The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community\'s understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials\' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration.

OBJECTIVE: This study describes the process of updating the cerebral palsy (CP) common data elements (CDEs), specifically identifying tools that capture the impact of chronic pain on children\'s functioning.
METHODS: Through a partnership between the American Academy for Cerebral Palsy and Developmental Medicine and the National Institute of Neurological Disorders and Stroke (NINDS), the CP CDEs were developed as data standards for clinical research in neuroscience. Chronic pain was underrepresented in the NINDS CP CDEs version 1.0. A multi-step methodology was applied by an interdisciplinary professional team. Following an adapted CP chronic pain tools\' rating system, and a review of psychometric properties, clinical utility, and compliance with inclusion/exclusion criteria, a set of recommended pain tools was posted online for external public comment in May 2022.
RESULTS: Fifteen chronic pain tools met inclusion criteria, representing constructs across all components of the International Classification of Functioning, Disability and Health.
CONCLUSIONS: This paper describes the first condition-specific pain CDEs for a pediatric population. The proposed set of chronic pain tools complement and enhance the applicability of the existing pediatric CP CDEs. The novel CP CDE pain tools harmonize the assessment of chronic pain, addressing not only intensity of chronic pain, but also the functional impact of experiencing it in everyday activities.

A National Institute of Neurological Disorders and Stroke working group developed the Determinants of Inequities in Neurological Disease, Health, and Well-being framework. Our goal was to guide and inspire a new generation of neurologic research that pushes the field to design and test new approaches in pursuit of health equity, population health, and social justice. We seek to expand the lens of those looking to reduce or eliminate racial, socioeconomic status, and other inequities in neurologic disease, health, and well-being to improve our collective ability to create research, programs, and policies that lead to larger, more impactful, and more sustainable change in neurologic disease patterns. In this context, we outline a framework that includes and highlights \"upstream\" factors in the hopes of enhancing the focus of research, programmatic, and policy efforts to reduce and eliminate inequities in neurologic health and well-being. We explicitly discuss racism and other structural factors to clarify that social determinants are not natural and unchangeable. Populations with a disproportionate burden of neurologic disease are not inherently deficient, despite what some approaches to framing health inequities imply. The framework is presented linearly, but the pathways linking the determinants of neurologic disease, health, and well-being are far more complex than those demonstrated by the arrows included in the figure. The framework highlights the different levels and scale of causation, including the structural and intermediary social determinants and their impact on neurologic health. We offer this framework to refine efforts to contextualize the interpretation of neurologic research findings and suggest new avenues for their application. We illustrate how behavioral and biological factors occur in a social and economic context, factors that have been understudied as points of intervention to reduce inequities in neurologic disease. Considering social and structural determinants of health provides promising new opportunities to achieve neurologic health equity, reach social justice, and improve our science. Extending our work in this fashion is not simply about health equity or social justice but to fundamentally improve the quality of neurologic research by enhancing underlying theory and improving study design and implementation.

In 2020, the National Institute of Neurological Disorders and Stroke (NINDS) leadership asked its Advisory Council to review NINDS efforts in the domains of diversity, equity, inclusion, and health inequities. Part of these efforts involved a focus on health equity training and health equity research workforce diversification activities. The objective of this article was to summarize the findings and make recommendations regarding these training activities.
A subgroup of the National Advisory Neurological Disorders and Stroke Council Working Group for Health Disparities and Inequities in Neurological Disorders was engaged to advise NINDS leadership in the domain of diversity in health equity training. Activities included video teleconference meetings, multiple consultations with experienced leaders in the field, independent writing assignments, and an open public discussion as part of the NINDS HEADWAY workshop held on September 22-24, 2021.
The working group recommends support for 2 distinct types of training activities: one designed for scientists from historically under-represented backgrounds and the second designed for scientists of all backgrounds performing health inequities research. Support for grant writing workshops and establishment of multi-institutional mentorship networks are recommended as potentially especially high-yield activities. The working group recommends that all NINDS-supported investigators should have sufficient diversity, equity, and inclusion training to be prepared and qualified to mentor trainees from under-represented backgrounds and mentor trainees engaged in health disparities research; there should be no \"diversity tax\" placed on established investigators from under-represented backgrounds to shoulder all the mentorship responsibilities. Among other recommendations, training in health disparities research should include a focus on interventional studies to alleviate inequities as well as social science and qualitative methods.
There is a great deal of work to do in the field of diversity, equity, inclusion, and health inequities training, but we are optimistic that the activities outlined here, if fully implemented, will set us on the right track.

As detailed throughout this special issue, the National Institute of Neurological Disorders and Stroke (NINDS) recently undertook a strategic planning effort to guide the Institute\'s efforts and priorities in health disparities and health equity (HD/HE) research. One input into this effort was to conduct a 5-year longitudinal, in-depth analysis of NINDS-supported HD/HE research newly funded between the years 2016 and 2020. The goals of this analysis were to describe NINDS\'s portfolio according to consistent, contemporary definitions and HD/HE disciplinary theory. This required the development of a novel, systematic, and validated analysis protocol. The portfolio analysis was designed to inform the recommendations of an expert working group convened by the NINDS and internal efforts to support high-priority research, training, and infrastructure efforts.
NINDS staff developed and validated this HD/HE research portfolio analysis protocol. Ultimately, HD/HE projects were characterized by their disease focus, populations of study, the health equity determinant(s) addressed, and the type and phase of research being conducted. For all interventional research, there was further assessment of the type and setting of intervention delivery as well as utilization of evidence-based community engagement and intervention sustainability approaches.
A total of 58 new HD/HE research projects were funded from 2016 to 2020. The results of the descriptive analysis described here help provide a holistic picture of NINDS\'s HD/HE research portfolio, revealing strengths and gaps in the portfolio as well as opportunities ripe for future investment.
NINDS developed a standardized HD/HE research categorization methodology with imbedded quality control checks that is intended to be transparent, accurate, and reproducible. The results of this HD/HE research portfolio analysis will serve as a baseline from which to assess the success of NINDS\'s research investments going forward.

From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation. This article reviews the randomization designs for 3 trials currently enrolling in Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the SATURN (Statins in Intracerebral Hemorrhage Trial), the MOST (Multiarm Optimization of Stroke Thrombolysis Trial), and the FASTEST (Recombinant Factor VIIa for Hemorrhagic Stroke Trial). Randomization methods utilized in these trials include minimal sufficient balance, block urn design, big stick design, and step-forward randomization. Their advantages and limitations are reviewed and compared with traditional stratified permuted block design and minimization.

This proceedings article presents the scope of pediatric coma and disorders of consciousness based on presentations and discussions at the First Pediatric Disorders of Consciousness Care and Research symposium held on September 14th, 2021. Herein we review the current state of pediatric coma care and research opportunities as well as shared experiences from seasoned researchers and clinicians. Salient current challenges and opportunities in pediatric and neonatal coma care and research were identified through the contributions of the presenters, who were Jose I. Suarez, MD, Nina F. Schor, MD, PhD, Beth S. Slomine, PhD Erika Molteni, PhD, and Jan-Marino Ramirez, PhD, and moderated by Varina L. Boerwinkle, MD, with overview by Mark Wainwright, MD, and subsequent audience discussion. The program, executively planned by Varina L. Boerwinkle, MD, Mark Wainwright, MD, and Michelle Elena Schober, MD, drove the identification and development of priorities for the pediatric neurocritical care community.

At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of the NIH, completed an 18-month-long strategic planning process that involved and engaged diverse internal and external biomedical and general stakeholders. The institute published and disseminated its 2021-2026 Strategic Plan online in December 2020. Now, 1 year into its implementation, this progress report presents accomplishments to date, new initiatives and opportunities, and a preview of the metrics and benchmarks we will use to gauge the future progress of the strategic plan\'s implementation.

In the neurosciences, significant opportunities for sharing individual-level data are underexploited. Commentators suggest various barriers to data sharing, which may need to be addressed. Investigators\' perspectives on the main barriers are unclear. Furthermore, bioethicists have raised concerns about the potential misuse of neuroscience data, although discussions are hampered by uncertainty about the potential risks. It is unclear how common sensitive data are obtained and whether investigators judge them as sensitive.
An online survey was disseminated among 1,190 principal investigators (PIs) of active National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, or NIH Brain Research Through Advancing Innovative Neurotechnologies Initiative grants involving human subject research.
A total of 397 investigators responded to the survey (response rate 33%). Most investigators (84%) support efforts to increase sharing of deidentified individual-level data. However, investigators perceive many barriers to data sharing. The largest barriers were costs and time; limited interpretation of the data without understanding the context of data collection; lack of incentives; limited standardization and norms for data acquisition, formatting, and description; and heterogeneity of data types. Several types of data described as sensitive in the literature are common among neuroscience studies, for example, neural correlates of behavior, emotions, or decision making (71%) and/or predictive data (54%). Although most investigators consider it unlikely or extremely unlikely for their research data to be misused to harm individual research participants (82%), the majority were at least slightly concerned about potential harm to individuals if their research data were misused (65%). Investigators with more easily reidentifiable data, data from vulnerable groups, and neural data were more concerned about the likelihood of misuse and/or magnitude of harm of misuse of their research data.
We hope these data help prioritize the development of tools and strategies to overcome the main barriers to data sharing. Furthermore, these data provide input on what may be sensitive data for which additional safeguards should be considered.

The NINDS rt-PA Stroke Study is frequently cited in support of alteplase for acute ischemic stroke within 3 h of symptom onset. Multiple post-hoc reanalyses of this trial have been published to adjust for a baseline imbalance in stroke severity. We performed a risk of selection bias assessment and reanalyzed trial data to determine if the etiology of this baseline imbalance was more likely due to random chance or randomization errors.
A risk of selection bias assessment was conducted using signaling questions from the Cochrane Risk of Bias 2 (ROB 2) tool. Four sensitivity analyses were conducted on the trial data based on the randomization process: assessment of imbalances in allocation in unique strata; adherence to a pre-specified restriction on randomization between time strata at each randomization center; assessment of differences in baseline computed tomography (CT) results in unique strata; and comparison of baseline characteristics between allocation groups within each time strata. A multivariable logistic regression model was used to compare reported treatment effects with revised treatment effects after adjustment of baseline imbalances identified in the sensitivity analyses.
Based on criteria from the ROB 2 tool, the risk of bias arising from the randomization process was high. Sensitivity analyses found 11 of 16 unique strata deviated from the expected 1:1 allocation ratio. Three randomization centers violated an apriori rule regarding a maximum difference in allocation between the time strata. Three unique strata had imbalances in baseline CT results that prognostically favored alteplase. Four imbalances in baseline characteristics were identified in the 91-180-min time stratum that all prognostically favored alteplase and were consistent with a larger alteplase treatment effect size compared to the 0-90-min time stratum. After adjustments for baseline imbalances, all reported treatment effects were reduced. Three out of seven originally positive reported results were revised to non-significant.
This risk of selection bias assessment revealed a high risk of selection bias in the NINDS rt-PA Stroke Study. Sensitivity analyses conducted based on the randomization process supported this assessment. Baseline imbalances in the trial were more likely due to randomization errors than random chance. Adjusted analyses accounting for baseline imbalances revealed a reduction in reported treatment effects supporting the presence of selection bias in the trial. Treatment decisions and guideline recommendations based on the original treatment effect reported in the NINDS rt-PA Stroke Study should be done cautiously.