Posts Tagged stratification
[ARTICLE] Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable – Full Text
In practical terms, biomarkers should improve our ability to predict long-term outcomes after stroke across multiple domains. This is beneficial for: (a) patients, caregivers and clinicians; (b) planning subsequent clinical pathways and goal setting; and (c) identifying whom and when to target, and in some instances at which dose, with interventions for promoting stroke recovery.2 This last point is particularly important as methods for accurate prediction of long-term outcome would allow clinical trials of restorative and rehabilitation interventions to be stratified based on the potential for neurobiological recovery in a way that is currently not possible when trials are performed in the absence of valid biomarkers. Unpredictable outcomes after stroke, particularly in those who present with the most severe impairment3 mean that clinical trials of rehabilitation interventions need hundreds of patients to be appropriately powered. Use of biomarkers would allow incorporation of accurate information about the underlying impairment, and thus the size of these intervention trials could be considerably reduced,4 with obvious benefits. These principles are no different in the context of stroke recovery as compared to general medical research.5
Interventions fall into two broad mechanistic categories: (1) behavioural interventions that take advantage of experience and learning-dependent plasticity (e.g. motor, sensory, cognitive, and speech and language therapy), and (2) treatments that enhance the potential for experience and learning-dependent plasticity to maximise the effects of behavioural interventions (e.g. pharmacotherapy or non-invasive brain stimulation).6 To identify in whom and when to intervene, we need biomarkers that reflect the underlying biological mechanisms being targeted therapeutically.
Our goal is to provide a consensus statement regarding the evidence for SRBs that are helpful in outcome prediction and therefore identifying subgroups for stratification to be used in trials.7 We focused on SRBs that can investigate the structure or function of the brain (Table 1). Four functional domains (motor, somatosensation, cognition, and language (Table 2)) were considered according to recovery phase post stroke (hyperacute: <24 h; acute: 1 to 7 days; early subacute: 1 week to 3 months; late subacute: 3 months to 6 months; chronic: > 6 months8). For each functional domain, we provide recommendations for biomarkers that either are: (1) ready to guide stratification of subgroups of patients for clinical trials and/or to predict outcome, or (2) are a developmental priority (Table 3). Finally, we provide an example of how inclusion of a clinical trial-ready biomarker might have benefitted a recent phase III trial. As there is generally limited evidence at this time for blood or genetic biomarkers, we do not discuss these, but recommend they are a developmental priority.9–12 We also recognize that many other functional domains exist, but focus here on the four that have the most developed science. […]
Continue —> Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation RoundtableInternational Journal of Stroke – Lara A Boyd, Kathryn S Hayward, Nick S Ward, Cathy M Stinear, Charlotte Rosso, Rebecca J Fisher, Alexandre R Carter, Alex P Leff, David A Copland, Leeanne M Carey, Leonardo G Cohen, D Michele Basso, Jane M Maguire, Steven C Cramer, 2017
Background. Neurological deficits after a stroke are commonly classified according to motor function for clinical decision making regarding discharge and rehabilitation. Participants in clinical stroke studies are also stratified by motor function to avoid a sampling bias.
Objective. This post hoc analysis examined a suite of upper limb functional assessment tools to test the hypothesis that motor function of survivors of stroke can be stratified using 2 simple tests of manual dexterity despite the heterogeneity of the population.
Methods. The functional ability of the more affected hand and arm was assessed for 67 hemiparetic patients, aged 18 to 83 years (mean ± standard deviation, 59.8 ± 14.0 years), at 1 to 264 months after a stroke (23.6 ± 39.6 months) using the Wolf Motor Function Test (WMFT), upper limb motor Fugl-Meyer Assessment (F-M), Box and Block Test (BBT), grooved pegboard test, and wrist range of motion. We tested the strength of our proposed stratification scheme with a hypothesis-driven hierarchical cluster analysis using standardized raw scores and dichotomous BBT and grooved pegboard test values.
Results. The most salient discriminator between low and higher motor function was the ability to move >1 block on the BBT. Within the higher function group, the ability to place all 25 pegs on the grooved pegboard test discriminated between moderate and high motor function. The derived scheme was congruent with clinical observations. The WMFT timed tasks, F-M scores, and range of motion did not discriminate functional groups.
Conclusions. Two simple unambiguous and objective tests of gross (BBT) and fine (grooved pegboard test) manual dexterity discriminated 3 groups of motor function ability for a heterogeneous group of patients after stroke.