Toward a regulatory qualification of real-world mobility performance biomarkers in Parkinson’s patients using Digital Mobility Outcomes

Wearable inertial sensors can be used to monitor mobility in real-world settings over extended periods. Although these technologies are widely used in human movement research, they have not yet been qualified by drug regulatory agencies for their use in regulatory drug trials. This is because the first generation of these sensors was unreliable when used on slow-walking subjects. However, intense research in this area is now offering a new generation of algorithms to quantify Digital Mobility Outcomes so accurate they may be considered as biomarkers in regulatory drug trials. This perspective paper summarises the work in the Mobilise-D consortium around the regulatory qualification of the use of wearable sensors to quantify real-world mobility performance in patients affected by Parkinson’s Disease. The paper describes the qualification strategy and both the technical and clinical validation plans, which have recently received highly supportive qualification advice from the European Medicines Agency. The scope is to provide detailed guidance for the preparation of similar qualification submissions to broaden the use of real-world mobility assessment in regulatory drug trials

A roadmap to inform development, validation and approval of digital mobility outcomes: the Mobilise-D approach

Health care has had to adapt rapidly to COVID-19, and this in turn has highlighted a pressing need for tools to facilitate remote visits and monitoring. Digital health technology, including body-worn devices, offers a solution using digital outcomes to measure and monitor disease status and provide outcomes meaningful to both patients and health care professionals. Remote monitoring of physical mobility is a prime example, because mobility is among the most advanced modalities that can be assessed digitally and remotely. Loss of mobility is also an important feature of many health conditions, providing a read-out of health as well as a target for intervention. Real-world, continuous digital measures of mobility (digital mobility outcomes or DMOs) provide an opportunity for novel insights into health care conditions complementing existing mobility measures. Accepted and approved DMOs are not yet widely available. The need for large collaborative efforts to tackle the critical steps to adoption is widely recognised. Mobilise-D is an example. It is a multidisciplinary consortium of 34 institutions from academia and industry funded through the European Innovative Medicines Initiative 2 Joint Undertaking. Members of Mobilise-D are collaborating to address the critical steps for DMOs to be adopted in clinical trials and ultimately health care. To achieve this, the consortium has developed a roadmap to inform the development, validation and approval of DMOs in Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease and recovery from proximal femoral fracture. Here we aim to describe the proposed approach and provide a high-level view of the ongoing and planned work of the Mobilise-D consortium. Ultimately, Mobilise-D aims to stimulate widespread adoption of DMOs through the provision of device agnostic software, standards and robust validation in order to bring digital outcomes from concept to use in clinical trials and health care

Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device

This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application. Trial registration: ISRCTN – 12246987

Het anthrachinonproces met biokatalyse ter bereiding van waterstofperoxide

Document(en) uit de collectie Chemische Procestechnologie.DelftChemTechApplied Science

Beyond TRL – Understanding institutional readiness for implementation of nature-based solutions

This paper explores the concept of “institutional readiness” (IR) applied to the adoption and mainstreaming of Nature-based solutions (NBS) to deal with climate related risks. We argue that barriers towards up-scaling and mainstreaming of NBS are a manifestation of uncertainty, and are often associated with the ‘readiness’ of the institutional setting rather than with the readiness of the NBS technology itself. We align the concepts of Institutional Readiness (IR) to the more widely used concept of Technology Readiness Level (TRL) to understand drivers and barriers for adoption of NBS and analyse the role of institutional capacity. We illustrate this with the case study of the Urban Water Buffer Spangen in Rotterdam, the Netherlands, which is an NBS with high TRL. To do so, we constructed a timeline of the design and implementation process of the NBS, identifying and classifying key uncertainties as well as the strategies applied to deal with these uncertainties, particularly in the institutional context. Our results indicate that for mainstreaming of NBS, Institutional Readiness (IR) should be at a degree where strategies to deal with uncertainties in institutional, organizational and governance contexts can be integrated in the design and planning process. We claim that the concept of IR should be considered in its role to deal with uncertainty, in order to close the documented gap of NBS implementation and mainstreaming.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Water Resource