Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines; (2) inadequate conceptualization of dose, which is multidimensional; and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain individual sessions and episodes that can be active (time on task) or inactive (time off task), and each individual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.

Introduction: Despite an increase in the quality of clinical trials in stroke recovery, interventions have failed to markedly impact the trajectory of recovery after stroke. Failure may be due to the lack of consideration for the complexity of dose and its articulation within research trials. Prior to commencing the scoping review, we identified two research gaps to be addressed. Firstly, transparent application of a multidimensional definition of dose to clinical trial phases and secondly, the development of a quality tool to critique the articulation of dose across the pipeline. Building on this, we present the protocol for a scoping review that aims to synthesis what is known about dose articulation in stroke recovery in preclinical and clinical populations, and characterize research designs and statistical approaches used in dose articulation trials, and the associated advantages and disadvantages.Methods: The scoping review will apply Arksey and O'Malley's methodological framework. Two systematic searches that target preclinical and clinical literature will be run in Medline and Embase, which will be complimented by consultation with field experts and hand searching of included trials and relevant reviews. Search results will be imported into Covidence for transparent management. One reviewer will screen all abstracts and titles. Two reviewers will screen full text and a third reviewer included to resolve discrepancies. A standardized data charting form will be used to extract information and appraise the intervention description, risk of bias, and quality of both preclinical and clinical studies. Results will be summarized in tabular and narrative format to inform the development of recommendations for future research. Ethics approval is not required as data used will be secondary and de-identified.Conclusion: Development of a new quality tool to appraise the quality of both preclinical and clinical dose studies may serve to strengthen collaborative efforts between the fields. The findings from this review will advance the use of a discovery pipeline in stroke recovery research to ultimately inform clinical practice.

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22–66) and study sample size remains small (median n=30, IQR 20–48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1–7 days), 176 early subacute (8–90 days), 34 late subacute (91–180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600–1430) min/session, 1 (IQR, 1–1) session/d, 5 (IQR, 5–5) d/wk for 4 (IQR, 3–5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.

1 AbstractPurpose: The Disabilities of Arm, Shoulder and Hand (DASH) questionnaire is a patient reported outcome measure for evaluating upper limb function in people with musculoskeletal conditions. While the DASH has good psychometric properties when used with people with musculoskeletal conditions, it has not been tested with adults after stroke.Methods: Data for n=61 adults following stroke (aged 32 to 93 years, 44% male) were analysed to test validity and reliability of the DASH for use with a stroke population. Data Conclusion:The DASH is considered to have acceptable validity when used with adults following stroke. Test-retest reliability was low but further research is needed to establish whether this is a result of condition-related change or the stability of the measure.

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Introduction: Broadening eligibility criteria has been a focus to increase the generalisability of trial findings. Using upper limb motor trials conducted early post-stroke as the illustrative domain, we sought to (a) investigate whether the published aim and conclusion statements adequately reflect the generalisability of findings and, (b) explore internal validity and feasibility as constraints to achieving generalisability. Methods: We systematically applied a conceptual model of a trial sampling process to published literature from systematic review and prospective cross-sectional data. The eligibility criteria reported and used to exclude patients were classified by consensus as related to safety, internal validity, feasibility, or a combination thereof. Categorical data were reported as counts/proportions and continuous data were reported as median (IQR). Results: Thirty trials (n=1,638 participants) were included in the published literature and 1,013 patients in the prospective dataset. Thirty-seven per cent of trials did not describe their target population in the aim and conclusion, and 80% did not report all trial screening data. Eligibility criteria related to internal validity were the most common type reported and applied to exclude patients across both datasets. In the prospective dataset, 70% of patients were excluded for more than one reason. Conclusion: Key information to support the generalisability of trial findings was insufficiently reported in published upper limb motor research conducted early post-stroke. Broadening eligibility criteria alone is unlikely to sufficiently improve trial inclusivity due to internal validity constraints. Trials could achieve inclusivity through targeting multiple subpopulations, that in combination, produce clinically relevant results that are applicable to a broader population.

Despite an increase in the amount of published stroke recovery research, interventions have failed to markedly affect the trajectory of recovery poststroke. We argue that early-phase research to systematically investigate dose is an important contributor to advance the science underpinning stroke recovery. In this article, we aim to ( a) define the problem of insufficient use of a systematic approach to early-phase, multidimensional dose articulation research and ( b) propose a solution that applies this approach to design a multidimensional phase I trial to identify the maximum tolerated dose (MTD). We put forward a design template as a decision support tool to increase knowledge of how to develop a phase I dose-ranging trial for nonpharmaceutical stroke recovery interventions. This solution has the potential to advance the development of efficacious stroke recovery interventions, which include activity-based rehabilitation interventions.