PRE-APPLICATION WEBINAR

August 12, 20151:00-2:30 PM EDT

Collaborative Networks to Advance Delirium Research

RFA-AG-16-009 (R24)

Division of Neuroscience Dr. Molly Wagster

Division of Geriatrics and Clinical GerontologyDr. Susan ZiemanDr. Basil Eldadah

Scientific Review BranchDr. Jeanette Johnson

Hosts

Welcome

BackgroundOverview of the RFATimeline and ResourcesApplicant Questions

Verbal - use hand-raise button Written – send a chat message to Host

*Recorded for internal purposes only

Agenda

Very common- increasing as more seniors undergoing surgery and succumb to acute illness

Under-recognized and diagnosedLack of standardized diagnostic criteria, Diagnostic challenges: multiple phenotypes, episodicPatients under care of multiple providers/disciplinesMultiple underlying, superimposed, environmental risk factors

Associated with additional morbidity, mortality, cognitive and functional decline, loss of independence, prolonged hospitalization – particular vulnerability with underlying dementia

Very costly to individual and healthcare systemAt least 30-40% preventable, can be reversible

Background: Magnitude and Sequelae of Delirium

Advances in risk factor identification, rapid assessment tools and multifaceted prevention strategies

Progress in neuroimaging, potential role of neuroimmunology, chronic inflammation, genetics/-omics and underlying ties with dementia.

American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older (2014)

IOM Cognitive Aging: Progress in Understanding and Opportunities for Action (2015)Take steps to avoid the risk of cognitive changes due to delirium if

hospitalized.During and after hospital stays and post-surgery, health care

providers, patients and families should be alert to potential cognitive changes and delirium.

www/iom.edu/cognitiveagingAGS-NIA Conference: “Delirium in Older Adults: Finding Order in the

Disorder” 2/2014

Groundswell of Recent Delirium Activities

Goals: convene multidisciplinary leaders in delirium research to present state of field, identify research gaps and propose concepts to advance understanding of underlying mechanisms, diagnosis, management, prevention and outcomes of delirium.

February 2014, BethesdaParticipants

Neurologists, Geriatricians, Intensivists, Anesthesiologists, Neuroradiologists, Basic Scientists, Immunologists, Nursing, Surgeons, Psychologists, Hospitalists

Representatives from NIA, NINDS, NHLBI, and NIMHSummary of Delirium Conference: J Am Geriatr Soc 63:843–

852, 2015.

NIA-AGS Conference: “Delirium in Older Adults: Finding Order in the Disorder”

J Am Geriatr Soc 63:843–852, 2015.

Delirium is a common, costly and morbid condition primarily impacting older adults remains vastly under-recognizedvarious phenotypes and lack of standardized diagnostic

criteriaepisodic, logistical challenges

Current multi-pronged interventions improve a minority of patients;

The basic pathophysiology of delirium is poorly understood, but recent efforts in specialized fields, such as immunology, neuroimaging, and geriatrics, may lead to improved prevention, diagnosis and treatment;

NIA-AGS Delirium Conference Insights (1)

J Am Geriatr Soc 63:843–852, 2015.

Delirium is a truly multidisciplinary condition uniting specialists who do not frequently interact;

Despite advances, clinical progress appears to be somewhat slow, investigators focused on various aspects (mechanistic, prevention, diagnosis, intervention)

Delirium research could be markedly accelerated by creation of a research network/collaboratory which could unify the resources, expertise, and effort of these specialists

NIA-AGS Delirium Conference Insights (2)

J Am Geriatr Soc 63:843–852, 2015.

Delirium interface with other geriatric syndromesVoiding and sleep disorders, frailtyUnderlying pathophysiology? Risk factors? Specialized/targeted

interventions?Delirium pathophysiology and basic mechanisms

Roles of stress physiology, psychoneuroimmunology, neuroinflammation and neurotransmitter dysregulation

Delirium phenomenologySimilar are various etiologies, standardized diagnostic criteria,

prognosis, relationship with underlying dementia

NIA-AGS Delirium Conference: Some Specific Research Gaps (1)

J Am Geriatr Soc 63:843–852, 2015.

Delirium biomarkers and interaction with and/or distinguishing from underlying cognitive impairmentBiospecimens (blood, CSF, urine), genetics/-omics,

cellular/molecular measures, psychometric/cognitive testing, EEG, imaging, prognosis

Delirium and cognitive sequelaShort and long term cognitive impairment, interaction with

Alzheimer’s diseaseClinical and Intervention Studies for Delirium

Identification of risk factors, elucidation of phenotypes, prognostic indicators

Multicomponent, environmental, therapeutic, behavioral/ cognitive, prevention, prehabilitation, rehabilitation, phenotype specific?, measurement and quality control for clinical trials

NIA-AGS Delirium Conference: Some Specific Research Gaps (2)

To create an infrastructure for multi-faceted, transdisciplinary delirium research

To encourage collaboration between research and clinical disciplines focusing on delirium to advance knowledge of mechanisms, to develop or test prevention/treatment strategies

To create a training platform for early career investigators focusing on delirium research in older adults

To synergize delirium research efforts towards common goal of improving mechanistic understanding, prevention, detection, treatment and outcomes of delirium in older adults.

Goals of RFA-AG-16-009

To provide resources to research projects or to enhance research infrastructure

The infrastructure created should be greater than the sum of its components

May be single or multiple institutionsTransdisciplinary and/or multifaceted research emphasizedA variety of innovative research types may be proposed:

Basic research on mechanisms • NeuroimagingGenomics • Epidemiologic studiesEconomic impact • Health care

strategiesCreation of a biospecimen repositoryDevelopment and testing of diagnostic tools or interventions

R24 Resource-Building Opportunity

Ideally multidisciplinary with necessary clinical and research skills, focus, resources, commitment of effort, and operational effectiveness

Examples of investigators include (but not limited to) neuroscientists, immunologists, biomarker specialists, epidemiologists, biostatisticians, clinical trialists, neurologists, geriatricians, intensivists, surgeons, nurses, anesthesiologists, physical/occupational therapists, and social workers

Plans for leadership, networking, facilitating collaboration and communication, mentoring and training are encouraged

Industry or private sector organizations collaborators who bring specific expertise, skills and/or resources from are welcome

Foreign collaborators with specific expertise are welcome but applications must be submitted from a U.S.-based Institution

Investigators

Designed to leverage resources, investigative skills, database(s), clinical trial platform, networking/ collaboration/training to facilitate current and future advances in field

Application submitted from a single institutionCollaborating sites by institutional subcontract(s)

Specific plan for leadership, communication, resource and data sharing, dissemination of findings, future goals

May involve ‘cores’ of expertise

Organization of Infrastructure

Harmonize measures of delirium and related data elements across studies

Establish a common shared resource for data, biospecimens, imaging, etc.

Support pilot studies of basic mechanisms, development of animal models, testing of interventional approaches

Provide research opportunities for development of junior faculty

Meetings to prioritize research efforts and plan specific network activities

Information dissemination

Examples of Specific Delirium Network Activities

Creation of a collaborative research infrastructure that will continue beyond the 5-year funding periodFuture projects would be funded by investigator-initiated

awardsTraining arena for early career researchers and clinician-

scientistsSynergy of components should facilitate delirium

research advances at a more efficient rate than the efforts of individual research projects

Ideal Project Outcomes

Annual total costs are limited to $750,000Application budgets are limited to $500,000 in annual

direct costsProject duration is limited to 5 yearsNIA intends to issue one awardR24 award is not renewableFacilities & administration (F&A) rate

Use standard research rate If investigators have negotiated an alternate rate with their

institution, provide documentation in the application

Budget

RFA Published: May 27, 2015Letter of Intent Due: December 12, 2015Application Deadline: January 12, 2016Peer Review: July 2016

Special Emphasis PanelAdvisory Council Review: August 2016Earliest Funding Start Date: September 2016

RFA-AG-16-009 Timeline

RFA-AG-16-009 “Collaborative Networks to Advance Delirium Research (R24)”

RFA-AG-16-009 Pre-Application WebsiteWill include posting of these slides and responses to

Frequently Asked Questions Information pertaining to RFA-AG-16-009 will be posted at

on this siteNIA-AGS Delirium Research Conference Summary

J Am Geriatr Soc 63:843–852, 2015Please email your questions to: NIADeliriumNetwork@mail.nih.gov

Applicant Resources

Verbal and written questions welcomeDon’t need to use raise hand function Written questions can directed to hosts or entire group

FAQ will be added to Pre-Application Webinar Site after this webinar

Application Questions?