Table 5.

Current unanswered questions in motor neuron disease (MND) actigraphy research and future recommendations, ranked in terms of perceived importance.

Question	What is known so far?	Recommendation
User-related: are these devices and procedures feasible for use by people living with MND?	Adherence is good, and participants largely thought the devices were acceptable and reported a low burden of use.	Research to explore people’s lived experience of using the devices. Qualitative research methods will enable in-depth exploration of feasibility and allow identification of barriers and facilitators to using digital technologies.
User-related: are the devices and procedures feasible for family members, caregivers, and health care professionals?	Research has not comprehensively explored the experiences of individuals using the devices and procedures.	Research to explore experiences and perceptions of these individuals. Qualitative research methods will be helpful in identifying barriers and facilitators.
Clinical practice-related: is physical behavior related to other symptoms of MND?	Physical behavior is only a small part of MND, and no research has investigated relationships with other relevant disease domains.	Research to explore whether physical behavior is related to other objective measure areas (eg, respiratory function and muscle strength).
Clinical practice-related: are physical behavior end points more sensitive measures of disease-related change in physical function than the ALSFRS-R?	The evidence is inconclusive. Some studies have found that accelerometry data have greater variability than the ALSFRS-Ra, while others found less variability than the ALSFRS-R.	Research to quantify variability in physical behavior end points relative to that in ALSFRS-R. Consideration of effects of different MND phenotypes on measurement variability will be required here, as well as estimation of clinically meaningful effect size.
Methods-related: what is the optimum follow-up design to capture changes in physical behavior?	There is no consensus on the duration of follow-up, frequency of measurement, or duration of measurement. A measurement period of 7 days can account for potential day-to-day variation in physical behavior.	Research to identify the optimum durations of follow-up, frequency of measurement, and length of measurement. Using qualitative methods to explore people’s experiences of this will also contribute to our knowledge of what is feasible for patients and health care professionals.
Methods-related: what is the most optimal wear location to capture and predict changes in physical behavior with MND progression?	The wrist location correlated better with the ALSFRS-R fine motor domain and lower limb placement (hip or ankle) correlated better with the gross motor domain. Physical behavior end points may need to vary based on device wear location.	Research to identify optimal wear locations, including consideration of impacts on use of other devices or collection of additional data (eg, pulse oximetry). Studies should consider ease of use and participant burden and impacts of their evolution with disease progression.
Methods-related: is there an optimum device location and outcome measure for each MND phenotype?	Research has not investigated whether there are differences in outcome measures between MND phenotypes.	Research to explore inertial measurement unit performance, optimum wear location, and physical behavior end points across MND phenotypes.
Clinical practice-related: does monitoring physical behavior offer a cost-effective means of assessing change in physical function?	Research has not explored the cost implications or economics associated with using physical behavior end points.	Research evaluating the cost-effectiveness of using physical behavior end points in both clinical trials and in care is required.
Clinical practice-related: do physical behavior end points provide information that is clinically relevant or related to clinical milestones?	Research has not explored the impact of physical behavior end points on clinical decision-making, nor relationships to milestones (eg, loss of ambulation or care dependency).	Research to explore how using devices will impact clinical decision-making. Future studies should aim to establish minimum clinically important differences and minimal detectable change values for commonly used physical behavior end points. Qualitative research methods will be helpful for exploring this in depth.

^cALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised.