The NINDS 2021-2026 Strategic Plan: Partnership and cross-cutting principles.

The 2021-2026 Strategic Plan of the National Institute of Neurological Disorders and Stroke began with a vision, a mission, and strategic objectives elaborated from within the institute. This plan is a collaborative product of the institute and its many stakeholders, emphasizing cross-cutting operational principles including scientific rigor, communication, workforce culture, and equity.

Cerebral palsy pain instruments: Recommended tools for clinical research studies by the National Institute of Neurological Disorders and Stroke Cerebral Palsy Common Data Elements project.

AIM: 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. METHOD: 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. INTERPRETATION: 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.

Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

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.

Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience.

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.

Proceedings of the First Pediatric Coma and Disorders of Consciousness Symposium by the Curing Coma Campaign, Pediatric Neurocritical Care Research Group, and NINDS: Gearing for Success in Coma Advancements for Children and Neonates.

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.

Health Equity and Actionable Disparities in Stroke: 2021 Update.

There are stark inequities in stroke incidence, prevalence, acute care, rehabilitation, risk factor control, and outcomes. To address these inequities, it is critical to engage communities in identifying priorities and designing, implementing, and disseminating interventions. This issue of Stroke features health equity themed lectures delivered during the International Stroke Conference and Health Equity and Actionable Disparities in Stroke: Understanding and Problem-Solving meetings in 2021 as well as articles covering issues of disparities and diversity in stroke. Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, received the 2021 William Feinberg Award Lecture for his lifetime achievements in seeking global and local solutions to cerebrovascular health inequities. The second annual Health Equity and Actionable Disparities in Stroke: Understanding and Problem-Solving symposium, which took place the day before the International Stroke Conference in February 2021, focused on community-engaged research for reducing inequities in stroke. Phil Gorelick, MD was awarded the Edgar J. Kenton III Award for his lifetime achievements in using community engagement strategies to recruit and retain Black participants in observational studies and clinical trials. Walter Koroshetz, MD, Director of the National Institute of Neurological Disorders and Stroke delivered the keynote lecture on stroke inequities and Richard Benson, MD, PhD, Director of the Office of Global Health and Health Disparities at National Institute of Neurological Disorders and Stroke, gave a lecture focused on National Institute of Neurological Disorders and Stroke efforts to address inequities. Nichols et al highlighted approaches of community-based participatory research to address stroke inequities. Verma et al showcased digital health innovations to reduce inequities in stroke. Das et al showed that the proportion of underrepresented in medicine vascular neurology fellows has lowered over the past decade and authors provided a road map for enhancing the diversity in vascular neurology. Clearly, to overcome inequities, multipronged strategies are required, from broadening representation among vascular neurology faculty to partnering with communities to conduct research with meaningful impact.

The National Institute of Neurological Disorders and Stroke's efforts on diversifying the neuroscience research workforce.

Research innovation that leads to discovery in the battle against neurological disease and disorders requires diverse ideas. The National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health's 27 institutes and centers, strives to reduce the burden of neurological disease and disorders. The National Institutes of Neurologic Disorders and Stroke is very interested in increasing the diversity of researchers by addressing the existing barriers responsible for the low numbers of underrepresented populations from traditionally minority-serving institutions (MSIs) and non-minority serving institutions (non-MSIs). This commentary provides insight on the persistent underrepresentation of racial/ethnic minorities entering neuroscience research careers paths, focusing on multiples levels within the scientific academy and the supportive role that both MSIs and non-MSIs play in increasing diversity in the biomedical research workforce.

Risk of selection bias assessment in the NINDS rt-PA stroke study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Common data elements to standardize genomics studies in cerebral palsy.

AIM: To define clinical common data elements (CDEs) and a mandatory minimum data set (MDS) for genomic studies of cerebral palsy (CP). METHOD: Candidate data elements were collated following a review of the literature and existing CDEs. An online, three-round Delphi survey was used to rate each data element as either 'core', 'recommended', 'exploratory', or 'not required'. Members of the International Cerebral Palsy Genomics Consortium (ICPGC) rated the core CDEs as either mandatory or not, to form the MDS. For both the CDEs and the MDS, a data element was considered to have reached consensus if more than 75% of respondents agreed. RESULTS: Forty-six individuals from around the world formed the Delphi panel: consumers (n=2), scientists/researchers (n=17), medical (n=19), and allied health professionals (n=8). The CDEs include 107 data elements across six categories: demographics, diagnostics, family history, antenatal and neonatal details, clinical traits, and CP-specific assessments. Of these, 10 are mandatory, 42 core, 41 recommended, and 14 are exploratory. INTERPRETATION: The ICPGC CDEs provide a foundation for the standardization of phenotype data captured in CP genomic studies and will benefit international collaborations and pooling of data, particularly in rare conditions. WHAT THIS PAPER ADDS: A set of 107 common data elements (CDEs) for genomics studies in cerebral palsy is provided. The CDEs include standard definitions and data values domains. The CDEs will facilitate international data sharing, collaboration, and improved clinical interpretation of findings.

OBJETIVO: Definir elementos de dados clínicos comuns (DCC) e um conjunto mínimo de dados obrigatórios (CMDO) para estudos genômicos de paralisia cerebral (PC). MÉTODO: Os elementos de dados do candidato foram coletados seguindo uma revisão da literatura e através dos DCC existentes. Uma pesquisa on-line de três rodadas Delphi foi usada para classificar cada elemento de dados como 'essencial', 'recomendado', 'exploratório' ou 'não obrigatório'. Os Membros do Consorcio Internacional de Genoma na Paralisia Cerebral (MCIGPC) classificaram os DCC do núcleo como obrigatórios ou não, para formar o CMDO. Tanto para os DCC quanto para o CMDO, um elemento de dados foi considerado como tendo chegado a um consenso se mais de 75% dos respondentes concordassem. RESULTADOS: Quarenta e seis indivíduos de todo o mundo formaram o painel Delphi: consumidores (n=2), cientistas/pesquisadores (n=17), médicos (n=19) e profissionais de saúde aliados (n=8). Os DCC incluem 107 elementos de dados em seis categorias: demografia, diagnóstico, história familiar, detalhes pré-natais e neonatais, características clínicas e avaliações específicas de PC. Destes, 10 são obrigatórios, 42 essenciais, 41 recomendados e 14 são exploratórios INTERPRETAÇÃO: Os DCC do MCIGPC fornecem uma base para a padronização de dados de fenótipo capturados em estudos genômicos de PC e beneficiarão colaborações internacionais e agrupamento de dados, particularmente em condições raras.

Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program.

OBJECTIVE: Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic-clonic seizures that can continue throughout life. To facilitate the development of ASDs for DS, the contract site of the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) has evaluated a mouse model of DS using the conditional knock-in Scn1aA1783V/WT mouse. METHODS: Survival rates and temperature thresholds for Scn1aA1783V/WT were determined. Prototype ASDs were administered via intraperitoneal injections at the time-to-peak effect, which was previously determined, prior to the induction of hyperthermia-induced seizures. ASDs were considered effective if they significantly increased the temperature at which Scn1aA1783V/WT mice had seizures. RESULTS: Approximately 50% of Scn1aA1783V/WT survive to adulthood and all have hyperthermia-induced seizures. The results suggest that hyperthermia-induced seizures in this model of DS are highly refractory to a battery of ASDs. Exceptions were clobazam, tiagabine, levetiracetam, and the combination of clobazam and valproic acid with add-on stiripentol, which elevated seizure thresholds. SIGNIFICANCE: Overall, the data demonstrate that the proposed model for DS is suitable for screening novel compounds for the ability to block hyperthermia-induced seizures and that heterozygous mice can be evaluated repeatedly over the course of several weeks, allowing for higher throughput screening.

HEADS-UP: Understanding and Problem-Solving: Seeking Hands-Down Solutions to Major Inequities in Stroke.

There are substantial and longstanding inequities in stroke incidence, prevalence, care, and outcomes. The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-Solving (HEADS-UP) symposium is an annual multidisciplinary scientific and educational forum targeting major inequities in cerebrovascular disease, with the ultimate objective of helping to bridge major inequities in stroke, and promptly translating scientific results into routine clinical practice, for the benefit of vulnerable and underserved populations. HEADS-UP is a collaborative undertaking by the National Institute of Neurological Disorders and Stroke and the American Stroke Association and is held the day before the annual International Stroke Conference. In 2020, the HEADS-UP focused on the topic of racial/ethnic disparities in stroke and comprised invited lectures on determinants of racial/ethnic inequities in stroke as well as emerging interventions or promising strategies designed to overcome these inequities. Competitively selected travel award scholarships were given to 19 early stage investigators who presented posters at professor moderated sessions; engaged in several career development activities aimed imparting grant writing skills, knowledge about climbing the academic ladder, and striving for work-life balance; and participated in networking events. This Health Equity edition of Focused Updates will feature an overview of the HEADS-UP 2020 symposium proceedings and articles covering the key scientific content of the major lectures delivered during the symposium including the presentation by the award-winning plenary speaker. Starting in 2021, HEADS-UP will expand to include 5 major inequities in stroke (racial/ethnic, sex, geographic, socioeconomic, and global) and seeks to be a viable avenue to meet the health equity goals of the American Heart Association/American Stroke Association, National Institutes of Neurological Disorders and Stroke, and World Stroke Organization.

Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Alteplase Over Placebo.

Background and Purpose- The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods- We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score-24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score-24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95-100 and modified Rankin Scale score of 0-1), good 3-month functional outcome (modified Rankin Scale score of 0-2), and 3-month infarct volume. Results- There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P=0.045) but not median delta NIHSS (3 versus 2; P=0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROCpercent) was better than delta NIHSS (ROCdelta) and admission NIHSS (ROCadmission) with regards to excellent 3-month Barthel Index (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.75), excellent 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.74; ROCadmission, 0.78), and good 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.78). Conclusions- In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Clinical Conditions "Suggestive of Progressive Supranuclear Palsy"-Diagnostic Performance.

BACKGROUND: The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level "suggestive of progressive supranuclear palsy" for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. OBJECTIVE: To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. METHODS: Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. RESULTS: The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. CONCLUSIONS: Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Proceedings of the 15th Antiepileptic Drug and Device Trials Meeting: State of the Science.

On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from preclinical models to clinical prognostication. The conference featured regulatory agencies, academic laboratories, and healthcare companies involved in emerging epilepsy therapies and research. The program included discussions around funding and support for investigations in epilepsy and neurologic research, clinical trial design and integrated outcome measures for people with epilepsy, and drug development and upcoming disease-modifying therapies. Finally, the conference included updates from the preclinical, clinical, and device pipeline. Summaries of the talks are provided in this paper, with the various pipeline therapeutics in the listed tables to be outlined in a subsequent publication.

Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI): an overview of initial enrollment and demographics.

OBJECTIVE: Traumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI). METHODS: Data were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury. RESULTS: One hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed. CONCLUSIONS: The authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

Vascular contributions to cognitive impairment and dementia (VCID): A report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop.

Vascular contributions to cognitive impairment and dementia (VCID) are characterized by the aging neurovascular unit being confronted with and failing to cope with biological insults due to systemic and cerebral vascular disease, proteinopathy including Alzheimer's biology, metabolic disease, or immune response, resulting in cognitive decline. This report summarizes the discussion and recommendations from a working group convened by the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke to evaluate the state of the field in VCID research, identify research priorities, and foster collaborations. As discussed in this report, advances in understanding the biological mechanisms of VCID across the wide spectrum of pathologies, chronic systemic comorbidities, and other risk factors may lead to potential prevention and new treatment strategies to decrease the burden of dementia. Better understanding of the social determinants of health that affect risks for both vascular disease and VCID could provide insight into strategies to reduce racial and ethnic disparities in VCID.

Definition and Prioritization of Data Elements for Cohort Studies and Clinical Trials on Patients with Unruptured Intracranial Aneurysms: Proposal of a Multidisciplinary Research Group.

INTRODUCTION: Variability in usage and definition of data characteristics in previous cohort studies on unruptured intracranial aneurysms (UIA) complicated pooling and proper interpretation of these data. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke UIA and Subarachnoid Hemorrhage (SAH) Common Data Elements (CDE) Project was to provide a common structure for data collection in future research on UIA and SAH. METHODS: This paper describes the development and summarization of the recommendations of the working groups (WGs) on UIAs, which consisted of an international and multidisciplinary panel of cerebrovascular specialists on research and treatment of UIAs. Consensus recommendations were developed by review of previously published CDEs for other neurological diseases and the literature on UIAs. Recommendations for CDEs were classified by priority into 'Core,' 'Supplemental-Highly Recommended,' 'Supplemental,' and 'Exploratory.' RESULTS: Ninety-one CDEs were compiled; 69 were newly created and 22 were existing CDEs. The CDEs were assigned to eight subcategories and were classified as Core (8), Supplemental-Highly Recommended (23), Supplemental (25), and Exploratory (35) elements. Additionally, the WG developed and agreed on a classification for aneurysm morphology. CONCLUSION: The proposed CDEs have been distilled from a broad pool of characteristics, measures, or outcomes. The usage of these CDEs will facilitate pooling of data from cohort studies or clinical trials on patients with UIAs.

Common Data Elements for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage Clinical Research: A National Institute for Neurological Disorders and Stroke and National Library of Medicine Project.

OBJECTIVES: The goal for this project was to develop a comprehensive set of common data elements (CDEs), data definitions, case report forms and guidelines for use in unruptured intracranial aneurysm (UIA) and subarachnoid hemorrhage (SAH) clinical research, as part of a new joint effort between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Library of Medicine of the US National Institutes of Health. These UIA and SAH CDEs will join several other neurological disease-specific CDEs that have already been developed and are available for use by research investigators. METHODS: A Working Group (WG) divided into eight sub-groups and a Steering Committee comprised of international UIA and SAH experts reviewed existing NINDS CDEs and instruments, created new elements when needed and provided recommendations for UIA and SAH clinical research. The recommendations were compiled, internally reviewed by the entire UIA and SAH WG and posted online for 6 weeks for external public comments. The UIA and SAH WG and the NINDS CDE team reviewed the final version before posting the SAH Version 1.0 CDE recommendations. RESULTS: The NINDS UIA and SAH CDEs and supporting documents are publicly available on the NINDS CDE ( https://www.commondataelements.ninds.nih.gov/#page=Default ) and NIH Repository ( https://cde.nlm.nih.gov/home ) websites. The recommendations are organized into domains including Participant Characteristics and Outcomes and Endpoints. CONCLUSION: Dissemination and widespread use of CDEs can facilitate UIA and SAH clinical research and clinical trial design, data sharing, and analyses of observational retrospective and prospective data. It is vital to maintain an international and multidisciplinary collaboration to ensure that these CDEs are implemented and updated when new information becomes available.