Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice.

IntroductionAdvances in wearable sensor technology now enable frequent, objective monitoring of real-world walking. Walking-related digital mobility outcomes (DMOs), such as real-world walking speed, have the potential to be more sensitive to mobility changes than traditional clinical assessments. However, it is not yet clear which DMOs are most suitable for formal validation. In this review, we will explore the evidence on discriminant ability, construct validity, prognostic value and responsiveness of walking-related DMOs in four disease areas: Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease and proximal femoral fracture.Methods and analysisArksey and O’Malley’s methodological framework for scoping reviews will guide study conduct. We will search seven databases (Medline, CINAHL, Scopus, Web of Science, EMBASE, IEEE Digital Library and Cochrane Library) and grey literature for studies which (1) measure differences in DMOs between healthy and pathological walking, (2) assess relationships between DMOs and traditional clinical measures, (3) assess the prognostic value of DMOs and (4) use DMOs as endpoints in interventional clinical trials. Two reviewers will screen each abstract and full-text manuscript according to predefined eligibility criteria. We will then chart extracted data, map the literature, perform a narrative synthesis and identify gaps.Ethics and disseminationAs this review is limited to publicly available materials, it does not require ethical approval. This work is part of Mobilise-D, an Innovative Medicines Initiative Joint Undertaking which aims to deliver, validate and obtain regulatory approval for DMOs. Results will be shared with the scientific community and general public in cooperation with the Mobilise-D communication team.RegistrationStudy materials and updates will be made available through the Center for Open Science’s OSFRegistry (https://osf.io/k7395).

Background The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration ISRCTN12051706.

Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a “resetting” of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting.

Background Measuring mobility in daily life entails dealing with confounding factors arising from multiple sources, including pathological characteristics, patient specific walking strategies, environment/context, and purpose of the task. The primary aim of this study is to propose and validate a protocol for simulating real-world gait accounting for all these factors within a single set of observations, while ensuring minimisation of participant burden and safety. Methods The protocol included eight motor tasks at varying speed, incline/steps, surface, path shape, cognitive demand, and included postures that may abruptly alter the participants’ strategy of walking. It was deployed in a convenience sample of 108 participants recruited from six cohorts that included older healthy adults (HA) and participants with potentially altered mobility due to Parkinson’s disease (PD), multiple sclerosis (MS), proximal femoral fracture (PFF), chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF). A novelty introduced in the protocol was the tiered approach to increase difficulty both within the same task (e.g., by allowing use of aids or armrests) and across tasks. Results The protocol proved to be safe and feasible (all participants could complete it and no adverse events were recorded) and the addition of the more complex tasks allowed a much greater spread in walking speeds to be achieved compared to standard straight walking trials. Furthermore, it allowed a representation of a variety of daily life relevant mobility aspects and can therefore be used for the validation of monitoring devices used in real life. Conclusions The protocol allowed for measuring gait in a variety of pathological conditions suggests that it can also be used to detect changes in gait due to, for example, the onset or progression of a disease, or due to therapy. Trial registration: ISRCTN—12246987.

In carefully selected patients, autologous haematopoietic stem cell transplantation (HSCT) is a safe, highly effective and cost-saving treatment modality for treatment-resistant, and potentially treatment-naïve, immune-mediated neurological disorders. Although the evidence base has been growing in the last decade, limited understanding has led to confusion, mistrust and increasing use of health tourism. In this article, we discuss what autologous HSCT is, which immune-mediated conditions can be treated with it, how to select patients, what are the expected outcomes and potential adverse effects, and how cost-effective this treatment is.

BackgroundThe development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisionsMethods/DesignThe Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall- related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability.DiscussionThe results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost- effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility.Trial registrationISRCTN12051706

UNSTRUCTURED Mobility is an important indicator of physical health. As such there is potential clinical value in being able to measure mobility accurately in a person’s home and daily life environment to help researchers and clinicians to better track changes and patterns in a person’s daily lives and activities. To do this, there is a need to create new ways of measuring walking. Recent advancements in digital technology are helping researchers to do this. However, before any new measure can be used, researchers, healthcare professionals and regulators need to know that the digital method is accurate and that it is both accepted and produces meaningful outcomes for the patients and clinicians. Researchers must therefore include patients, or members of patient organisations, in the development of such new tools in a process known as patient and public involvement and engagement (PPIE). Although the value and importance of PPIE activities is well-known, little guidance exists on how to do this in a meaningful way. This is particularly true within large research consortia that target multiple objectives, include multiple patient groups and work across many countries. Without clear guidance, the risk is that PPIE does not capture patient opinions and needs correctly, thereby reducing the usefulness and effectiveness of new tools. Mobilise-D is an example of such a large research consortium, that is looking to develop new digital outcome measures for real-world walking in patients with Parkinson’s Disease, Multiple Sclerosis, Chronic Obstructive Pulmonary Disease, and Proximal Femoral Fracture. This paper outlines how PPIE structures were developed in this consortium, providing detail about how this happened, the steps taken to implement PPIE, the experiences PPIE contributors have had within this process, the lessons learned from it, and recommendations for others who may want to do similar work in the future. The work outlined within this paper has provided the Mobilise-D consortium with a foundation from which future PPIE tasks can be created and managed with clearly defined collaboration between researchers and patient representatives across Europe. This paper provides guidance around the work required to set up PPIE structures within a large consortium, to promote and support the creation of meaningful and efficient PPIE related to the development of digital mobility outcomes.