQ-5D) for alignment with regulatory and scientific requirements on PRO structure/development. PlwMS evaluated the degree to which the PROs reflect disease aspects they perceive important. Results: Definitions, clarifications and conceptualisations of the measurement variables were often lacking. PlwMS were variably involved in PRO development. Ethnic diversity was rarely documented. PlwMS identified individualisation, ease of understanding, time burden, and mode of administration as factors affecting PRO usability. Conclusions: To date, the PRO development process has consistently lacked clear definitions of concepts of interest, use of conceptual frameworks and patient involvement, thereby compromising the validity of data they generate. PRO instrument development must be conducted more robustly to maximise the value of pivotal clinical trials.

Innovating Care in Multiple Sclerosis: Feasibility of Synchronous Internet-Based Teleconsultation for Longitudinal Clinical Monitoring.

The 'coronavirus disease of 2019' crisis has recently forced an expedited adoption of teleconsultation (TC) in most medical domains. Short-term digital interventions have generally been associated with feasibility, clinical benefits, user satisfaction, and cost-effectiveness in patients with multiple sclerosis (MS) but outcomes after repeated utilization over extended periods need to be further evaluated. In this feasibility study, 60 subjects with MS were 1:1 randomized to receive standard care augmented by four TCs using an audiovisual Internet platform (intervention) versus standard care alone (controls), over a period of 12 months. Effects on functional status, medical costs, and satisfaction were explored as secondary outcomes. Eighty-nine out of 108 scheduled TCs (82.4%) were completed, and 26 patients could complete at least one TC (86.7%), meeting our prespecified feasibility target of 80%. The intervention did not lead to significant differences in functional status (with the potential exception of fatigue) nor medical costs. Most interventional patients declared themselves to be (very) satisfied about the quality of care and technical aspects associated with the TCs. Our results demonstrate that longitudinal clinical monitoring using real-time audiovisual TC over the Internet is feasible and well-received by patients with MS. Such an approach can be a promising new care strategy.

Global Peginterferon Beta-1a Tolerability Management Best Practices: A Nurse-Focused Delphi Approach.

INTRODUCTION: Injection site reactions (ISRs) and flu-like symptoms (FLS) are common in patients with relapsing forms of multiple sclerosis (MS) treated with peginterferon beta-1a. The purpose of this Delphi analysis was to explore peginterferon beta-1a discontinuation rates across MS treatment centers, to obtain consensus on effective mitigation and management strategies for ISRs and FLS, and to identify areas where additional training and education for nurses and patients could improve treatment outcomes. METHODS: In this modified Delphi process, an international steering committee of eight MS-certified nurses developed two rounds of surveys, which were completed by 262 and 188 MS nurses, respectively, representing nine countries. RESULTS: On average, nurses reported that 25% and 30% of patients treated with peginterferon beta-1a experienced ISRs and FLS, respectively. Discontinuation due to severe ISRs or FLS was most common in the first 6 months of treatment, yet follow-up visits typically took place 6 months after peginterferon beta-1a initiation. Preferred management strategies for ISRs included nonsteroidal anti-inflammatory drugs and rotation of the injection site, whereas preferred management strategies for FLS included acetaminophen/paracetamol and hydration/nutrition. Most nurses (77%) agreed that additional education and training on ISR and FLS management would bolster their confidence in treating patients with these symptoms. CONCLUSION: Delphi respondents reached consensus on ISR and FLS management strategies, which can help to inform treatment decisions. The results of this global Delphi analysis indicate that management of ISRs and FLS could be improved with more frequent follow-up visits and individualized training and education.

Feasibility of Real Time Internet-Based Teleconsultation in Patients With Multiple Sclerosis: Interventional Pilot Study.

BACKGROUND: Telemedicine (TM) is currently flourishing in rural and emergency settings, but its implementation in the routine management of chronic neurological disorders has developed with more hesitation. Limited access to specialized care facilities and expanding patient populations, combined with unprecedented mobility restrictions imposed by the coronavirus disease pandemic, are currently stressing the need for remote solutions in this field. Studies in patients with multiple sclerosis (MS) have been heterogeneous in objectives and methodology but generally support the concept that TM interventions produce clinical benefits, cost-effectiveness, and user satisfaction. Nonetheless, data on live interaction between patients and health care providers for MS teleconsultation purposes remain scarce. OBJECTIVE: The aim of this study is to demonstrate the feasibility of planned real time audiovisual teleconsultation over the internet for patients with MS. METHODS: A total of 20 patients with MS presenting at a specialized MS center in Belgium were recruited for this study. One teleconsultation was scheduled for each participant. Patients were provided a unique hyperlink by mail in advance, leading them automatically and directly to the virtual waiting room, where they could accept or decline our incoming call. All teleconsultations were performed by a trained medical student with the intention to keep the conversation similar to what is usually discussed during a classic face-to-face MS consultation; no remote physical exams were performed. The approach was considered feasible if at least 80% of the planned TM visits could be successfully completed at the foreseen moment. Patient satisfaction (technical quality, convenience, and overall quality of care) was evaluated at the end of each teleconsultation by means of 5-point Likert scales containing the categories very unsatisfied, unsatisfied, neutral, satisfied, and highly satisfied. RESULTS: Out of 20 consultations, 17 were successfully completed (85%). Failures were due to patients not responding (n=2) and technical issues (n=1). Out of the 17 consultations, 17 patients declared themselves satisfied or highly satisfied for technical quality, 15 patients for convenience, and 16 patients for overall quality of care. CONCLUSIONS: Planned real time audiovisual teleconsultation over the internet is feasible and highly appreciated in patients with MS. Incorporation of such services in routine clinical MS practice is expected to improve access to specialized care facilities for affected patients.

Correlations of health status indicators with perceived neuropsychological impairment and cognitive processing speed in multiple sclerosis.

BACKGROUND: Comorbidity and health behaviours may explain heterogeneity regarding cognitive performance in multiple sclerosis. Patient-reported cognitive difficulties have impact but do not consistently correlate with objective cognitive performance. Our study aims to investigate whether health status indicators including comorbidities, body mass index, physical activity, smoking, sleeping behaviour and consumption patterns for fish, alcohol and caffeinated drinks are associated with measures of subjective and objective cognitive performance. METHODS: Survey data on self-reported cognitive performance, assessed with the MS Neuropsychological Screening Questionnaire (MSNQ), were related to the presence of arterial hypertension, diabetes mellitus, cardiovascular and chronic renal diseases, hypercholesterolemia, depression based on 2-question screening tool, health and consumption behaviors. We included the Symbol Digit Modalities Test when available within 6 months as an objective, performance-based metric of cognitive processing speed. We investigated the interrelation between all variables with a Spearman correlation matrix and corrected for multiple testing. Regression models were built and controlled for age, sex and phenotype. RESULTS: We used available data from 751 patients with definite MS, including 290 SDMT scores within a time window of 6 months, to study relations between variables. MSNQ and SDMT scores were not significantly correlated. Correlation patterns for subjective and objective performance differed. Age, disease duration and physical disability correlated with SDMT scores only. Regression analyses could be performed for MSNQ scores in 595/751 (79.2%) and for SDMT scores in 234/751 (31.2%) participants. After restricting variables to avoid collinearity and adjusting for the number of variables, regression models explained 15% of the variance for subjective and 14% of the variance for objective cognitive performance. A higher number of physical comorbidities, reporting depressive symptoms, sleeping 9 h or more and daily use of sleeping medication were associated with lower subjective cognitive performance, whereas increasing age was associated with reduced processing speed. These associations persisted after correction for multiple testing. CONCLUSION: Increasing age is associated with reduced cognitive processing speed whereas comorbidities and sleep behaviors contribute to subjective cognitive performance.

Does including the full CVLT-II and BVMT-R improve BICAMS? Evidence from a Belgian (Dutch) validation study.

BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a fast, easy-to-administer and already widely validated neuropsychological battery for cognition in multiple sclerosis. OBJECTIVE: The goals of our study were to validate the BICAMS in a Belgian Dutch-speaking population and to investigate to what extent including extensive versions of two of the three BICAMS subtests improved its psychometric qualities. METHODS: Ninety-seven persons with MS and ninety-seven healthy controls were included and group-matched on age, education level and gender. All participants performed the BICAMS with an extensive version of the CVLT-II and BVMT-R. RESULTS: The SDMT and BVMT-R were able to dissociate between the MS and healthy control group, while the CVLT-II was not. Distributions of CVLT-II scores suggest learning effects in the MS group, indicating the need for alternative word lists or the construction of an adapted version fitted for repeated administration. Including the full CVLT-II and BVMT-R did not markedly improve the psychometric qualities of the BICAMS. CONCLUSION: This study validates the BICAMS in a Belgian Dutch-speaking population and facilitates the use of it in clinical practice, while providing evidence that including full versions of the CVLT-II and BVMT-R does not increase its psychometric qualities markedly.

The importance of a multi-disciplinary perspective and patient activation programmes in MS management.

BACKGROUND: Multiple sclerosis (MS) is a progressive disease associated with a large variety of symptoms and changing patients' needs during the disease course. In order to provide appropriate care in every disease stage and let patients live their lives to the full, a multi-disciplinary approach and patient activation is needed. OBJECTIVE: To summarise the multi-disciplinary perspective of MS, with focus on the organisation of a multi-disciplinary care team and possibilities to support patient activation. METHODS: This review reflects the content of the presentations, audience polling results and discussions on the multi-disciplinary perspective of MS during the second Pan-European MS Multi-stakeholder Colloquium. RESULTS: In many countries, the neurologist with or without the support of an MS nurse is responsible for the long-term care of MS patients. When needed, they should refer to other (non-)medical specialists. However, the patient should be empowered as well to manage his/her disease and to implement a physically active lifestyle in order to improve treatment outcomes and quality of life. CONCLUSION: To create equal access to care for MS patients across Europe, evidence-based standards of care, symptom self-monitoring tools and educational programmes for patients and healthcare professionals including non-medical treatment strategies should be developed at the European level.