Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	Studies in Parkinson's Disease Biomarkers Discovery (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	April 19, 2012 - See Notice NOT-NS-12-015. Frequently Asked Questions (FAQs) for this RFA have been created.
Funding Opportunity Announcement (FOA) Number	RFA-NS-12-011
Companion Funding Opportunity	RFA-NS-12-010, U18 Research Demonstration Cooperative Agreements
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.853
Funding Opportunity Purpose	The purpose of this funding opportunity announcement (FOA) is to 1) support hypothesis driven clinical research to discover biomarkers that will improve the efficiency and outcome of Phase II clinical trials for Parkinson’s Disease (PD) and 2) support the collection of clinical data and new biological specimens that will be used for biomarker exploratory efforts under the NINDS Parkinson’s Disease Biomarkers Program (PDBP). Applications may include both of these goals if justified. Studies using either existing or new cohorts may be appropriate. For all applications, applicants must describe statistical justification for the number of subjects/samples proposed and a clear scientific rationale for the range and types of subjects/samples to be collected. Broad sharing of data and biological specimens with academic, industry and government researchers is a critical feature of the PDBP generally and of this FOA specifically, in order to provide valuable research resources for the scientific community to advance Parkinson’s Disease research in an efficient and effective manner (consistent with applicable laws, regulations, and policies); therefore, all subjects in any proposed study must be properly consented to allow appropriate sample and data distribution to researchers in academics and industry. The NINDS Repository and the PDBP data management resource (DMR) contracts will be utilized for the banking and distribution of new biospecimens and biological and clinical data, respectively. This FOA is only for studies related to human biomarkers; animal or other disease model studies are not responsive to this FOA. A timeline including milestones is required for all studies. Annual milestones will provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years.

Posted Date	March 16, 2012
Open Date (Earliest Submission Date)	April 23, 2012
Letter of Intent Due Date	April 23, 2012
Application Due Date(s)	May 23, 2012 , by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable.
Scientific Merit Review	July, 2012
Advisory Council Review	August, 2012
Earliest Start Date(s)	September 30, 2012
Expiration Date	May 24, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Background

Recently, there has been considerable progress in our understanding of the biology of Parkinson’s disease (PD). However, several factors currently impede therapy development and clinical study design for neuroprotective agents. These include the limited ability to detect early stage PD prior to the onset of motor signs, inadequate measures of processes or pathways related to disease pathogenesis, and the lack of biomarkers that define disease progression. To overcome these obstacles, the National Institute of Neurological Disorders and Stroke (NINDS) is establishing a Parkinson’s Disease Biomarkers Program (PDBP).

The overall purpose of the NINDS PDBP is to rapidly identify and develop potential biomarkers to improve the efficiency and outcome of Phase II clinical trials and advance therapeutic development for PD. The NINDS PDBP will coordinate the efforts of multiple stakeholders interested in the identification and development of diagnostic, progression or prognostic PD biomarkers and related assays by: 1) standardizing data and biospecimen collection and management across new PD cohort studies; 2) enhancing efforts of current PD biomarker studies through ancillary projects that support additional well characterized biospecimen collection; 3) accelerating the discovery of new biomarkers; and 4) fostering and expanding collaborative opportunities for all stakeholders.

Initially the NINDS PDBP will include four key components:

1) Biomarker hypothesis testing and collection of clinical data and biospecimens;

2) Technology-based studies. These could attempt to identify novel PD biomarkers through the use of genomic, metabolomic, proteomic, histologic, cellular, or neuro-imaging based platforms or they could attempt to develop of assays for reliable measurement of single or multiple molecular analytes that are related to diagnosis, progression or prognosis of PD;

3) Biospecimen banking and distribution (including but not limited to serum, plasma, CSF, whole blood, and fibroblasts) through the NINDS Repository contract (http://ccr.coriell.org/Sections/Collections/NINDS/?SsId=10); and

4) Data management through a contract-supported Data Management Resource (DMR) that will utilize common PDBP clinical data elements for the standardization and sharing of biomarker-related data (see below).

In collaboration with the PD research community, NINDS will integrate all of its current and future PD biomarker projects within this program. We expect this approach to remain flexible in order to adapt to advances in the field as they occur. Public sharing of data and biospecimens collected is required under the PDBP.

Scope of Research

This FOA will support two types of projects: 1) hypothesis driven research to discover clinical biomarkers to improve the efficiency and outcome of Phase II clinical trials or 2) the collection of clinical data and biological specimens, which will be used for biomarker exploratory efforts under the NINDS Parkinson’s Disease Biomarkers Program (PDBP). Applications may include either or both of these goals if justified. Studies assembling new cohorts, or ancillary studies to existing cohorts for the collection of new biospecimens and data, may be appropriate. However, subjects enrolled in biomarker studies as a component of existing, ongoing clinical trials populations are not appropriate for this FOA because of the risk of un-blinding and the unknown impact of tested therapeutics on underlying pathogenesis. Such studies may be appropriate in response to PAR-09-263 (Ancillary Studies in Clinical Trials of CNS/PNS Disorders). For all studies, a timeline must be included and justified in the application. All applications must delineate how the planned project will fill a gap in the PD biomarkers field through collection of valuable biospecimens and clinical data, and where justified, the additional testing of specific hypotheses directed at PD biomarker discovery. Animal or other disease model studies are not responsive to this FOA. Every application should provide justification for project alignment with the PDBP goals as described above.

Examples of types of applications that will be responsive to this FOA include:

I. Hypothesis-driven Clinical Research to Discover Parkinson’s Disease Biomarkers

Applicants may propose to evaluate potential biomarkers for Parkinson’s disease via a range of strategies including those in the following categories:

• Identification of clinical measures that can predict progression better than current clinical scales (such as olfaction, gait variation, autonomic function, other non-motor or systemic findings).
• Laboratory based projects that use biospecimens collected via the collection parameters outlined below.
• Imaging projects that could include studies of brain structure, function, network measures or molecular imaging. Studies should involve imaging parameters that could be rapidly translated into clinical trials and practice. If specialized technical approaches are proposed, including the use of new ligands, the applicability to the translation of biomarkers into trials and practice must be made clear.

PDBP hypothesis-driven projects under this FOA can be stand-alone, or can be combined with a clinical data and biological specimens project (including non-hypothesis-driven) as outlined below.

II. Collection of Clinical Data and Biological Specimens

Researchers may propose evaluation of subjects and the collection of clinical data and valuable biological specimens (not necessarily hypothesis-driven). Ideally, proposed clinical studies should be longitudinal. Whereas whole blood for DNA need only be submitted once (at the time of initial visit), longitudinal samples and associated clinical data (other than CSF and fibroblasts) should be collected every six months. CSF should be collected at least once a year for three years minimum. Biospecimen and clinical data collection for a given timepoint must occur at the same subject visit and be submitted to the NINDS Biorepository and DMR within 24 hours of each visit. Cross-sectional studies in unique populations may be acceptable. NINDS will make these biosamples and associated de-identified clinical data available to investigators proposing meritorious hypothesis-driven biomarker discovery research.

Two types of possible cohorts are envisioned as being useful for this type of study:

1) New Cohorts: Investigators may propose new cohorts if they address a particular clinical, genetic or demographic niche that will be valuable for subject stratification for biomarkers discovery. Cohorts may be cross-sectional or longitudinal, and could include but are not limited to:

• Cohorts based on genetics: e.g., those carrying specific genetic risk factors (e.g. GBA, LRRK2) or extended, apparently Mendelian pedigrees;
• Cohorts based on age of onset: e.g., early onset vs. typical age of onset PD
• Cohorts based on stage of disease: especially patients with early stage, newly diagnosed or high (ideally Hoehn and Yahr stages 1-3);
• Cohorts based on response to medication: e.g. medication-induced dyskinesias or other pharmacologically specific categories;
• Neuropsychiatric subsets: e.g., Parkinson’s Disease Dementia, hallucinosis.

2) Existing Cohorts: Investigators may propose ancillary studies to existing cohorts for the purpose of adding clinical data and biospecimen collections to the PDBP. Such studies might involve the entire cohort that is participating in an ongoing clinical study (not a clinical trial), or selected subsets of the participants. If an application plans to utilize the infrastructure or resources of existing projects, letters of support detailing the feasibility, terms of collaboration and data sharing must be included. Ancillary studies must not interfere with the parent study and must not place undue burden on participants. Approved procedures and policies from the parent study must be followed and must have patient consents that allow broad sharing of de-identified clinical data and deposition of biospecimens in the NINDS Repository.

While this FOA is specifically intended for PD biomarkers projects, data collection from subjects with other synucleinopathies (e.g. Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB)) may be proposed for comparison or as a component of a study that will inform future clinical trials, as long as this is clearly justified.

Application Requirements

Clinical Data Requirements

In order to maximize data standardization across studies, the NINDS strongly encourages researchers to use the NINDS Common Data Elements which are available at http://www.commondataelements.ninds.nih.gov/General.aspx. The PDBP DMR will develop web-based forms to assure ease of data entry and quality assurance. Some of these assessments may be self-administered in order to reduce subject and study burden. PDBP clinical projects will be required to include the following General and PD-specific CDEs:

General CDEs

All core General CDE items and forms will be required in the following domains for all subjects:

• Participant/Subject Characteristics (Demographics)
• Participant/Subject History (Medical History and Behavioral History)
• Assessments and Examinations (Physical/Neurological Exam, Vital Signs, Laboratory Tests and --Biospecimens/Biomarkers)
• Treatment/Intervention Data (Prior and Concomitant Medications)
• Protocol Experience (Inclusion and Exclusion Criteria, Informed Consent and Enrollment)

PD-Specific CDEs

All core and the following recommended items and forms will be required in the domains listed below, both for PD subjects and for those at risk for PD (i.e., pre-symptomatic, gene carriers, etc.). Items that are duplicative of those in the General CDEs need not be collected twice.

• Participant/Subject Characteristics (Demographics)
• Participant/Subject History and Family History (Medical History, Family History)
• Assessments and Examinations (MDS-UPDRS, Hamilton Depression and Anxiety Rating Scales, Montreal Cognitive Assessment, Epworth Sleepiness Scale, RBD Screening Questionnaire, and University of Pennsylvania Smell Identification Test)
• Treatment/Intervention Data (PD Medication Log)
• Outcomes and End Points (PDQ-39).
• Additionally, the Schwab and England ADL Scale will be required.

In addition to the above, PDBP applicants may employ supplementary assessment and measurement tools if relevant to addressing the specific hypotheses proposed in their application. If other tools are proposed, applicants are strongly encouraged to use those suggested or provided by the NINDS CDE program.

Biospecimens

Biospecimens collected could include whole blood, plasma, serum, cerebrospinal fluid (CSF); ideally, a resource development application under this FOA should plan to collect all of these. Fibroblasts may be appropriate for special populations, such as those with known genetic variants causal for disease; collection of these or other biospecimens must be justified in the application and will require programmatic approval.

Consent forms (submitted as appendix material) must make it clear that any biological samples and de-identified clinical data will be shared with academics or industry and must be consistent with the NINDS Repository and NINDS PDBP data management resource consent requirements (see https://ccr.coriell.org/Sections/Collections/NINDS/InvestigatorFAQ.aspx?PgId=150&coll=ND). A copy of the consent form for each subject should be kept on file by the investigator but does not need to be sent with each sample.

Biospecimens must be collected under protocols of the Parkinson Progression Markers Initiative (PPMI, see http://www.ppmi-info.org/study-design/research-documents-and-sops/). If site logistics are challenging regarding the PPMI protocols, then the Alzheimer’s Disease Neuroimaging Initiative protocols could be used as an alternative, as long as they are justified (see ADNI, see http://www.adni-info.org/Scientists/Pdfs/adni_protocol_9_19_08.pdf).

Newly collected samples must be submitted to the NINDS repository within 24 hours of each subject visit. Existing sample collections may be submitted to the repository if specific conditions for NINDS approval are met. In general, the following volumes must be submitted to the NINDS Repository for each sample type for each visit submission in order to be considered acceptable and counted towards the deliverables for each project:

• Plasma/Serum: minimum 6 milliliters
• Whole blood: (for DNA extraction) minimum 6 milliters (initial visit only)
• Whole blood for other studies minimum 6 millileters (in addition to that for DNA at initial and also other than initial visits)
• Pax-gene tube (for RNA) minimum 8 milliliters
• CSF: minimum 10 milliliters (local analyses to include cell count, total protein, glucose, submitted to DMR)

All fibroblasts must be sent as skin biopsies directly to the NINDS Repository; please contact NINDS Program staff if you plan to submit this type of material. Fibroblast lines (already established) will not be accepted except under special circumstances, requiring PDBP Program staff approval. All biospecimens submitted must be accompanied by a full set of clinical data elements as defined above.

Projects that propose the collection of biological specimens and data that are not submitted to the NINDS Repository/DMR respectively will not be considered for funding.

Imaging Requirements

Applicants may propose the collection of imaging data if these data will lead directly to the development of a potential biomarker for PD. Funds may be requested to collect PET, SPECT, and/or MRI (e.g., DTI, MRS, fMRI, etc.) scan information if the applicant can clearly describe the relevance of the approach to the PDBP effort. Priority will be given to applicants who are proposing the use of novel but existing ligands, sequences, or multi-modal combinations; ligand development, replication studies or validation studies of commonly-used approaches are strongly discouraged in this biomarker discovery FOA (although it is anticipated that validation/replication studies will be supported by other mechanisms). If appropriate, investigators should use the NINDS PD Imaging Diagnostics templates for data collection whenever possible (see: http://www.commondataelements.ninds.nih.gov/PD.aspx#tab=Data_Standards). Where possible the use of standard imaging formats like the Neuroimaging Informatics Technology Initiative data format, NIfT-I, http://nifti.nimh.nih.gov/nifti-1/ should be used to enable comparison with imaging data from other data resources.

Ancillary Study Requirements

For studies that are ancillary to an already existing project, the applicant Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must provide documentation from the parent study leadership of approval to use existing study infrastructure, patient cohorts, patient samples, and any other data sought from the parent study. As with other studies funded under this program, assurance that all samples and data will be collected under proper consent to allow broad sharing should be documented. Informed consent forms for the parent clinical study and the ancillary studies, if different and/or if available, should both be included as part of the appendix. It is recommended that applications submitted under this program have clear language in the informed consent form(s) that distinguishes ancillary studies from the clinical studies with which they are linked. It is also recommended that the following items be clarified in the consent documents: (1) the additional samples/specimens/examinations that will be collected as part of the ancillary study; (2) the right of the subjects to refuse to participate in the ancillary study and still participate in the clinical study; and (3) absence of cost to the subject for participation in the ancillary studies. Any incentives provided to subjects to participate in the ancillary studies (if in addition to those under the parent study) should be clearly described and strongly justified.

Prior to award, the applicant must provide to the NIH funding Institute a memorandum of understanding signed by the applicant, an appropriate representative of the applicant institution, the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of the parent clinical study and his or her academic institution, an appropriate representative of the sponsor of the parent clinical study, if applicable and not one of the above. This memorandum will confirm agreement among the various parties and will outline the terms and conditions of the agreement in the following areas all of which must be compliant with PDBP policy requirements: 1) ownership, analysis, access and release of data from the ancillary studies; 2) method and timing of access to the data from the parent clinical study that are needed to analyze the ancillary studies; 3) documentation of quality assurance procedures for both the parent clinical study and the ancillary studies; 4) documentation of Data and Safety Monitoring procedures for the parent clinical study and ancillary study if appropriate; 5) ownership of intellectual property developed by the ancillary studies; and 6) plan for publication of the ancillary study results.

No clinical trials will be supported under this FOA.

Statistical Requirements

All applications must include statistical justification for the number and types of subjects recruited. Key personnel with statistical expertise should be identified for each project in order to assure alignment of the individual study recruitment goals with the overall goals of the DMR and the PDBP.

Data Management Resource (DMR)

The PDBP Data Management Resource will provide an essential data coordination tool for the entire PD biomarker research community through the development of a web-based data management system that provides tools to PDBP supported projects for both the collection and quality assurance of data in a standardized format. The DMR will also coordinate the assembly of de-identified data into a common database thus enabling the query and distribution of aggregate data for the acceleration of PD biomarker discovery and validation. The PDBP data management resource will synchronize efforts across government and non-government organizations involved in PD biomarker research through the creation of a federated database. Federation will enable the owner of the non-DMR dataset to maintain the data sharing/data access policies of that dataset. A summary and access request to the federated datasets will be hosted on the NINDS DMR web portal. Data users with access to other databases will be able to receive a report in response to a data query that includes aggregated data from all approved sources.

Applications proposing efforts that are duplicative of DMR functions or responsibilities will not be funded in part or at all. Activities that are the sole purview of the DMR include: 1) development of standardized electronic data forms, data formats and software for use across multiple cohorts and projects; 2) development of software to support subject scheduling, site tracking, and facilitation and coordination of de-identified clinical and biospecimen data collection across multiple new and existing cohorts and projects through an easy to use web-based entry system for submitters; 3) quality assurance checks of data entry and collection; 4) development of a user-friendly query system for users to evaluate availability of data and biospecimens within and across PD biomarker projects; 5) development of aggregate data report formats that are user-friendly and supported by well documented data dictionaries; 6) training for both data submitters and data users; 7) coordination of data and biospecimen summary reports and postings in collaboration with the NINDS Repository; and 8) public outreach for data submission and data use. Development of all electronic data entry forms and quality assurance checks of de-identified data will be done by the DMR. The study site must identify at the time of application, key personnel whose responsibility will be to ensure and facilitate data quality, transfer, sharing, and biological specimen submission to the DMR and NINDS repository respectively. For those with existing studies already utilizing a data management core or resource, data will not be required to be entered twice or transferred, but, must be federated with the DMR. Deposition of all data into the PDBP DMR should occur in real time.

Milestones and Timeline

Milestones for all projects will specify compliance with NINDS Repository and DMR terms. Annual milestones must be provided in the context of a study timeline. These milestones will provide clear indicators of a project's continued success or emergent difficulties. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should include timely subject recruitment, complete, clean and accurate data submission and quality accepted collection and submission of biospecimen samples. The milestones will weigh heavily in the peer review process and poorly-constructed milestones will negatively impact scores. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment. Both data and biospecimen collection must meet DMR and NINDS repository standards. Note that these awards will be managed as cooperative agreements; therefore, projects that do not comply with sharing requirements of this program may be terminated early.

Due to the unique requirements of the NINDS PDBP, applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application (see Agency contacts, Section VIII). This early contact will provide an opportunity to clarify the applicant's understanding of NINDS policies and guidelines, including the scope of projects within the PDBP. These discussions also provide important information and guidance on how to develop an appropriate timeline and milestone plan, which are subject to peer review under this program.

Funding Instrument	Cooperative Agreement
Application Types Allowed	New The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NINDS intends to commit $4M in FY 2012, to fund an estimate of 6 awards.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is five years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Katrina Gwinn MD
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd Room 2143
Bethesda MD 20892
(For Fed Ex Deliveries, use
Rockville, MD 20852)
Telephone: 301-496-5745
Fax: 301-502-1501
Email: gwinnk@ninds.nih.gov

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

For this application, the following must be included:

Milestone plan: A milestone plan, under separate headings, must be included in the Research Strategy section of the application (not Appendix). For new cohort studies, the milestone plan must include a timeline for recruitment, number of visits per year and over the course of the study, and biospecimen collection. In the case of ancillary studies that will require additional clinical assessments and/or require additional biospecimen collection, the milestone plan should also outline the number of subjects from the parent cohort required for the ancillary study, the clinical sites involved and the timeline for data/biospecimen collection.

Data Sharing Plan: A data sharing plan is expected to be included in the body of the application (not Appendix). Clinical Data should be submitted in real time to the DMR via provided web-based forms; if real time submission is not possible, then all data should be submitted within one day of collection to the DMR. For ancillary studies using existing cohorts and infrastructure, broad sharing of de-identified clinical, laboratory data and biospecimens should not be restricted by parent study policy or procedures.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The resource Sharing Plan should follow the resource sharing policy of the PDBP program, which includes deposition of biospecimens with the NINDS Repository and data deposition with the DMR. .

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modifications:

The Appendix should contain the following materials:

• Study protocol
• Consent forms, if available

If an ancillary study to an existing project, include also:

• the protocol for the parent study
• investigator's brochure, if applicable, for the parent clinical study
• consent forms (if ancillary, for both the parent clinical study and the ancillary studies, if different)
• Written agreement to conduct the ancillary study from parent clinical study sponsors.

IRB approval of the informed consent form(s) is not required at the time of submission of the application. However, drafts of informed consent form(s) must be included.

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following: Studies responsive to this FOA support the development of clinical and biological resources for future biomarker discovery that will have a significant impact on the analysis of disease progression in PD patients. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding of PD biomarkers.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is the collection proposed important to the development of an NINDS resource which will be useful to future researchers for biomarker discovery? Is the project within the scope and does it further the goals of PD biomarker discovery?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? If imaging studies are proposed (PET, SPECT, and/or MRI) is the applicant proposing the use of novel but existing ligands, sequences, or multi-modal combinations and not simply replication studies or validation studies of commonly-used approaches?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Does the application avoid undue subject burden? Is a timeline included which delineates clear and feasible milestones? If ancillary studies to an existing project are proposed, are they feasible within the framework of the parent study, and are supporting documents provided?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDS) Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with data and resource sharing policies.

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining experimental approaches, designing protocols, setting project milestones and conducting experiments;
• Adhere to existing PDBP study policies regarding data and biospecimen sharing and other policies that might be established during the course of this activity;
• Report to NINDS Program staff regarding timeline and milestone achievement during the course of the project, as delineated in the terms and conditions of award;
• Submit annual progress reports during the funding period, in a format as agreed upon by NINDS program staff;
• Accept and implement any other common guidelines and procedures developed for the PDBP initiative and approved by NINDS program staff;
• coordinate with other projects under the PDBP, including sharing of data with a centralized data management resource and other PDBP sites;
• Attend in-person PDBP meetings up to twice per year organized by NINDS and present up to date findings (including unpublished results) on ongoing projects.

Awardees are expected to make new information and materials known to the research community not only in the bi-annual PDB P meeting but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.

Publications

The PD(s)/PI(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgement of NINDS and PDBP support. Timely publication of major findings is required.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientists will be to facilitate and not to direct the activities.

The NINDS Project Scientist will:

• Contribute to the adjustment of research protocols, project milestones or approaches as warranted;
• Serve as a liaison between the awardees, the NINDS Advisory Council and the larger scientific community;
• Coordinate the efforts of the awardee with others engaged in PD research, including other awardees under this FOA and those involved in related NINDS programs;
• Serve on subcommittees of the PDBP External Liaison Group as appropriate;
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements.

Areas of Joint Responsibility include:

None

Other PDBP Components

Scientific Liaison Group

The NIH will establish an independent scientific liaison group (SLG) to assist in determining the broad direction of the PDBP. The SLG will provide input regarding new research findings and the relevance of that in the context of funded and proposed projects.

Resource Acquisition Committee

The Resource Acquisition Committee will evaluate requests for biospecimens based on transparent criteria for distribution towards PD biomarkers discovery projects. It is intended that biospecimens be available for research studies by academics and industry investigators.

Data Acquisition Committee

The Data Acquisition committee will assure that data use requests are compliant with data use policy and procedure requirements prior to data distribution and monitor any security breaches or other concerns.

Due to the unique requirements of the NINDS PDBP, applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning stage of their application (see Agency contacts, Section VIII). This early contact will provide an opportunity to clarify the applicant's understanding of NINDS policies and guidelines, including the scope of projects within the PDBP. These discussions also provide important information and guidance on how to develop an appropriate timeline and milestone plan, which are subject to peer review under this program.

Opportunities for Partnership

Projects involving partnerships with industry, small businesses or non-government organizations are encouraged under this FOA. The policy of the NIH is to make available to the public the results and accomplishments of the activities that it funds. To ensure that research resources are made accessible to the broader biomedical community, NIH expects applicants who respond to this funding opportunity to submit a plan for: (1) sharing the research resources generated through any grants awarded and (2) addressing how they will exercise intellectual property rights, should any be generated through an award, while making such research resources available to the broader scientific community consistent with this initiative. Projects existing studies in which databases already exist or have been created via other resources may be maintained under those projects, but not funded via this program. However, it is expected that these databases will become federated under the DMR.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Katrina Gwinn MD
National Institute of Neurological Disorders and Stroke
Telephone: 301-496-5745
Email: gwinnk@ninds.nih.gov

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: (301) 496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: (301) 496-9231
Email: decostert@ninds.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.