Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (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

In 2012, the National Institute of Neurological Disorders and Stroke (NINDS) established a Parkinson’s Disease Biomarkers Program (PDBP) (https://pdbp.ninds.nih.gov/) for the purpose of rapidly identifying and developing potential biomarkers that would improve the efficiency and outcome of Phase II clinical trials and ultimately, advance the development of treatments for Parkinson's Disease (PD). Originally composed of a consortium of 10 scientific projects, the PDBP currently contains clinical, neuroimaging, and/or biospecimen data on over 1300 subjects, and is expanding to include data and specimens from BioFIND, the Udall Centers, the National Brain and Tissue Resource for PD & Related Disorders, and other NINDS Parkinson's disease-related projects. While the PDBP has been very successful in collecting and distributing standardized, high-quality, longitudinal clinical and biological data on patients with PD, recent workshops have identified opportunities for increasing the PDBP's utility by broadening the patient groups it includes.

On May 1-2, 2013, the NINDS collaborated with the National Institute on Aging (NIA) in organizing "Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities" (http://www.ninds.nih.gov/funding/areas/neurodegeneration/workshops/adrd2013/index.htm). This workshop was part of the 2012 National Plan to Address Alzheimer's Disease, and was complementary to NIA's Alzheimer's Disease Research Summit 2012. One of the Alzheimer's Disease-related dementias (ADRD) that was discussed at length during this workshop was Lewy Body Dementia (LBD, including Parkinson's Disease Dementia and Dementia with Lewy Bodies). Scientists who were expert in the LBDs developed prioritized research recommendations for advancing our understanding of this neurodegeneration. One of the top recommendations called for the creation of longitudinal clinical, biological, and imaging resources for the LBDs. Additional recommendations called for identifying genetic/epigenetic markers, developing diagnostic imaging approaches, and developing biomarkers for LBD. It was recognized that all of the latter recommendations could be facilitated by the establishment of the longitudinal resources endorsed by the former recommendation.

Shortly after this, on January 6-7, 2014, NINDS organized the Parkinson’s Disease 2014: Advancing Research, Improving Lives conference to inform ongoing and future efforts in PD research (http://www.ninds.nih.gov/research/parkinsonsweb/PD2014/index.htm). This conference provided an opportunity for neuroscience researchers, physicians, public and private stakeholders, and members of the public to discuss the significant challenges and identify the highest priorities for advancing basic, translational and clinical research on PD. Working groups from each of these three topic areas developed prioritized research recommendations designed to address emerging opportunities and critical needs for PD. Non-motor symptoms, particularly cognitive impairment in PD, were ranked among the top priorities, as a key target for clinical trials by the Clinical Research working group and as an important focus for defining disease signatures by the Translational Research working group.

Both of these workshops highlighted the scientific and stakeholder communities' keen interest in having an improved understanding of the pathophysiology, risks for, and early diagnosis of conditions in which parkinsonism and cognitive impairment co-occur. Since current research suggests that different pathophysiological mechanisms may underlie the numerous syndromes in which Parkinson's disease and dementia are co-morbid, this FOA invites applications to expand the NINDS PDBP's current collection of longitudinal clinical and biospecimen data to include data and samples from subjects who have been diagnosed with the LBDs, i.e., Parkinson's Disease with Dementia (PDD) or Dementia with Lewy Bodies (DLB).

Two types of projects will be considered responsive to this FOA:

1) Applications to collect clinical data, neuroimaging data, whole blood, plasma, serum, CSF, urine peripheral blood mononuclear cells (PBMCs) for induced pluripotent stem cell (iPSC) derivation and/or other key specimens from patients with PDD or DLB. Applicants may propose to collect samples from one of these patient populations, or from both populations. Whole blood, plasma, serum, PBMCs and cerebrospinal fluid (CSF) will be collected at minimum.

2) Hypothesis-driven clinical research to discover potential biomarkers for the LBDs. Proposed biomarkers may be based on a single measure or a panel of measurements, and may seek to improve differential diagnosis, identify risk of disease, or predict disease progression. It is preferable for applicants to have access to subjects with either PDD or DLB (or to both populations) and be collecting clinical data and biological specimens from them. However, high-quality data and samples available from other sources may be used as a sole resource or in addition to new data collection. All applicants are encouraged to use existing data and specimens in the PDBP for control data, though additional controls may be proposed if appropriate and unavailable in the PDBP. In cases where other studies or repositories are being used, permission should be obtained from the source prior to application submission See also the instructions in Section IV.2.

Ideally, studies should be longitudinal. Whereas whole blood for DNA and PBMCs need only be submitted once (at the time of initial visit), longitudinal samples (other than CSF) and associated clinical data should be collected every six months. CSF should be collected at least once per year for the duration of the grant. Biospecimen and clinical data collection for a given time point must co-occur at the same subject visit and be submitted to the NINDS Biomarker Repository and the PDBP Data Management Resource (DMR) within 24 hours of each visit. Cross-sectional studies in unique populations may be acceptable, but applicants are encouraged to contact program staff to discuss this option. For all studies, a timeline for data and biospecimen collection must be included and justified in the application.

Ancillary studies to existing cohorts for the collection of new data and biospecimens may be appropriate. However, subjects enrolled in biomarker studies as a component of existing, ongoing clinical trials are not appropriate for this FOA because of the risk of un-blinding and the unknown impact of the tested therapeutics on pathophysiology. All applicants are encouraged to focus on the recruitment and inclusion of women and minorities, as well as individuals from other populations that are traditionally underrepresented in clinical research. Although not required, applications with special outreach programs to such populations will be considered to be a high priority for this FOA. For further details, see: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-089.html.

Note that costs for biospecimen collection are not included as a component of the NINDS Biomarker Repository, and some costs for the biospecimen banking will be borne by the grantees utilizing this resource. In the case of PBMCs, the NINDS Cell Repository will generate the cell lines and cover the costs of the kit components required for collection. When planning the application budget, applicants are strongly advised to consult with the NINDS Biomarker Repository staff (https://www.biosend.org/).

All applications will be required to collect standard PDBP clinical instruments (see: https://pdbp.ninds.nih.gov/jsp/data-management-resource.jsp) in addition to the Neuropsychiatric Inventory. If additional clinical assessments are proposed, the NINDS strongly encourages researchers to use those endorsed by the NINDS Common Data Elements for PD (see: http://www.commondataelements.ninds.nih.gov/PD.aspx#tab=Data_Standards). Biological specimens should conform to the specimen collection protocols of the NINDS Biospecimen Repository (see: https://www.biosend.org/). Consent forms 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 Biomarker Repository and NINDS PDBP DMR requirements and achieving the goals of the program.

If an application plans to utilize the infrastructure or resources of existing projects, it 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. Assurance that all samples and data will be collected under proper consent to allow broad sharing should be documented. Prior to award, the applicant must provide to NINDS 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, as appropriate and consistent with achieving the goals of the program.

Animal or other disease model studies are not appropriate for this FOA. Clinical trials are not appropriate for this FOA. Replication studies or validation studies of commonly-used approaches are strongly discouraged. Projects that propose the collection of biological specimens and data that will not be submitted to the NINDS Biomarker Repository/DMR respectively will not be review.

Applications proposing efforts that are duplicative of DMR functions or responsibilities will not be funded. 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 Biomarker 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. For those with existing studies already utilizing a data management core or resource, data must be federated with the DMR as appropriate and consistent with achieving the goals of the program. 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 Biomarker 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. 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 Biomarker Repository standards. Note that these awards will be managed as cooperative agreements; therefore, projects that do not comply with terms, conditions, and established milestones of the award and of this program may be terminated early.

Due to the unique requirements of the NINDS PDBP, applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on when planning an application (see Agency contacts, Section VIII). This early contact will provide an opportunity to clarify the applicant's understanding of the goals of this FOA and NINDS policies and guidelines, including those pertaining to the PDBP DMR and NINDS Biomarker Repository. 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.

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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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)

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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must obtain 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, including Supplemental Grant Application Instructions 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 activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Debra Babcock, Ph.D., M.D
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. The application must identify key personnel in the application whose responsibility will be to ensure and facilitate data quality, transfer, sharing, and biological specimen submission to the DMR and NINDS Biomarker Repository.

All instructions in the SF424 (R&R) Application Guide must be followed. As noted above, costs for biospecimen collection are not included as a component of the NINDS Biomarker Repository; some costs for biospecimen banking should be included in the applicant's budget.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Research Strategy: Applications should provide details on how the application will comply with PDBP DMR and NINDS Biospecimen Repository policies and procedures. If additional measurements are proposed, the applicant should indicate whether these comply with NINDS common data elements. .

Milestones are goals that create go/no-go decision points in the project; all applicants must include milestones that specify clear and quantitative criteria for success. At minimum, milestones should include timelines for 1) subject recruitment, 2) complete, clean and accurate data submission, and 3) quality accepted collection and submission of biospecimen samples. All proposed milestones should conform to the policies and procedures of the PDBP DMR and NINDS Biomarker Repository.

Letters of Support: If an application plans to utilize the infrastructure or resources of existing projects letters of support from the project leadership detailing approval, feasibility, terms of collaboration and data sharing must be included. In cases where other studies or repositories are being used, permission should be obtained from the source prior to application submission and documented in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date 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 SF424 (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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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.

Reviewers will provide an overall impact 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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 this NINDS resource and will it be useful to future researchers for biomarker discovery? Is the project within the scope and does it further the goals of biomarker discovery?

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?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? Are milestones addressing timely subject recruitment, complete, clean and accurate data submission, and quality collection and submission of biospecimen samples included with the application? Do they create go/no-go decision points in the project and include clear and quantitative criteria for success? Is the approach compliant with PDBP policies and procedures?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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 score, but will not give separate scores for these items.

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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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 score.

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.

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).

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) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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. Assignment to a Scientific Review Group 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 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 be assigned to the appropriate NIH Institute or Center. 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. Such priorities include compliance with the policies and procedures of the PDBP and NINDS Biospecimen Repository.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this 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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 as appropriate;
• 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 as appropriate;
• 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 at in-person PDBP meetings 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 research on Parkinson's disease and parkinsonisms, 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 as appropriate).

Areas of Joint Responsibility include:
None

Other PDBP Components

Steering Committee

The NINDS has established an independent steering committee (SC) to assist in determining the broad direction of the PDBP. The SC provides input regarding new research findings and the relevance of that in the context of funded and proposed projects.

Biological Resource Acquisition Committee

The PDBP Biological Resource Acquisition Committee (BRAC) evaluates 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 PDBP Data Acquisition Committee (DAC) assures that data use requests are compliant with data use policy and procedure requirements prior to data distribution, and monitors any security breaches or other concerns.

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 appropriately: (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 based on existing studies in which databases already exist or have been created via other resources may maintain those databases 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 Research Performance Progress Report (RPPR) 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.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Debra Babcock, M.D., Ph.D.
National Institute of Neurological Disorders & Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]

Tijuanna E. DeCoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

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 Part 75.