Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
This RFA is developed as an NIH roadmap initiative (http://nihroadmap.nih.gov). All NIH Institutes and Centers participate in roadmap initiatives. The RFA will be administered by the

National Eye Institute (NEI), (http://www.nei.nih.gov) on behalf of the NIH.

Title: Nanomedicine Development Centers (PN2)

Announcement Type
This is a re-issuance of RFA-RM-04-018, which was previously released on May 4, 2004, and NOT-RM-05-010, previously released on April 13, 2005.

Update: The following update relating to this announcement has been issued:

• March 1, 2006 (NOT-RM-06-014) - Addendum to announce that prior to submitting a full application for a PN2 award, potential applicants are required to submit a five-page Concept Approval Letter by March 15, 2006.

NOTICE: This RFA is an open competition. In fiscal year 2005, a network of four Nanomedicine Development Centers was awarded. The NIH is expanding this network in fiscal year 2006 with additional centers through this RFA.

Due to the specialized nature of this RFA, approval to submit an application will be granted based upon a letter from applicants (maximum five pages) that addresses the vision and goals of a Nanomedicine Development Center in the context of the network of currently funded centers. This permits NIH staff to determine whether there is sufficient scientific and programmatic interest. The receipt date of this concept approval letter is March 15, 2006

A public information meeting will be held in Bethesda, MD on January 27, 2006 to discuss this RFA and the NIH Roadmap Nanomedicine Initiative (see NOT-RM-06-010). The meeting will be broadcast on the internet at http://videocast.nih.gov.

Request For Applications (RFA) Number: RFA-RM-06-007

Catalog of Federal Domestic Assistance Number(s)
93.867

Key Dates
Release Date: January 26, 2006
Concept Approval Letter Receipt Date: March 15, 2006
Approval Notification Date: April 17, 2006
Letters of Intent Receipt Date(s): N/A
Application Receipt Dates(s): June 23, 2006
Peer Review Date(s): July-August, 2006
Council Review Date(s): September, 2006
Earliest Anticipated Start Date: September 25, 2006
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: June 24, 2006

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

• Important - Prior approval is required before submitting applications in response to this RFA. Concept approval letters must be submitted by March 15, 2006. The primary purpose of the letter is to give NIH staff and reviewers an overview of the proposed vision, goals, and approach, without requiring investigators to prepare costly, time-consuming applications.
• The NIH invites applications for funding Nanomedicine Development Centers (NDC) by the NIH Nanomedicine Roadmap program. These centers will join a network of four NDCs that were awarded in fiscal year 2005.
• Each multidisciplinary center will consist of a team of clinicians, biologists, engineers, physical scientists, and mathematicians that work together to investigate the physical properties of molecules and molecular complexes in living cells in order to understand design principles of the native molecular machinery that operates inside cells. The long-term (10-year) goal is to engineer molecular components and complexes in cells to treat disease and/or repair tissue.
• It is anticipated that two, three or four new, five-year awards will be made under this RFA.
• The NIH intends to commit up to $1.4 million per year per center in the first year, Thereafter, it is expected that a base amount of $1.2 million per year will be available for each center during the award period. Additional program funds of up to $12 million are expected to be allocated among centers on a competitive basis in the third through the fifth year of the award period.
• The NIH Research Development Centers (PN2) award mechanism will be used.
• Awards will be issued as an other transaction under Flexible Research Authority that permits modified peer review and award management.
• Eligible organizations include domestic for-profit or non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State and local governments; eligible agencies of the Federal government. Foreign institutions/organizations are ineligible to apply but may collaborate with US institutions and may receive funding.
• Eligible Principal Investigators include any individual with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

The NIH Roadmap is a series of initiatives designed to pursue major opportunities in biomedical research and to fill gaps in current knowledge that cannot be addressed by any single NIH institute or center. The goal is to enable the rapid transformation of new scientific knowledge into tangible benefits for public health (http://nihroadmap.nih.gov/).

Nanomedicine is one of nine major initiatives included in the NIH Roadmap. Because Nanomedicine is an emerging biomedical discipline, the NIH engaged the biomedical research community to help define and develop concepts and a framework to stimulate work in this field. A two-year planning process, (see http://grants1.nih.gov/grants/guide/rfa-files/RFA-RM-04-018.html) culminated in the establishment of a collaborative national network of Nanomedicine Development Centers (NDC). The first four centers were awarded in fiscal year 2005. The current RFA solicits applications for additional centers that will expand the network by addressing complementary models, topics, medical targets, and approaches to the work of funded centers.

The long-term goal of the Nanomedicine Roadmap initiative is to exploit detailed information on the design of molecules and supramolecular assemblies in living cells to improve human health. Envisioned as a ten-year initiative, in the first five years, the NDCs will focus on quantitative characterization of the machinery inside living cells that underlies cell function and regulation. Decisions on the biological systems to study and the nature of measurements to be made, will be guided by the principle that the precise control required to manipulate cellular components will depend upon understanding and using engineering principles. The NDCs will merge the use of existing and novel experimental and modeling approaches to develop and test methods for intervening in cellular processes. Those methods will be used to precisely manipulate cellular processes by repairing intracellular structures at the nanoscale or building new structures for biomedical use, to prevent and treat disease and repair tissue. These are bold goals and achieving them will entail acceptance of higher levels of risk by applicants and the NIH.

Background

Nanomedicine refers to highly specific medical intervention at the molecular scale for curing disease and/or repairing tissue. At this molecular-, or nano-scale, in the range of about 1 - 100 nanometers, biological molecular complexes form the basis of systems that provide structure, control, signaling, homeostasis, and motility in cells. There have been many advances in both the physical and biological sciences over the past several years that make nanomedicine research particularly attractive at this time. For example, new tools are being developed that permit imaging of structure, high speed measurement of the dynamic behavior of molecular assemblies, and measurement of forces at the molecular scale. These advances are complemented, on the biological side, by our knowledge of the human genome and a greater understanding of the molecular pathology of some diseases. Biologists have made stunning progress in describing complex phenomena at the cellular and subcellular level. However, large gaps remain in our knowledge about most of the physical characteristics of cellular components such as their exact quantities and variations, location, timescales, interactions, affinities, force generation, flexibility and internal motion. To the extent that measurements are possible, many remain cumbersome and cannot be applied to molecules inside living cells. Progress, using analytical models of molecular interactions already in hand, is stymied by this lack of information.

Research Scope

The NIH Nanomedicine Vision

The primary goal of this initiative is to characterize quantitatively the nanoscale components of the cell and to precisely control and manipulate these molecules and supramolecular assemblies in living cells to improve human health. As a first step, this initiative will define the information and capabilities that are needed to understand and precisely control cellular events at the nanoscale. Then, the capabilities will be developed and applied. New physical methods, instruments, and tools must be developed and applied to a variety of biological model systems. In addition, computational tools for data collection, storage, analysis and dissemination must be refined. More comprehensive models describing cellular structures and associations will be developed by using the knowledge gained from such precise quantitative physical measurements.

A second important aspect of this initiative is the recognition that the precise control required to manipulate cellular components will require the understanding and use of engineering principles. To this end, the approach will be informed by the design principles gleaned from the molecular processes and complexes found in living cells. In other words, biological tissues have evolved elegant, intricate pathways, molecular structures, and components at the nanoscale and there is a wealth of information in nature’s design. The long-term goal is to exploit these designs to repair intracellular structures at the nanoscale or build new structures for biomedical use. This knowledge will lead us to develop strategies, fabrication and manipulation methods to build nanostructures, assemblies, and systems that ultimately will lead to specific control of various individual cellular components in order to treat disease or repair damaged tissue.

What do we need to learn in order to engineer nano-sized components inside of cells? What types of measurements are lacking but, if made, could propel this effort forward? The following specific examples are presented to illustrate what we mean by physical, quantitative measurements that may be required to fill gaps in our knowledge. We are not suggesting these as topics of particular interest to this initiative or as areas that are any more or less in need than others, but as examples to convey the ideas presented above.

Protein-Protein Interactions. Knowledge of protein interactions is crucial for understanding the pathways and networks operating within and between cells. Collection of protein-protein interaction information on a genome-wide basis is now possible. However, most of the approaches available today fall short of gathering the needed information. Yeast two-hybrid measurements, for example, remove the protein-coding DNA sequences from the cells of origin and place them in an artificial environment. In doing so, subtleties of the actual intracellular behavior are lost as a consequence of this experimental manipulation. Cross-linking studies reveal only static information. The results are also not quantitative, for instance, with respect to binding constants. The next generation of tools will need to enable both qualitative and quantitative studies on the precise protein interactions in situ.

Intracellular Transport. The transport systems present in eukaryotic cells organize and move organelles within the cytoplasm, orchestrate and implement the distribution of replicated chromosomes to daughter cells, and are the basic machinery of cellular migration. Years of innovative research have generated detailed knowledge of the cellular organization and control of these dynamic systems. Mathematical models of their operation have been developed, but many key parameters, such as, rates of polymerization, nucleation, capping, or dissociation, must be estimated because they cannot be measured directly. Indeed, measurements central to the functions of these transport systems, such as stresses on the fibers, forces generated by assembly of the fibers or by interactions of fibers with the motors or other cellular structures, and force and dynamics of adhesion to substrates currently cannot be measured in vivo.

Biomolecular Dynamics. Often, measurements of molecular processes on a biologically relevant timescale are inadequate. For example, studies of second messenger signaling require harvesting tens of thousands of cells to measure significant changes of intracellular concentrations of relevant molecules. The methods require substantial time, at least on the order of seconds, before the first data points are measured. Is 10 seconds a rapid enough measurement? 5 seconds? Are studies with techniques that require such large quantities of material feasible or necessary for precision studies of nanoscale events? Is the information from these types of studies adequate to lead to the precision required for more refined, quantitative models? Clearly, a very different set of tools is needed to probe intracellular molecular events on the biologically-relevant timescales of milliseconds or microseconds.

These are just a few examples that typify the shortcomings in available knowledge and technology. A primary goal of the Nanomedicine Initiative is to stimulate development of radically new technologies that might provide novel strategies and new insights for cell biological studies of intracellular molecular activity.

Conceptual Framework for NDC activities

Initially, work at the Centers will determine what additional measurements and analytical and computational tools are needed to understand biological system design at the nanoscale. Next, the Centers will gather information from living biological systems and use the knowledge to engineer various molecular structures, assemblies, and possibly even organelles for treating diseased or damaged cells and tissues. We anticipate that reaching all of these goals may require ten years or more.

Each Nanomedicine Development Center will be formed around a specific theme that will serve as a model on which to focus studies of broader relevance. For example, a Center may choose a model system or pathway, such as a particular signaling pathway, a system of molecular motors, a proteasomal degradation pathway, an energy transduction system, or the transport of materials across membranes. Alternatively, a Center may choose a model cell type or disease. Regardless of the specific theme, the focus will be on the biological system and its relevance to health, not on the technological approach, per se, since several technologies will most likely be required to acquire the various physical data types needed to solve the biomedical problem. Nonetheless, the expectation is that the level of technology development in the Centers will be high.

Another emphasis of this program is to develop new tools and knowledge that can be generalized and therefore transcend any individual model pathway, intracellular assembly, cell type, or disease. Although work may begin with a single, well characterized model, effort should be devoted to developing tools for broader use than the individual model system or class of problem (e.g., cytoskeleton vs. signaling pathway vs. ion channels vs. machinery for replication, transcription or translation). Optimal measurement tools would be sufficiently generic that they would not need to be re-created for each molecule (e.g., today we must produce a GFP reporter construct for every gene and gene variant we wish to study or several constructs to conduct FRET studies of molecular rearrangements). Given this approach, the Nanomedicine Centers will need to collaborate on setting priorities and resource allocation with other NDCs, to maximize the resources and capabilities of the Centers. That is, each Center would not be expected to be comprehensive but would operate as part of a network so that new capabilities are generated efficiently and without redundancy.

A key to progress in nanomedicine is the development of multidisciplinary teams of scientists and clinicians who together will define the properties, knowledge, and concepts required by this initiative. These Centers will require collaboration by scientists from disciplines that may not typically interact with each other. For example, Centers might be populated with cell biologists, mathematicians, biochemists, engineers, molecular biologists, physical scientists, statisticians, etc. These multidisciplinary teams may propose solutions that challenge the assumptions held by more narrowly focused research groups. Such challenges are often required to achieve bold advances, and are invited by this initiative. Connections to the clinic are imperative; from the beginning of each center’s activity, the problems selected and the approaches to solution will be driven by medical needs.

National Network of Nanomedicine Development Centers (NDC)

In fiscal year 2005, four NDCs received five-year awards. Each is unique in its goals, expertise, and approaches, and all are committed to working in a collaborative effort to address the vision of this initiative and jumpstart the field of Nanomedicine. Applications submitted in response to this RFA should propose model systems, topics, diseases and medical targets, and approaches that are distinct from funded NDCs in the network. Potential applicants are encouraged to carefully examine the published descriptions of each funded NDC on the NIH Nanomedicine website (www.nihroadmap.nih.gov/nanomedicine/fundedresearch.asp) to be certain that your application will complement, and not overlap with, the directions and goals of these centers.

Center for Protein Folding Machinery (PN2EY016525)
Principal Investigator: Wah Chiu, PhD
Baylor College of Medicine

National Center for the Design of Biomimetic Nanoconductors (PN2EY016570)
Principal Investigator: Eric Jakobsson, PhD
University of Illinois, Urbana-Champaign

Engineering Cellular Control: Synthetic Signaling and Motility Systems (PN2EY016546)
Principal Investigator: Wendell Lim, PhD
University of California, San Francisco

Nanomedicine Center for Mechanical Biology (PN2EY016586)
Principal Investigator: Michael Sheetz, PhD
Columbia University, New York

Applicants may envision particular opportunities for collaboration or complementarity with funded NDCs. This must be expressed in both the concept approval letter (Section IV. Part 6 Other Submission Requirements) and the full application. NOTE: Letters of collaboration from awarded NDC Principal Investigators and other NDC key personnel will NOT be accepted.

Distinguishing the NIH Nanomedicine Initiative from Nanotechnology and other Initiatives

The primary focus of this program is to understand the intracellular physical properties of molecules and supramolecular complexes, i.e., cellular nanomachines, in order to provide the design principles that will lead to engineering of cellular targets for disease remediation. For example, the ability to construct vesicles for delivering antioxidants to an intracellular compartment may be a spectacular engineering achievement, but if done without considering affected regulatory pathways, immune reaction, applicability to other cells and tissues, and, the specific medical benefit, it would not be responsive to this initiative. It is essential, therefore, to have clear medical guidance and involvement of clinicians as applications are developed and throughout the award period. Additionally, while the goal is to remediate disease through the precise understanding and repair and/or control of cellular molecules and supramolecular assemblies, i.e., at the nanoscale, there is no requirement that any particular step in the investigation or development of solutions must involve nanotechnology. Nanotechnologies and tools to work at the nanoscale, however, will likely be essential to obtain the biological insights and for some aspects of subcellular manipulation.

Ongoing studies in cell biology and biophysics are rapidly advancing our understanding of cellular phenomena. Support under this initiative is not intended to supplement or replace support for such research but instead should depart from established, ongoing projects and propose truly novel approaches. These projects should break new scientific and technical ground for medical utility. This will require thinking out of the box that usually constrains the experimental plans that would be acceptable in most NIH grant applications. Plans are sought that entail various risk levels, including significantly higher levels of risk compared to typical NIH funded studies. While some of these plans will inevitably fail, some will succeed and are expected to radically advance the field. The award mechanism and management approach for this program will accommodate these bold projects.

Biocompatibility and Toxicity

There is awareness, in the scientific community and by the public, that nanoparticles and nanostructured surfaces may be highly reactive. This and other unique properties may bring great advances and capabilities but also may result in adverse effects on biological systems, whether in the human body or if released into the environment. Inherent within this initiative is the investigation of interactions between the materials and devices and biological tissues. Supported investigators will promote responsible handling and disposal of nanomaterials during the research. One of the primary goals of this initiative is to design particles, materials, and devices that can be used in vivo. As nanomaterials are synthesized or generated, toxicity and biocompatibility considerations must be addressed. The flexible funding mechanisms used for this initiative (including funds set aside for unique needs and out-year program increases) may be used to undertake additional research to focus on this important area.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the PN2 award mechanism. This mechanism is used to support Research Development Centers that will be available to qualified investigators without regard to the scientific disciplines or disease orientations of their research activities. The maximum award duration will be five years.

Other Transactions and use of Flexible Research Authority (FRA)

This NIH (PN2) is an other transaction award mechanism that is anticipated to operate under Flexible Research Authority (FRA). Congress granted the NIH Flexible Research Authority for certain NIH Roadmap initiatives including the Nanomedicine initiative so that staff, applicants, and awarded center personnel could maximize the program’s rapid development and success. FRA confers the following advantages:

• Encourages improved, extensive consultation with the research community during the planning process;
• Greater flexibility in evaluation and the peer review process;
• Expanded award authorities to facilitate collaborations; and
• Flexible resource allocation and re-allocation during the awarded project period since the directions and needs of an emerging field may change.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements. The scientific vision of the Nanomedicine Roadmap Initiative was conceived as a ten year plan. NIH Roadmap funding plans have been established only through 2010. It is anticipated that each Roadmap initiative will be evaluated for continuation after that date, and we expect that successful implementation of the Nanomedicine initiative will lead to continued support in the future.

2. Funds Available

On behalf of the NIH Roadmap, the National Eye Institute (NEI) intends to make two, three or four awards under this RFA. Applicants may request a maximum project period of five years. This RFA is a solicitation for additional centers that, with the four centers awarded in fiscal year 2005, will participate in the NIH Nanomedicine Network of NDCs.

Maximum awards for new centers funded under this RFA in FY2006 will be $1.4 million (total costs), which matches the first year funds for the NDCs awarded in FY2005. Thereafter, it is expected that a base amount of $1.2 million per year will be available for each center during the award period. Although the financial plans of NIH Roadmap provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of highly meritorious applications.

It is anticipated that new awards will begin on or before September 30, 2006.

In future years, additional program funds are expected to be available to augment the base amount of $1.2 million. The network of NDCs is awarded under Flexible Research Authority (Section II. Award Information) that uses modified peer review and flexible award management. Additional funds are anticipated to be available throughout the award period to potentially augment the base amount of $1.2 million. Approximately 15% of total program funds will be distributed to awarded centers based on emerging opportunities or needs among centers either for network resources or for individual NDCs. In FY 2008-9, program funds are expected to double. The increased funds may be used for scaling up operations, for additional centers, or for new initiatives identified by NIH staff in consultation with external consultants and the network investigators. Increased funds in FY2008-9 will be allocated based on competitive NDC budget requests, progress, new opportunities, and other network requirements as described in Section VI. 2A. Terms and Conditions of Award. Total amount of funds anticipated for the NDC network under this and prior solicitations is approximately $93.5 million.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

• For-profit or non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State and local government
• Eligible agencies of the Federal government
• Domestic Institutions/organizations.
• Foreign institutions are ineligible to apply but may collaborate with US institutions and may receive funding.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

2. Cost Sharing or Matching
Not applicable

3. Other-Special Eligibility Criteria

Individuals may submit one application as the Principal Investigator, but may be a co-investigator or consultant on other applications. Multiple applications from a single institution may be submitted.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

NOTICE - Prior approval is required before submitting applications in response to this RFA. Concept approval letters must be submitted by March 15, 2006. The primary purpose of the letter is to give NIH staff and reviewers an overview of the vision, goals, and approaches for an NDC, without requiring investigators to prepare costly, time-consuming proposals. Suggested content of the concept approval letter is given in Section IV.6. Other Submission Requirements.

Instructions for NDC Applications (Receipt Date: June 23, 2006)

Many aspects of the NDC application instructions differ significantly from standard NIH applications, so instructions found herein supersede the PHS 398 instructions. If not specifically addressed below, follow the PHS 398 instructions.

Administrative Information

Description, Key Personnel, Biographical Sketch, and Resources and Environment- Refer to p. 23-30 of PHS 398 Instructions, except Key personnel must appear in a separate table (see below).

Budget

Provide detailed budgets; do not use the modular budget format.

Funds are available to support two, three or four additional centers for up to five years beginning in FY2006. However, it is anticipated that 15% of the total Nanomedicine program funds will be set-aside for allocation within the network targeted to specific new opportunities, needs or deficiencies. When determining the center budget, assume a fixed base amount of funds available that does not include set-aside funds. First year funds available per center are $1.4 million, and $1.2 million is available in subsequent years. (See Section II.2 Funds Available).

You may submit plans for scale-up in FY2008 and FY2009, but no commitments will be made by NIH in the original award. Awardees will submit a detailed request in FY2007 that will be subject to additional review by NIH staff, external consultants, and possibly an outside review panel. Funds may also be partly used for additional centers or complementary studies.

There are no specific budgetary requirements for the percentage of work required in the funded institution relative to consortia or subcontracts.

Page Limits

Appendix consists of no more than 10 publications limited to accepted manuscripts not already in print or on-line as of the date of submission. Appendix hard copies will not be accepted. Submit appendix material as PDF files on a CD-ROM (see Section IV.3.B Sending an Application to the NIH). Any figures or photos must be included as high quality images in those PDF files. No printed copies will be sent to the review team.

Research Plan

NOTE: Applications will not be reviewed unless each lettered section headings (A H below) and appropriate contents are included in your application. Your NDC application must be self-contained. Reviewers will not be given copies of your concept approval letter so it would be valuable to reiterate and elaborate on your Nanomedicine Challenges and your ideas related to Nanomedicine: Unique and Distinct expressed in your concept approval letter (see Section IV.6 Other Submission Requirements). The ways in which the proposed center would complement and be synergistic with the existing NDCs must also be included here.

A. Introduction, Vision, Background, and Significance

You should incorporate the following information in this section:

• Theme of the proposed Nanomedicine Development Center.
• Model system: why is it a good one in which to develop new tools and concepts?
• What is the physiological or medical relevance of the system?
• What information is lacking for a quantitative description of the system?
• What tools are in place and what additional ones will be required to achieve the aims?
• How will you generalize the new tools and concepts to other systems?
• What biological design principles will be elucidated?
• How will that information be applied to developing the medical therapeutics?

B. Published Work, Studies in Progress, and Research Expertise

Summarize the research for which you are currently funded (or pending) through conventional mechanisms its rationale, methods and anticipated endpoints that are relevant to the proposed project. This includes the biological goals, the data sets, and the tools that you are currently developing. Describe your team’s expertise and include any relevant information to demonstrate your capabilities, interactions, and collaborations. You should refer to your Table of Key Personnel where appropriate (see E. Center Structure).

C. New Studies and New Directions

The NIH Roadmap Nanomedicine Initiative is conceived as a ten-year plan working toward engineering nanoscale cellular components for human health and medical practice. Although your NDC application will request funds for a five-year period, it is important to maintain the perspective that the vision and goals of the program are geared to at least a ten year development period. In the first five years, you are not expected to complete the entire sequence from developing new tools, making novel measurements and developing engineering-level understanding of biomolecular systems, to ultimately developing novel medical treatments. When describing your studies, refer to your expectations about where you realistically expect to be after five and ten years. The five-year timeline should be more detailed and linked to the research plan.

This is the section where your bold new initiatives should be discussed.

• How are your proposed studies different from ongoing projects in your laboratory and in labs of others in the field?
• What novel endpoints would be achieved in comparison with the studies described in the previous section?
• Describe the new studies that will be initiated because of the unique team that has coalesced.
• Specify the levels of risk of the proposed work, and justify those statements.

The following may help to guide your thinking on issues to address in this section:

What data/data types are missing, either because we had not realized they were needed (because we were not asking the question from the perspective of system design) or because we do not have the tools to measure them? Which of these are your initial targets; why have you chosen them?

As previously stated, the purpose of the NDC is not to supplement or accelerate ongoing research that will yield immediate results. You may think of the NDC as a way to develop the tools and approaches you will need five years from now. However, initial work at your NDC may depend on a few key issues related to your ongoing work. If so, identify those issues and justify why you must use NDC funding to accelerate that research so that you will be in a position to proceed with the goals that are central to the NDC.

Propose plans for higher-risk studies. What are the levels of risk and nature of risk of various components? Justify the need for this research (i.e., describe the high pay-off) and present a rational scientific basis for your plan to achieve the goals. Although there is no specific requirement for preliminary data in this application, you must present a plausible flow to your reasoning. Use any combination of preliminary data, published work, theory, mathematical reasoning, and clinical relevance to guide your thinking.

Identify key scientific and technical hurdles, options for overcoming them, and alternative approaches. What will be the impact of failure to achieve some of the goals?

For these new studies, describe dependencies such as data that must be collected or tools that are needed before the proposed studies can be done. Distinguish between short-term and long-term studies.

Include a timeline of activities to outline how the project's goals can be met within the time frame of a five year NDC award. The timeline will also assist the investigators and NIH in evaluating progress toward the project's goals. If appropriate, explicit, quantitative milestones should be presented.

Center and Network Organization

D. Resources

The ongoing research described in section B (above) is being done with other support. Document the resources available at the participating institutions and the enhanced capability of your center because of association with other centers or technical cores available to your NDC.

• How will the ongoing projects be enhanced by work at your NDC and vice versa?
• What resources are in place or need to be developed locally?
• How will you use nanotechnology and other resources that are available nationally?
• Do you have agreements in place for access to other facilities?

E. Center Structure

Table of Key Personnel

Include names, degrees, institutional affiliation, and expertise. Letters of collaboration must be included for all team members listed (see below; Section M. Key Personnel and Consultant Letters ). Only key personnel should be included. Post-doctoral fellows, graduate students, technicians should not be included unless they are contributing to the intellectual development of your application or are essential for their particular expertise in completing proposed studies.

• Investigator interactions
• Core facilities (if appropriate)
• Management structure and plan.
• Scale-up plan. As stated above, you only need to broadly state the expected use of additional funds in FY2008 and FY2009. If appropriate, refer to studies proposed in Section C, New Studies and New Directions . For example, are additional funds needed for high throughput, generalization to other systems, anticipated new directions that depend on earlier work, etc.? In FY2007, detailed plans from awarded NDCs will be required.

NIH is not specifying a particular organizational structure for a NDC. However, note that the effectiveness of the proposed structure will be a criterion of the evaluation prior to an award, and its successful implementation will be monitored after an award is made.

The application should describe the specific administrative and organizational structure that will be used to support the research, and the synergies enabled by this structure. These plans will take into account that NDC projects will be multidisciplinary and will draw on a variety of resources. If core facilities or shared resources are required, describe their management and service to the research projects at your NDC. Explain how different components of the organization, such as key personnel, will interact, why they are essential to accomplishing the goals of the research, and how the combined resources create capabilities that are more than the sum of the parts. Present evidence that the investigators can collaborate effectively. "Centers-without-walls" are welcome under this solicitation.

The Principal Investigator or leadership team is responsible for developing and managing a decision-making structure and process for resource allocation, i.e., a management plan. This is particularly important, as NDCs are expected to pursue some high-risk/high-payoff strategies, and therefore, must have in place the means to evaluate progress frequently and to balance and re-balance funds and other resources. Although no specific percent effort is specified, a good management plan will require significant commitment of key personnel.

F. Network Structure

Center Interactions. Describe how your NDC will interact with the other NDCs in the network. What administrative and scientific contributions will you make to the network, and what do you need from a network for your NDC to be successful? Specify potential collaborative studies between your NDC and others within the network.

Assurances

G. Human Subjects and Animal Welfare

Unlike traditional five-year grants, the extent of your studies and the scope of your project may be uncertain. Many specific experiments are not expected to be described in complete detail in your application so that required approvals by Institutional Review Boards (IRB), for studies with human subjects, and/or by Institutional Animal Care and Use Committee (IACUC), for animal studies, cannot realistically be completed by the time of award. No approvals are required at this time and completion of the Human Subjects and Vertebrate Animals sections are not required in your NDC application at this time. If you do not identify specific studies you may check No on the application face page for human or animal subjects. Awards will be issued with restrictions that require IRB, IACUC and NIH approval, prior to any work with humans or animals. NIH approval may require additional external review before restrictions are lifted. After the award is made, you will need to submit a more detailed research plan when human subjects or vertebrate animals are used that must comply with all relevant policies in accord with the instructions in the 398 application form (http://grants.nih.gov/grants/funding/phs398/phs398.html). Refer to Section VIII. Required Federal Citations.

If you propose specific experiments involving human subjects or vertebrate animals at any time during the proposed project period, either at the applicant organization or at any other performance site or collaborating institution, then you must answer Yes for Human Subjects and/or Vertebrate Animals on the application face page, even if you expect that the human subject research will be exempt from regulations for the protection of human subjects. Before commencing work using human subjects or vertebrate animals, all assurances for safety and proper treatment and handling must be in place and must comply with standard regulations (See Section VIII. Required Federal Citations).

H. Biohazards, Toxicity and Biocompatibility

If your short-term goals include using or developing nanomaterials, the following are required:

1) Include a plan that describes your approach to assessing the toxicity and biocompatibility of nanostructures created by your research. There are currently no specific NIH guidelines available so it is your responsibility to devise an effective plan, consistent with regulations of your institution, to address these issues.

2) Submit a plan that describes your procedures for safely handling these potentially highly reactive particles. This plan must be cosigned by your institutional safety officer.

3) Submit documentation indicating that all lab personnel have completed an annual hazardous materials safety course.

Inadequate plans or documentation may require a restriction on awards until plans are approved by NIH.

Other Items

For information on the following, refer to p. 35 of the PHS 398 Instructions

I. Literature Cited

J. Consortium/Contractual Arrangements

K. Data and Resource Sharing (See Section IV.6 Other Submission Requirements)

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Award Criteria.

L. Suggested Reviewers and Expertise

Technical experts will be recruited to participate in the review of the NDC applications. You may suggest reviewers as examples of individuals with the type of expertise appropriate to assess the merit of your application. Organize your list in outline form by areas of expertise. Include the investigator’s name and institution. NIH staff will have the primary responsibility in assembling the panel.

M. Key Personnel and Consultant Letters

Include letters from all individuals confirming their participation and describing their roles in the project. If any are paid consultants include rate/charge for consulting services.

Do not place these letters in the Appendix.

N. Appendix

• Do not use the Appendix to circumvent the 35 page limit of the research plan. An NDC application that does not observe these limitations will be returned.
• Submit as files in PDF format on a CD-ROM.
• Up to 10 manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.
• Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.

Photographs, color images, must be included in the Research Plan. If you wish to include movies, a placeholder should be included in the Research Plan, and the movie may be submitted on a CD-ROM directly to the NEI.

O. Checklist (Refer to p. 36 of the PHS 398 Instructions)

Foreign Organizations

Although foreign organizations are ineligible to apply, the following may be relevant if a foreign collaborator is included on the application:

Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11."
• Funds for up to 8% administrative costs (excluding equipment) can now be requested (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html)
• Organizations must comply with federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with federal/NIH biosafety and biosecurity regulations. See Section VI. 2. Administrative Requirements, "Terms and Conditions of Award".

Proposed research should provide a unique research opportunity not available in the U.S.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Concept Approval Date: March 15, 2006
Approval Notification Date: April 17, 2006
Letter of Intent Receipt Date: Not applicable
Application Receipt Date(s): June 23, 2006
Peer Review Date: July-August 2006
Council Review Date: September 2006
Earliest Anticipated Start Date: September 25, 2006

3.B. Sending an Application to the NIH

1 Concept Approval Letter Receipt Date: March 15, 2006

Submit directly to:

Dr. Richard S. Fisher
NIH Roadmap Nanomedicine Initiative Project Team Leader
National Eye Institute
5635 Fishers Lane MSC 9300
Bethesda, MD 20892
(FEDEX/UPS/DHL address: Rockville, MD 20852)
Telephone: (301) 451-2020
FAX: (301) 402-0528
Email: [email protected]

Approval letters must include the email address of the Principal Investigator.

Note: Email submissions of the Concept Approval Letter are acceptable and preferred. You may submit a PDF copy of your concept letter to Dr. Richard Fisher by email ([email protected]).

For email submissions, please use the subject line: Nanomedicine Concept Letter. Receipt of your concept letter will be acknowledged by email.

2 Application Receipt Date: June 23, 2006

Potential applicants will be notified by April 17, 2006 whether or not the NEI will accept an application for a NDC.

If the NEI is willing to accept assignment of an application for consideration of funding, the staff will notify the Center for Scientific Review before the application is submitted. The Principal Investigator must include a cover letter with the application that includes a copy of the email notification indicating that the NEI will accept the application.

Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Dr. Richard S. Fisher
NIH Roadmap Nanomedicine Initiative Project Team Leader
National Eye Institute
5635 Fishers Lane MSC 9300
Bethesda, MD 20892 (FEDEX/UPS/DHL address: Rockville, MD 20852)
Telephone: (301) 451-2020
FAX: (301) 402-0528
Email: [email protected]

NOTE: It is preferred that applicants submit the additional copy and appendix materials as PDF files on a CD-ROM. Appendix materials should appear in a separate directory on the disk. Noted above

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the National Eye Institute. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
These awards are other transactions (Section II. Award Information and Section VI.2.A) and various terms of Flexible Research Authority that appear in the Notice of Award may supersede the NIH Grants Policy Statement.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

Awards will be issued restricting the use of humans or animals until all IRB and IACUC approvals are submitted and protocols are reviewed and approved by NIH staff (See Section IV.2 Content and Form of Application Submission).

6. Other Submission Requirements

Concept Approval Letter (Receipt Date: March 15, 2006)

NEI approval is required in order to submit an application. Applicants should submit their vision for a Nanomedicine Development Center, and a brief summary of the set of problems the center might try to solve and approaches to do so. The primary purpose of the letter is to give NIH staff and reviewers an overview of the proposed vision, goals, and approach, without requiring investigators to prepare costly, time-consuming proposals.

This vision should begin with the concepts described in this RFA, and develop them based upon the applicant’s understanding of the science, the technology, and the medical needs. The applicant may also propose a structure for the proposed center. Projects that would overlap significantly with funded NDCs will not be acceptable; projects that complement and are synergistic with funded NDCs are highly desirable. Applicants may choose to address the following in a letter of five pages or less:

Nanomedicine Challenges

• Articulate the Nanomedicine challenges in your chosen area of investigation in the context of this initiative.

Goals and Approaches

• Describe the model system(s) you will investigate.
• What are the short term goals, and approaches you will use to obtain quantitative measurements in your model system(s).
• Describe what underlying engineering principles will be revealed?
• Describe how the tools and results can be generalized to other biological systems.
• How will completion of the short-term goals position you and others in the community to address a specific medical problem?
• What are the longer-term goals?
• What are your goals for providing progress toward medical benefit over ~10 year period? If you are successful, what do you hope to build and how will it be used for diagnostics, treatment or repairing tissue?

Nanomedicine: Unique and Distinct

• State how the proposed goals, approaches, and collaborations are distinct and higher risk, from the research that you and members of your team have been pursuing under other support. Nanomedicine is not simply cellular biophysics or protein engineering. Distinguish your approach to Nanomedicine from these and other disciplines. (Example: Traditional protein engineering has been done on well-defined/constrained proteins. It doesn t account for dynamic states or cellular environments. Research in the NDC will do both of those.)
• State how your project, in the context of the network of current awardees, contributes to the goal of stimulating the development of the emerging field of Nanomedicine.
• Describe synergies, complementarities, and unique collaborative opportunities with other NDCs in the network.

Collaborators

• Identify your key collaborators and areas of expertise for your NDC.

References

In addition to the five page letter, a list of literature citations may be included.

The NEI will use the concept approval letter to determine if the applicant should submit a full application. Approval will be sent by email on or before April 17, 2006. A copy of this email should be included in the cover letter to CSR that accompanies your full application. Concept approval letters must include the email address of the Principal Investigator.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Participation in the Nanomedicine network of NDCs will require submitting a plan for managing intellectual property (IP). Awarded NDCs are developing communication, data and resource sharing tools to promote extensive information exchange and collaborative efforts. The IP plan is not required as part of this application but must be submitted prior to receiving an award. After the review of these applications, instructions for preparing an IP management plan will be sent to applicants who are likely to receive an award.

Section V. Application Review Information

1. Criteria

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of program priorities

Flexible Research Authority (Section II. Award Information and Section VI.2.A Terms and Conditions of the Award) applies to the review of these applications. NDC applications will be evaluated in accord with the criteria listed below. Centers will be awarded based on these criteria and project team assessment of NDC integration in the network. The five main review criteria, Significance, Approach, Innovation, Investigator, and Environment, form the basis for evaluating peer-reviewed applications at the NIH. They are tailored here specifically for the NDC applications and are supplemented by additional criteria (given below).

The relative weight of the five criteria will not be specified and will be assigned as reviewers deem appropriate. However, Innovation and Investigator (i.e., the track record of the PI and leadership team for solving difficult technical and conceptual problems) will receive substantial attention in the review of these applications.

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NEI in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does it encompass the elements of the NIH Nanomedicine vision? Does it generalize its vision, concepts, approaches and measurements to other model systems and diseases? If successful, will this center create something new that would not have been achieved without the Nanomedicine Initiative?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Is the applicant reaching beyond the safe, guaranteed work? Are new studies proposed that are more than simply an expansion of ongoing work? For the riskier, but potentially high-payoff components, are the scientific bases of the plan, and the elements of science and technology, where there may be knowledge gaps, clearly described? Are the performance criteria for declaring success adequately explained and justified? Is there a plan for evaluating progress and deciding when a project should be terminated or re-directed? Is there evidence of a multidisciplinary approach?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Does it propose to develop new measurement capabilities that enable important measurements that we either cannot make now, or can make only with difficulty?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Do the Principal Investigator and other key personnel have the experience to manage the NDC? Do members of the leadership team have a track record of having solved difficult technological or conceptual problems? Have the necessary personnel been recruited for the proposed multidisciplinary studies? Is there evidence that the team, or a subset of the team, has worked together productively in the past? Are there adequate plans to achieve smooth and efficient collaboration, and to share and allocate resources effectively?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? Is there a plan to integrate effectively other (institutional, regional, national, international) resources that augment those available directly to the participating investigators?

Additional Criteria:

• Does the applicant describe the medical relevance or eventual application to medical needs? Is there evidence that the project is driven by curing disease and/or repairing tissue?
• Is the effort proposed for the NDC clearly delineated from the effort of ongoing, funded (or pending funding) research?
• Will the proposed NDC complement the existing NDCs and add significant value to the network?
• Will the center identify new, quantitative knowledge of the biological systems?
• Has the applicant enumerated the specific knowledge gaps that would be filled?
• Is there a description of the new quantitative measurement capabilities that would be developed?
• Is there a plan for developing new, or enhancing current, mathematical models?
• Does the applicant relate the approaches and the novel measurements to specific gaps in knowledge of biological design or to key parameters of the mathematical models being developed?
• Is there a discussion of potential engineering principles associated with, or that could be applied to, Nanomedicine?
• Does the applicant justify how data quality and measurement uncertainties would be addressed and how that would affect quantitative modeling?
• Does the applicant propose to make novel measurements in living cells?
• Are timelines and appropriate milestones clearly defined and realistic?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

NOTE: Participation of in the National Nanomedicine Network of Nanomedicine Development Centers indicates willingness to associate in a highly cooperative and collaborative network. Sharing research data and resources would be expected to be significantly greater than typically expected.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 unless superseded by Flexible Research Authority (see below).

Nanomedicine Development Center Awards Terms and Conditions

This award provides support for Nanomedicine Development Centers (NDC) that participate in the NIH Nanomedicine Development Center Network (NNDCN). THIS AWARD IS FUNDED BY THE NATIONAL INSTITUTES OF HEALTH THROUGH THE NIH ROADMAP FOR MEDICAL RESEARCH. Any publications or other acknowledgements should indicate that "This work was funded by the National Institutes of Health through the NIH Roadmap for Medical Research . Information on the Nanomedicine Roadmap can be obtained from http://nihroadmap.nih.gov/nanomedicine. Support for the NIH Roadmap initiatives is provided by all Institutes and Centers. The National Eye Institute (NEI) is the administrative institute for the Nanomedicine Initiative.

Flexible Research Authority (FRA)

The NIH policy for research supported under this award will be governed by Flexible Research Authority contained in the P.L. 108-447, CONSOLIDATED APPROPRIATIONS ACT FOR FY 2005:

SEC. 217. (a) AUTHORITY.--Notwithstanding any other provision of law, the Director of the National Institutes of Health may use funds available under section 402(i) of the Public Health Service Act (42 U.S.C. 282(i)) to enter into transactions (other than contracts, cooperative agreements, or grants) to carry out research in support of the NIH Roadmap Initiative of the Director.

(b) PEER REVIEW.--In entering into transactions under subsection (a), the Director of the National Institutes of Health may utilize such peer review procedures (including consultation with appropriate scientific experts) as the Director determines to be appropriate to obtain assessments of scientific and technical merit. Such procedures shall apply to such transactions in lieu of the peer review and advisory council review procedures that would otherwise be required under sections 301(a)(3), 405(b)(1)(B), 405(b)(2), 406(a)(3)(A), 492, and 494 of the Public Health Service Act (42 U.S.C. 241, 284(b)(1)(B), 284(b)(2), 284a(a)(3)(A), 289a, and 289c).

In accord with the authority specified above in Section 217 (a), awards to support the NDCs will not be considered contracts, cooperative agreements or grants. However, funds will be disbursed using a standard NIH Notice of Grant Award. The administrative and funding instrument used for this Nanomedicine program will be the PN2 mechanism. This is a new mechanism developed specifically for this new type of transaction to fund Nanomedicine Development Centers using FRA. PN2 Nanomedicine Development Centers will operate within the NIH Nanomedicine Development Center Network (NNDCN also referred to as the network ).

Under the PN2 award mechanism, 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. Project management will include set-aside funds and will include allocation of funds as specified below (see Allocation of Funds).

NIH Staff Responsibilities

NIH oversight will be governed by the NIH Nanomedicine Initiative Project Team (NIPT) which will have substantial scientific-programmatic involvement. The role of the NIPT will be to facilitate and coordinate but not direct activities. The NIPT will consist of representatives of at least 8 NIH institutes and centers and will be chaired by a Project Team Leader. The Project Team Leader will be the point-of-contact for the Principal Investigator of each NDC. The NIPT will:

• Assist in avoiding duplication of effort across awardee projects.
• Help coordinate collaborative research efforts that involve multiple awardees within the NNDC network.
• Review and approve critical stages in the research program before subsequent stages are implemented.
• Assist in the interaction between the awardee and investigators at other institutions.
• Be a voting member of the Steering Committee and its subcommittees (one vote).
• Help the Steering Committee develop and draft operating policies and policies addressing recurring situations that require coordinated action where necessary.
• Review the scientific progress of the individual awards for compliance with operating policies developed by the Steering Committee, and may recommend to the NIH to withhold support, suspend, or terminate an award for lack of scientific progress or failure to adhere to the terms of the award and/or the policies established by the Steering Committee.
• Determine resource needs and direct the re-allocation of set-aside funds.
• Determine a review process and decision process for scale-up funds in FY2008 and FY2009.
• Recommend, in consultation with the Scientific Advisory Panel (see below), additional research endeavors within the constraints of the approved research and negotiated budget.
• Advise on the integration of additional centers into the NNDCN in FY2006.
• May consult with other NIH staff as well as non-NIH experts in the field in order to carry out these responsibilities.
• Be responsible for any other programmatic activities typically undertaken by NIH program if not otherwise specified above.

In addition, the NEI will designate an Other Transaction Management Contact to provide fiscal and administrative oversight of this award.

Principal Investigator Rights and Responsibilities

The Principal Investigator will coordinate project activities scientifically and administratively at the awarded institution, including research design and protocol development, data collection, quality control, data and safety monitoring plan for any studies involving human subjects, final data analysis and interpretation, and preparation of publications. The Principal Investigator will have the primary responsibility for defining the details for the projects within the guidelines of this RFA and for performing all scientific activities. The Principal Investigator will be responsible for collaborations between his/her NDC and the NNDCN. The Principal Investigator will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described below. Specifically, the Principal Investigator will:

• Determine experimental approaches, design protocols, set project milestones, and conduct experiments.
• Analyze and interpret research data.
• Release data according to the approved plans for timely sharing of research resources and data generated through the award, and publish results, as agreed upon by the Steering Committee.
• Establish and maintain a public web site to disseminate timely information concerning the goals and progress of the center.
• Establish such internal advisory committees and processes as may be needed to provide scientific and administrative oversight. Minutes of these internal advisory meetings will be made available to the NIPT upon request and may be available to the Scientific Advisory Panel.
• Serve on the Steering Committee.
• Provide information to the NIPT concerning progress by submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and the Scientific Advisory Panel.
• Accept and implement all scientific, practical, and policy decisions, common guidelines and procedures approved by the Steering Committee and Scientific Advisory Panel.
• Share facilities, research resources, tools, and data of interest to those facilities with other awardees, as directed by the Steering Committee and the Scientific Advisory Panel; share standardized information on new developments and/or methods for solving obstacles with the investigators funded through this initiative and with the NIPT.
• Prepare for annual site visits by NIPT for programmatic and/or administrative purposes.

Awardees will retain custody of and have primary rights to the data, software, and tools developed under these awards subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

Collaborative Responsibilities

Steering Committee (SC)

The NIPT and Principal Investigators of the NDCs under this RFA will be responsible for forming a Steering Committee as defined below. The Steering Committee will act as the main governing board that will review the progress of the research activities, develop collaborative protocols, identify technological impediments to the progress, select strategies to surmount them, and identify opportunities for sharing techniques and tools developed within each individual project and each center within the network. The Steering Committee will:

• Optimize the flow of information and communication within the network.
• Play a key role in standardizing data collection, reporting, and generalizing across the network.
• Be instrumental in disseminating research results within the network and into the public domain.
• Monitor developments of external programs at other nanotechnology and Nanomedicine centers as they may relate to the NIH NDCs.
• Advise the NIPT of scientific developments and opportunities that may enhance the goals of the program.
• Help to develop uniform procedures and policies for the governance of the NDCs .
• Provide input and recommendations to NIPT with respect to allocation of set-aside, re-allocation and/or redistribution of resources as implemented under FRA.
• Monitor, develop, and implement quality control procedures that assure consistency across Centers.
• Serve as a venue for coordination on improving the state of the art, for example by reporting progress, disseminating best practices and collectively evaluating new procedures, resources, and technologies.
• Be responsible for coordinating NDC efforts within the network and serve as the primary means of interaction with the NIPT. Schedule meetings and conference calls as necessary.
• Determine frequency and need for meetings with wider participation of more of the research staff from each NDC. Monitor all aspects of arrangements and content of these meetings.
• Provide information and guidance to NDC personnel with respect to NIPT award management and use of FRA in implementing the goals of the NIH Nanomedicine initiative
• Develop a plan for terminating projects that become unpromising or unproductive.
• Meet with the SAP as described below.

The Steering committee will consist of the Principal Investigator (or designated alternate) from each NDC and one or more members of the NIPT. Each center will be required to participate in all official steering committee meetings. The Principal Investigator from each project will have one vote and the NIPT will have one vote. The Steering Committee may, as it deems necessary, invite additional, non-voting scientific advisors to meetings at which research priorities and opportunities are discussed.

There will be two meetings of the Steering Committee in the first two years and at least one meeting per year in the following years. The first meeting of the Principal Investigators funded under this RFA will be a Planning Meeting in the Bethesda, MD area soon after awards are issued. At the first Steering Committee meeting the members may: (a) draft a charter to detail policies and procedures and develop a process for monitoring compliance with the policies and procedures and for recommending that the NIPT act on evidence of non-compliance with Steering Committee policies; (b) agree upon the terms of the charter; (c) discuss the approaches that were proposed in the project applications and any relevant new information, and set initial priorities for the projects to be pursued; and (d) develop procedures and policy for determining progress and support for projects, especially high risk projects that may take longer to come to fruition but are important to further the goals of the program.

Scientific Advisory Panel (SAP)

The Scientific Advisory Panel (SAP) will be responsible for reviewing and evaluating the progress of the awardees toward meeting their individual and collective goals. The SAP will provide recommendations to the NIPT about continued support of the individual projects and the group of projects awarded. The SAP will be composed of senior scientists with appropriate scientific knowledge and experience, who are not NIH extramural program staff or associated directly with any of the NDCs, who will be selected by the NIH program staff. The SAP will provide scientific, technical, and budgetary advice to the NIH. The membership of the SAP may be enlarged permanently, or on an ad hoc basis, as needed. The SAP will meet at least once a year and will be attended by at least one NIH official. Meetings will be held either at NDC institutions or NIH. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the Scientific Advisory Panel members to interact directly with the awardees. No supplementary funds are expected to be available for NDC investigators to travel to these meetings. At least annually, the SAP will make recommendations regarding progress of the individual and collective group of projects and centers and provide advice to the NIPT about changes, if necessary.

Dissemination of Research Results

This initiative encourages investigators to facilitate translating effective interventions and tools into practice. As part of the NIH commitment to the rapid translation of research evidence into practice, plans to disseminate research results into practice, negotiated at the time of award, will become a condition of the award.

Intellectual Property Management Plan

An intellectual property management plan will be submitted prior to issuing an award. The plan will be evaluated by NIH staff and may be negotiated before award. Upon acceptance, the plan for managing Intellectual Property (IP) will be considered a component of the official grant file and shall serve as the minimum acceptable requirement and as a condition for continued funding. The applicant is encouraged to adopt additional practices that facilitate the progress of the center and the Network of Nanomedicine Development Centers. Additional NIH staff review of the IP management plan may require awardees to revise the submitted plan for continued funding.

Terms and Conditions of the PN2 Award under FRA

The NIH Grants Policy Statement (rev, 12/2003) references terms and conditions for grants that apply to PN2 awards except as noted in this award document.

Non-competing continuation applications should be submitted using the PHS 2590 http://grants.nih.gov/grants/funding/2590/2590.htm (rev. 9/2004). Recipients are to prepare a complete PHS 2590, including a detailed budget. Additional details on the requirements for the progress report will be distributed to the PN2 award recipients after the awards have been issued.

Carryover of Unobligated Balances

Use of unobligated balances is restricted and carryover of unobligated balances from one budget period to the next requires NIH awarding office prior approval.

Program Income

Program income earned during the period of support is subject to the deductive alternative.

Center and Network Award Management

As outlined in this document, especially given the wide latitude of FRA, the network of centers will work closely with NIH staff and a Scientific Advisory Panel in those aspects of scientific and technical management of the project as described below.

Meetings of the network Steering Committee and Scientific Advisory Panel will be primarily scientific in nature, to share information about progress, identify and facilitate potential collaborations, and share information about emerging concepts and resources. The meetings will also be a focal point for monitoring progress, exploring new scientific opportunities, and evaluating the current and future investment of initiative funds. The meetings will facilitate the collaborative nature of a network of centers. Meetings for wider participation of more of the research staff of each of the NDCs, and other interested parties, will be coordinated with the steering and advisory committee meetings.

Since Nanomedicine is an emerging field, the directions and needs of the field will develop with time. Examples of such needs that the network will address include, but are not limited to topics described above, e.g., human and animal subjects; laboratory safety and materials disposal; ethical, legal and societal dimensions; and resources development and sharing.

Allocation of Funds

Flexibility in award management is considered an integral part of the use of FRA. A process will be established to evaluate NDC proposals for using set-aside funds (see below). At least once each year, NDC proposals will be presented to the Steering Committee by each of the NDC Principal Investigators. The Steering committee will provide recommendations to the NIPT for allocating funds. The NIPT will determine resource allocation with additional input from the Scientific Advisory Panel, if required. Because more risk will be accepted in the development of the NDC research plans, there may be a need to terminate all or part of a particular avenue of research. The goal is to balance risks with benefits and make adjustments during a project so that termination of awards is unnecessary. NIH will work with the Steering Committee and the SAP to assess progress and develop alternatives to modify research plans if progress is insufficient. The proposal format and requirements will be developed and may change as the program progresses. Similarly, proposals for scale-up funds that are available in FY2008 and FY2009 will be presented to the Steering Committee, which, in turn, will provide recommendations to the NIPT.

The association of centers in a network provides an opportunity for wider influence on center activity. Oversight committees and NIH staff will play an important role in monitoring progress at individual centers while still encouraging independence and creativity. There are several possibilities that might require intervention and re-allocation of resources. For example:

• A project might require resources that were not anticipated either to break through an obstacle to success or, alternatively, because the project is a great success.
• Individual projects may be failing with little or no hope of success. This could be for a variety of reasons. For example, maybe a project is not clearly articulated because the technical path is not obvious. Each center will have its own process for evaluating progress on projects, regardless of the risk level, and should make decisions about when to discontinue projects that are not working. Centers will report on such decisions, which will also be discussed by the network advisors.
• Even though a project appears promising, it may be determined that progress is too slow (e.g., there may be other technologies required to advance the work), and therefore, the limited resources of this program will have to be used in other ways.
• A project may be making good progress, but may be conventional and therefore eligible for funding by standard grant mechanisms outside this program.

The network will strive to achieve a balance between funds that each center can rely upon to maintain its core activities and funds that are set aside to meet emerging needs. In year one, procedures will be developed to allocate the set aside funds for years 2-5, using evaluation criteria appropriate for the particular purpose.

Estimated Nanomedicine Initiative Funds ($ Million)

Allocation of funds is subject to availability of funds, number of centers awarded, and network resource requirements.

Funds Allocation Scheme - FY2006

The following presents one model among other possible models that may be adopted. It assumes that four additional NDCs may be awarded beginning in FY2006, increasing the total number of centers in the network to eight.

Individual NDC award amounts are stated below. Allocation and management of funds will remain flexible throughout the project. A process will be developed to apply for, and evaluate proposals to use set aside funds at least once each year. Set aside funds (approximately 15% of total available to the initiative for NDCs) will be awarded for a maximum term of one year and will not be considered part of the center’s base award. More frequent evaluation may be required as the program develops.

Approximately $5.6M (total costs) of the Nanomedicine initiative funds are available for up to four additional NDCs ($1.4M per center) to join the network.

Funds Allocation Scheme FY2007-2010

Although the outline here is specific, it is subject to change and may evolve based on the needs of the individual centers and network and availability of funds in accord with Flexible Research Authority.

Assuming that the NDC network consists of eight NDCs, these centers will likely be awarded approximately $1.2M per year and compete for set-aside funds.

In fiscal year 2007, set aside funds of $1.8 million are eligible for centers and for network resources.

In FY2008 and 2009, it is anticipated that an additional $13.0 million will be available for scale-up of some or all centers on a competitive basis, or to add new components to the program. A process to apply for those funds and evaluate those requests will be established in FY2007.

3. Reporting

Progress Reports. NDC Principal Investigators may be required to produce more detailed annual progress reports than are required for an NIH grant. NIH staff may require other reports periodically as a consequence of meetings of the Network committees, or other NIH requirements (e.g., related to FRA, etc.). Formats for these reports will be provided, and may change as the needs of the program evolve. NIH staff and the Scientific Advisory Panel members will receive these reports and may elect to share some or all of any report with the other NDCs within the network. Progress Reports must contain information on activities for the sharing of research resources and intellectual property.

NIH Oversight. There will be significant involvement of NIH staff (NIPT) and external advisors (SAP) throughout the project period. Oversight involves examining whether adequate progress is being made using valid reasoning and approaches. Traditional NIH oversight involves program and grants management staff of the funding institute. Because Nanomedicine is multidisciplinary and the science is relevant to the missions of most or all the NIH institutes, NIPT oversight may include program staff from other NIH institutes that may not have NIPT representation. The NIPT will determine, in consultation with the NDCs and the network advisory committees, whether progress is satisfactory and whether resources should be redirected.

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Dr. Richard S. Fisher
National Eye Institute
5635 Fishers Lane MSC 9300
Bethesda, MD 20892
(FEDEX/UPS/DHL address: Rockville, MD 20852)
Telephone: (301) 451-2020
FAX: (301) 402-0528
Email: [email protected]

2. Peer Review Contacts:

Dr. Richard S. Fisher
National Eye Institute
5635 Fishers Lane MSC 9300
Bethesda, MD 20892
(FEDEX/UPS/DHL address: Rockville, MD 20852)
Telephone: (301) 451-2020
FAX: (301) 402-0528
Email: [email protected]

3. Financial, Other Transactions, or Grants Management Contacts:

William Darby
Grants Management Officer
National Eye Institute
5635 Fishers Lane MSC 9300
Bethesda, MD 20892
(FEDEX/UPS/DHL address: Rockville, MD 20852)
Telephone: (301) 451-2020
FAX: (301) 496-9997
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/publicaccess_Manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The NIH Grants Policy Statement applies to this other transaction unless superseded by Flexible Research Authority (See Section VI.2.A Flexible Research Authority (FRA)). The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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