American Recovery and Reinvestment Act of 2009

NIH Challenge Grants in Health and Science Research (RFA-OD-09-003)
National Institute of Neurological Disorders and Stroke

NIH has received new funds for Fiscal Years 2009 and 2010 as part of the American Recovery & Reinvestment Act of 2009 (Recovery Act), Pub. L. No. 111-5. The NIH has designated at least $200 million in FYs 2009 - 2010 for a new initiative called the NIH Challenge Grants in Health and Science Research.

This new program will support research on topic areas that address specific scientific and health research challenges in biomedical and behavioral research that would benefit from significant 2-year jumpstart funds.

The NIH has identified a range of Challenge Areas that focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways. Each NIH Institute, Center, and Office has selected specific Challenge Topics within the broad Challenge Areas related to its mission. The research in these Challenge Areas should have a high impact in biomedical or behavioral science and/or public health.

NIH anticipates funding 200 or more grants, each of up to $1 million in total costs, pending the number and quality of applications and availability of funds. In addition, Recovery Act funds allocated to NIH specifically for comparative effectiveness research (CER) may be available to support additional grants. Projects receiving these funds will need to meet this definition of CER: "a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients. Such a study may compare similar treatments, such as competing drugs, or it may analyze very different approaches, such as surgery and drug therapy." Such research may include the development and use of clinical registries, clinical data networks, and other forms of electronic health data that can be used to generate or obtain outcomes data as they apply to CER.

The application due date is April 27, 2009.

Broad Challenge Areas and Specific Challenge Topics

Note: Those marked with an asterisk (*) are the highest priority topics; however, applicants may apply to any of the topics.

For NINDS, the Challenge Topics are listed below:

Challenge Topics of the National Institute of Neurological Disorders and Stroke (NINDS)

NINDS Challenge Grant Topics

Broad Challenge Area	Specific Challenge Topic
(01) Behavior, Behavioral Change, and Prevention	01-NS-101 Limiting neurological disability through behavior change. Research on behavior change could advance the neurological health of patients at risk for, or affected by, a wide range of neurological disorders. The challenge is to test behavioral models that improve compliance with treatment regimens, stress reduction to attenuate neurologic symptoms, exercise regimens, accessing emergency care, or management of pseudo-seizures. Contact: Dr. Emmeline Edwards, 301-496-9248, ee48r@nih.gov
(02) Bioethics	02-OD(OSP)-101* Unique Ethical Issues Posed by Emerging Technologies. Advances in biotechnology and biomedical science raise novel ethical, legal, and social issues. Research in this area is needed to understand the unique ethical concerns related to emerging technologies (e.g. biotechnology, tissue engineering, nanomedicine, and synthetic biology). These include issues such as dual use research, privacy, safety, intellectual property, commercialization and conflict of interest, among others. Research is also needed to assess how these novel issues are addressed under current oversight and regulatory structures and identify where there may be gaps and/or need for revised or new oversight approaches. OD(OSP) Contact: Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NINDS Contact: Dr. Joe Pancrazio, 301-496-1447, jp439m@nih.gov 02-OD(OSP)-102* Ethical Issues in Health Disparities and Access to Participation in Research. Research is needed to assess the under-representation in biomedical and clinical research of U.S. minority populations, underserved populations, and populations who may be vulnerable to coercion or undue influence, to identify barriers to participation in research and to develop approaches for overcoming them. Additionally, studies are needed to assess the impact and ethical considerations of conducting biomedical and clinical research internationally in resource-limited countries. OD(OSP) Contact: Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NINDS Contact: Dr. Salina Waddy, 301-496-3102, Salina.Waddy@nih.gov 02-OD(OSP)-104* Ethical Issues in the Translation of Genetic Knowledge to Clinical Practice. Genetics and genomics have great promise for the development of personalized medicine, yet the ethical, legal and social implications of both the research and application of genetic and genomic knowledge and technology are far reaching. Studies are needed to better understand the factors that influence the translation of genetic information to improved human health and the associated ethical issues. Examples of studies include those to address ethical issues related to broad sharing and use of new genetic information and technologies for research to improve human health, human subjects protection in genetic and genomic research, the identifiability of genetic/genomic information and how our understanding of identifiability is evolving, return of research results and incidental findings to subjects, alternative models of informed consent for broad data sharing for research, and the impact of intellectual property (IP) issues on development of new technologies. OD(OSP) Contact: Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NINDS Contact: Dr. Danilo Tagle, 301-446-5748, dt39y@nih.gov 02-OD(OSP)-105* Ethical Issues Raised by the Blurring between Treatment and Research. The distinction between clinical practice and research is growing less clear, a trend that may be more pronounced with respect to genetic information and medical records research. Studies are needed to better understand the ethical issues associated with this trend. Examples of studies include those to identify how this blurring in roles affects traditional human subjects protections, including, for example, essential practices such as informed consent, conceptions of the doctor/patient and investigator/subject relationship, and privacy protections. OD(OSP) Contact: Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NINDS Contact: Dr. Brandy Fureman, 301-496-9135, bf103s@nih.gov
(03) Biomarker Discovery and Validation	03-NS-101* Identification and validation of biomarkers for Proof of Concept (early Phase IIa) studies for Nervous System Disorders. For many neurological disorders, moving potential therapies from promising studies in animal models to clinical trials that demonstrate effectiveness in patients remains a major hurdle. Identifying and validating biomarkers that associate with a beneficial response to treatment in the human (or in the animal model) which can also be measured in patients would help overcome this hurdle. These biomarkers could be used in Phase IIa Proof of Concept studies to determine whether a therapeutic intervention has engaged the intended biologic target. Contact: Dr. Ursula Utz, 301-496-1431, utzu@ninds.nih.gov. 03-NS-102 Standardization and validation of neurological biomarkers. There are many promising biomarkers for neurological disorders whose usefulness for research or health care is limited due to lack of standardization and/or multi-center validation of sensitivity and specificity. These include, for example, tests of mitochondrial dysfunction, identification of specific cell types in brain (stem cells, malignant cells, inflammatory cells, etc.), perfusion imaging in acute stroke, diffusion -based imaging in traumatic brain injury, and objective measures linked to the progressively disabling pathology in Parkinson's disease, multiple sclerosis, spinal muscular atrophy, and other neurological disorders. Contact: Dr. Ursula Utz, 301-496-1431, utzu@ninds.nih.gov.
(04) Clinical Research	04-NS-101 Constructing a relational database for neurological diseases. A dynamic, biologically clustered, publicly accessible, relational database of neurological diseases that reflects current scientific understanding would be highly valuable to the NINDS and the scientific and lay community. It could also serve to illustrate the "knowledge landscape" of specific neurological disorders and their interrelationships and help in analyzing scientific opportunities with respect to the current state of relevant research supported by NINDS as well as other Institutes, foundations, industry, and disease-related organizations. Contact: Dr. Yuan Liu; 301-496-0012, liuyuan@ninds.nih.gov 04-NS-102 Developing web-based entry and data-management tools for clinical research. The construction of open source, user-friendly, web-based data entry and data management tools that could be customized by investigators would serve as a core resource for the community. In addition, the inclusion of common data elements in such databases in collaboration with NINDS would greatly facilitate the ability to combine datasets, facilitate data sharing, and perform data mining among clinical research datasets and report trial results to clinicaltrials.gov. Contact: Joanne Odenkirchen; 301-496-3104, odenkirj@ninds.nih.gov 04-NS-103 Developing consortia for clinical research. Research progress in rare as well as common neurological disorders is often limited by the lack of a sizeable consortium with shared goals and ability to coalesce around a specific clinical research project. Applicants would have to demonstrate need and immediate impact by providing details on what research would be performed in the near future. Clinical protocols should be generated at the time of submission, but probably not yet IRB-reviewed/approved. Contact: Dr. Scott Janis, 301-496-9135, janiss@ninds.nih.gov
(05) Comparative Effectiveness Research	05-NS-101* Consortia Building for Comparative Effectiveness Research in Clinical Neuroscience. The development of evidence-based medicine to inform health decisions in neurology, neurosurgery and neurorehabilitation requires analysis of high quality, risk-stratified, data collection from "real world" practice. The challenge is to develop multi-center consortia that effectively utilize modern electronic data collection systems to standardize, collect and analyze high quality data in order to compare the effectiveness of alternative methods of prevention, diagnosis, or treatment in groups of patients with specific types/subtypes of neurological disorders. NINDS Contact: Dr. Walter J. Koroshetz, 301-496-3167, koroshetzw@ninds.nih.gov 05-NS-102* Technologies to Enable Comparative Effectiveness Research in Clinical Neuroscience High per patient costs limit the number of patients studied in RCTs as well as the rate at which important questions can be tested by RCTs. High per patient costs make it prohibitively expensive to study the comparative effectiveness of a treatment, prevention or diagnostic regimen as it transitions from clinical trial to the larger venue of clinical practice. The challenge is to develop new technologies that can obtain clinically significant outcomes in larger numbers of patients at lower cost. The performance characteristics of such technologies in providing high quality outcome measures could be tested by comparing to standard outcome measures in the context of an ongoing RCT. NINDS Contact: Dr. Walter J. Koroshetz, 301-496-3167, koroshetzw@ninds.nih.gov 05-NS-103* Validating NIH's New Clinical Tools in Populations With Neurological Disorders The NIH Blueprint for neuroscience is developing a variety of standardized tests in the domains of cognition, emotion, sensation, and motor function as part of the NIH Toolbox project. The NINDS is supporting the development of quality of life outcomes in neurological disorders. The NIH Roadmap project has developed the patient reported outcomes measurement information system (PROMIS). Each of these tools utilizes computerized adaptive testing methods to obtain important clinical outcome data and will be tested in large groups of normal individuals across the lifespan. The challenge is to assess the performance and research utility of these new tools in well described patient populations for future comparative effectiveness research projects. NINDS Contact: Dr. Claudia Moy, 301-496-2789, moyc@ninds.nih.gov 05-NS-104* Intervention vs. Best Medical Therapy in Asymptomatic Persons With Identified Vascular Abnormalities. A variety of vascular/cardiac abnormalities cause stroke but are treated by a surgical or endovascular intervention that itself carries risk of stroke and death, i.e. carotid stenosis, vertebral origin stenosis, berry aneurysm, arteriovenous malformation, cerebral artery dissection, patent foramen ovale, etc. In many of these conditions the risk of stroke due to the vascular abnormality is significantly lower in asymptomatic patients as compared to those who present with symptoms. Without a means to accurately stratify risk, such asymptomatic patients are faced with very difficult health decisions. The challenge to be completed over a two year period could include one or all of the following: 1) meta-analysis of existing datasets or registries (for example, Medicare, HMO, or Insurance company data to develop an evidence base for clinical-decision making. 2) pilot grants for an RCT, and 3) validation of selection criteria to stratify stroke risk in asymptomatic patients with defined anatomic abnormalities. NINDS Contact: Dr. Walter J. Koroshetz, 301-496-3167, koroshetzw@ninds.nih.gov
(06) Enabling Technologies	06-NS-101 Developing minimally invasive measures of neural activity. Research in the nervous system is often limited by the inability to access the critical pathology. Major neurobiological breakthroughs have come on the back of technological advances. New technologies that enable neuroscientists to study important, but previously unmeasurable, aspects of neural activity and anatomy, gene expression, metabolism, protein distribution, specific cell-type distribution, etc. could lead to quantum leaps in neuroscience. Contact: Dr. Randy Stewart, 301-496-1917, rs416y@nih.gov 06-NS-102 Minimally invasive diagnostic and treatment tools. Treatment and diagnosis of patients with neurological disorders is often limited by access to the neuro-pathology. Minimally invasive procedures that allow access to neuro-pathology for diagnostic, monitoring, or treatment with greater efficacy and decreased morbidity could significantly enhance neurological health. Contact: Dr. Joe Pancrazio, 301-496-1447, jp439m@nih.gov 06-NS-103 Breakthrough technologies for neuroscience. Advances in basic neuroscience are often catalyzed by the development of breakthrough technologies that allow interrogation of nervous system function (e.g. patch clamp recording from single cells, optical imaging, multi-channel recording arrays, fluorescent dyes to image cell types and intracellular processes, etc.). The challenge is to develop new technologies with the potential to enable basic neuroscientists to make future quantum leaps in understanding nervous system development and function. Contact: Dr. Edmund Talley, 301-496-1917, talleye@ninds.nih.gov 06-NS-104 Developing and validating assistive neuro-technologies. The burden of illness of neurological disorders could be reduced by enabling technologies that reduce functional disability in patients with severe motor or sensory loss. For example, these would include technologies that improve ambulation, upper extremity dexterity, swallowing, or neural control of prostheses. Contact: Dr. Naomi Kleitman, 301-496-1447, nk85q@nih.gov 06-NS-105 Importing important technologies into neuroscience. The challenge is to capitalize on existing knowledge and technologies from other scientific disciplines (e.g. applied physics, nanotechnology, cancer biology, and immunology) to catalyze progress in basic and clinical neuroscience (e.g. cell signaling or cell cycle control mechanisms in neurodegeneration, inflammation in neurological disease, epigenetics in neural development, etc.). Proposals will also be considered that seek to validate, in neurological systems, technologies originally developed for use in other biological systems. Contact: Dr. Joe Pancrazio, 301-496-1447, jp439m@nih.gov 06-NS-106 Validating new methods to study brain connectivity. More complete understanding of the structure and function of human brain networks will be critical for answering many longstanding questions in neuroscience research. Toward this end, applications are invited for research efforts that will contribute to or facilitate coordinated approaches to map mammalian brain connectivity, including research to develop experimental, analytical or computational tools and methods. Contact: Dr. Edmund Talley, 301-496-1917, talleye@ninds.nih.gov 06-NS-107 Sensors to monitor neurologic function. Clinical neuroscience research is often based on a small number of repeated assessments of neurological function, deterioration of which is associated with disease progression and functional disability. New sensor technologies that directly monitor and integrate patient function in real life, e.g. daily ambulation distance and speed, sway and falls, tremor, chorea, dysarthria, speech quality and output, sleep and drowsiness, absence seizures, would offer a completely new method of evaluating disease burden, response to therapeutic intervention, and adverse events. Contact: Dr. Debra Babcock and Dr. James Gnadt, 301-496-9964, dbabcock@ninds.nih.gov and gnadtjw@mail.nih.gov 06-AG-101* Neuroscience Blueprint: Development of non-invasive imaging approaches or technologies that directly assess neural activity. This could include research on imaging neuronal electrical currents, neurotransmitter changes and/or neuronal/glial cell responses to brain circuit activation. This scientific area could be advanced by improvements/refinements in existing imaging technology or use of emerging technology that could be developed in two years. The outcome of this challenge could have high impact by connecting the system-level, large population view afforded by fMRI with the cellular processes and responses that contribute to the BOLD-fMRI signal. Two-year challenge projects could stimulate the development of human brain imaging techniques that link cell activity underlying neural communication to the structure and function of brain circuits, and could complement other brain connectivity imaging modalities. NIA Contact: Dr. Bradley Wise, 301-496-9350, wiseb@nia.nih.gov; NINDS Contact: Contact: Dr. Randy Stewart, 301-496-1917, rs416y@nih.gov
(07) Enhancing Clinical Trials	07-NS-101* Developing technology to increase efficiency and decrease cost of clinical trials. Clinical trials are becoming increasingly expensive, and many US patients are unwilling to enroll, which has led to delays in trial completion and further cost increases. The challenge is to develop and test affordable, technologies to enable remote, centralized monitoring of physiologic, behavioral and neurologic indices as well as study medication compliance, and adverse effects in clinical trials. These technologies should provide opportunities to enhance efficiency in clinical trials, as well as to collect more "real life" data. Contact: Dr. Emmeline Edwards, 301-496-9248, ee48r@nih.gov
(08)Genomics	08-NS-101* Cross-disease research to identify mechanisms common to Mendelian disorders of low incidence and genetically complex, high incidence disorders. Progress in treating many common neurological and neurobehavioral disorders has been hindered by the complex genetics and heterogeneous etiologies of these disorders. However, analyzing related or clinically overlapping Mendelian disorders or studying rare genetic variants of large effect can yield unique biological insight into the mechanisms underlying common disease. This challenge encourages studies that dissect pathways common to simple and complex genetic disorders, with the goal of identifying potential therapeutic targets. Contact: Dr. Jane Fountain, 301-496-1431, fountai@ninds.nih.gov
(09) Health Disparities	09-NS-101 Improving representation of African American, Hispanic Americans and Native Americans in clinical research. Current data indicate that African Americans, Native Americans and Hispanic Americans are underrepresented in NINDS clinical research. NINDS supported clinical research would be greatly enhanced by testing of new methods, or use of previously proven methods, to ensure that the diversity in enrolled patients better represents the US population. Contact: Dr. Salina Waddy, 301-496-3102, Salina.Waddy@nih.gov
(10) Information Technology for Processing Health Care Data	10-NS-101 Neuroepidemiologic research from large existent databases. The evidence-base that supports the incidence and prevalence of many neurological disorders in the United States is often weak or lacking. Creative strategies to better define or answer neuroepidemiologic questions from large health care databases could enhance knowledge of the impact of neurological disorders in the US population. Contact: Dr. Deborah Hirtz, 301-496-5821, dh83f@nih.gov
(11)Regenerative Medicine	11-NS-101 Imaging neural plasticity. New methods to identify and track important processes related to human neural development and repair in the nervous system would open entire new fields of study in a variety of neurological disorders. Contact: Dr. Naomi Kleitman, 301-496-1447, nk85q@nih.gov
(12) Science, Technology, Engineering and Mathematics Education (STEM)	For this RFA, there is no NINDS-specific Challenge Topic in this Challenge Area.
(13) Smart Biomaterials - Theranostics	13-NS-101 Developing novel biomaterials to interfaces with neural activity. The burden of neurological illness could be advanced by development of smart biomaterials that enable interfacing with the nervous system to restore function and decrease disability. These might include biomaterials that allow more effective neural-computer interfaces, scaffolds to improve repair of injured nerve or spinal cord as well as neurotransmission across damage nerve or cord. Contact: Dr. Joe Pancrazio, 301-496-1447, jp439m@nih.gov 13-NS-102 Theranostics in neurological disorders. Personalized therapy for a large number of neurological disorders is impeded by inability to risk stratify patients. This is especially vexing in conditions in which there is an identifiable anatomic or functional abnormality that is known to be linked to a disabling condition but the risk in the overall population with the abnormality is low; i.e. unruptured intracranial aneurysm or arteriovenous malformation, asymptomatic internal carotid or vertebral artery atherosclerotic stenosis, impaired smell discrimination in Parkinson's disease, first seizure, febrile seizure, etc. Methods to identify those at highest risk, or extremely low risk of disabling event would enhance neurological outcomes, minimize risk of interventions, and improve cost-effectiveness. Contact: Dr. Wendy Galpern, 301-496-9135, wg71m@nih.gov
(14) Stem Cells	14-NS-101* Reverse engineering human neurological disease. It is now conceivable to reverse-engineer human neurological disease by generating and characterizing iPSCs from human control and patient populations. The relatively easy access of source tissue provides a means of elucidating patient-specific cell dysfunction or response to candidate therapeutics. Research topics can include maximizing derivation efficiency, maintenance, or reproducibility, studies of cellular differentiation, screening bioactive agents, or profiling the molecular signature as well as the functional properties of cells from controls vs. patients. There will be an emphasis on appropriate validation of iPS cells and their derivatives, evaluating the hetero/homogeneity of any cell populations to be screened and use of cellular assays relevant to normal development, organ function and disease. Contact: Dr. David Owens, 301-496-1447, do47h@nih.gov
(15) Translational Science	15-NS-101* Manipulating the blood-brain-barrier to deliver CNS therapies for Mental/Nervous System Disorders. Neuroscience discoveries have led to promising therapeutic strategies for treatment of severe neurological disorders. However, the blood brain barrier presents a major hurdle to delivering potentially exciting agents such as RNA therapies, genes, critical enzymes, antibodies, other molecular entities, or cell therapies. The challenge is to develop potentially useful means of CNS drug targeting and delivery systems. Contact: Dr. Tom Jacobs, 301-496-1431, tj12g@nih.gov 15-NS-102 Translation of Gene Silencing Therapeutics. Technologies for gene silencing (antisense RNA, morpholino RNA, RNAi, miRNA, site-directed excision/repair, etc) have been rapidly developed and refined in cell culture and rodent models of disease. RNAi strategies now utilize viral vectors to deliver and continually express the gene silencing construct. In some cases this can be accomplished in a regulated and/or allele-specific manner. To realize the potential of these technologies, however, experiments in non-human primates or appropriate large animal models, are necessary to determine the feasibility of this therapeutic approach for the treatment of chronic neurological/mental health diseases with either focal or diffuse pathologies. Contact: Dr. Margaret Sutherland, 301-496-5680, sutherlandm@mail.nih.gov 15-NS-103 Demonstration of "proof-of-concept" for a new therapeutic approach in a neurological disease. Entry into the NINDS translational research program requires evidence that a new therapeutic approach is efficacious in an animal or cell model of a neurological disease. The NINDS seeks grants to conduct research that establishes proof-of-concept sufficient to initiate a preclinical therapeutic development effort. Contact: Dr. Jill Heemskerk, 301-496-1779, jh440o@nih.gov 15-NS-104 Early-stage therapy development. Recent genetic/molecular discoveries in basic and disease research offer new opportunities for treatment of neurological disorders. This Challenge would support the transition of basic/disease research findings into the pipeline for pre-clinical development of therapeutics. This could include the identification and validation of new treatment targets and the development of cell-based assays or animal models for translational research. Contact: Dr. Laura Mamounas; 301-496-5745, lm92t@nih.gov 15-NS-105 Translational-2 research pilots. Translational-2 (T-2, or dissemination) research identifies and measures barriers to translating clinical trial findings into widespread practice, and develops and tests models and strategies to overcome those barriers, in order to reduce the burden of neurological disease. Despite the success of past neurological and neurosurgical trials and the potential impact of trial outcomes on public health, the actual utilization of many of these findings has been low. Studies of the barriers and strategies to overcome these barriers in clinical neuroscience are encouraged, as both will aid in the refinement of future clinical trials - such that barriers are taken into account when trials are designed - and in the development of clinical practice guidelines by nonfederal organizations. Both outcomes will enhance the impact of neurological/neurosurgical trials and will ensure that maximal health output is gleaned from these often costly public investments. Contact: Dr. Deborah Hirtz, 301-496-5821, dh83f@nih.gov 15-NS-106 Identifying mechanisms that underlie nervous system development and function. Despite a wealth of emerging data, determining the organizing principles that guide the development and function of the nervous system remains a challenge. Mechanistic studies that elucidate these principles at the molecular, cellular, and systems level are encouraged, as well as analyses of how normal mechanisms are perturbed in neurological and neurobehavioral disease. Contact: Dr. Robert Riddle, Phone: 301-496-5745 , Email: rr260c@nih.gov

NINDS Challenge Program Coordinator
Robert Finkelstein
Phone: 301-496-9248
E-mail: finkelsr@ninds.nih.gov

 

Financial/Grants Management Questions
Tijuanna Decoster
Phone: 301-496-9231
E-mail: decostert@ninds.nih.gov