EXPIRED
Department of Health and Human
Services
Participating Organizations
National
Institutes of Health (NIH), ( http://www.nih.gov)
Components of Participating Organizations
National
Human Genome Research Institute (NHGRI) (http://www.nhgri.nih.gov)
Title: Near-Term Technology Development for Genome
Sequencing (STTR [R41/R42])
Announcement Type
This is a reissue
of RFA-HG-06-019,
which was previously released September 29, 2006
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) SBIR/STTR Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.
Request For Applications (RFA) Number: RFA-HG-07-019
Catalog of Federal Domestic Assistance
Number(s)
93.172
Key Dates
Release/Posted Date: September 11, 2007
Opening Date: October 9, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): October 9, 2007
NOTE: On time submission requires that applications be successfully
submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization).
Application Submission/Receipt Date(s): November 9, 2007
AIDS Application
Submission/Receipt Date(s): Not Applicable
Peer
Review Date(s): January-February 2008
Council
Review Date(s): May 2008
Earliest
Anticipated Start Date(s): July 1, 2008
Additional
Information To Be Available Date (URL Activation Date): September 4, 2007
Expiration
Date: November 10, 2007
Due Dates for E.O. 12372
Not Applicable
Additional Overview
Content
Executive Summary
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 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. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and
Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically
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
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 National Human Genome Research Institute (NHGRI) solicits grant applications under this Funding Opportunity Announcement (FOA) to develop novel technologies that will substantially reduce the cost of genomic DNA sequencing. Current technologies are able to produce the sequence of a mammalian-sized genome of the desired data quality for $5 to $10 million; the goal of this initiative is to reduce costs by at least two orders of magnitude. As some technologies that have potential to achieve this goal are already in or near the commercial market, applications to this FOA will need to show clear advantage over current and emerging technologies.
Parallel FOAs of identical scientific scope (RFA-HG-07-016, RFA-HG-07-017, RFA-HG-07-018) solicit applications under the R01, R21 and Small Business Innovation Research (SBIR) grant programs. Related FOAs (RFA-HG-07-020, RFA-HG-07-021, RFA-HG-07-022, RFA-HG-07-023 ) solicit grant applications to develop technologies to reduce DNA sequencing costs by four orders of magnitude.
Background
The ability to sequence complete genomes and the free dissemination of the sequence data have dramatically changed the nature of biological and biomedical research. Sequence and other genomic data have the potential to lead to remarkable improvement in many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease; advances in agriculture, environmental science and remediation; and the understanding of evolution and ecological systems.
The ability to sequence many genomes completely has been made possible by the enormous reduction of the cost of sequencing in the past two decades, from tens of dollars per base in the 1980s to a fraction of a cent per base today. However, even at current prices, the cost of sequencing a mammalian-sized genome to high quality is about ten million dollars and, accordingly, we have continued to be very selective when choosing new genomes to sequence. The emergence over the past two years of a new generation of sequencing technologies is encouraging. Nevertheless, we remain far away from achieving costs to enable the use of comprehensive genomic sequence information in the study of biology and disease. The rationale for achieving the ability to sequence entire genomes inexpensively is very strong.
There are many areas of high priority research to which genomic sequencing at dramatically reduced cost would make vital contributions:
The broad utility and high importance of dramatically reducing DNA sequencing costs, prompted the NHGRI, in 2004, to embark on two parallel technology development programs. The first, described in this FOA and parallel FOAs for other grant mechanisms, has the objective of reducing the cost of producing a high quality sequence of a mammalian-sized genome by two orders of magnitude to about $100,000. The goal of the second program is the development of technology to sequence a genome for a cost that is reduced by four orders of magnitude to about $1,000. For both programs, the cost targets are defined in terms of a mammalian-sized genome, about 3 gigabases (Gb), with a target sequence quality equivalent to, or better than, that of the mouse assembly published in December 2002 (Nature 420:520, 2002).
The ultimate goal of these programs is to obtain technologies that can produce assembled sequence (i.e., de novo sequencing). However, an accompanying shorter-term goal is to obtain highly accurate sequence data at the single base level, i.e., without assembly information, that can be overlaid on a reference sequence for the same organism (i.e., re-sequencing). This could be achieved, for example, with short reads that have no substantial information linking them to other reads. While the sequence product of this kind of technology would lack some important information, such as information about genomic rearrangements, it would nevertheless potentially be available more rapidly and produce data of great value for certain uses in studying disease etiology and in individualized medicine. Therefore, both programs objectives include a balanced portfolio of projects developing both de novo and re-sequencing technologies. As for de novo sequencing, the goal of technology development for re-sequencing is to reduce costs by two orders of magnitude, and ultimately four orders of magnitude, from the current cost of producing comparable data.
Sequencing strategy and quality
State-of-the-art technology fluorescence detection of dideoxynucleotide-terminated DNA extension reactions resolved by capillary array electrophoresis (CAE) allows the determination of sequence read segments approximately 1000 nucleotides long. If all of the DNA in a 2-3 Gb genome were unique, it would be possible to determine the sequence of the entire genome by generating a sufficient number (10s of millions) of randomly-overlapping 1000-base reads and aligning their overlaps. However, the human and the majority of other interesting genomes contain a substantial amount of repetitive DNA. To cope with the complexities of repetitive DNA elements and to assemble the thousand-base reads in the correct long-range order across the genome, current genomic sequencing methods involve a variety of additional strategies, such as the sequencing of both ends of cloned DNA fragments, use of libraries of cloned fragments of different lengths, incorporation of map information, achievement of substantial redundancy (multiple reads of each nucleotide from overlapping fragments) and application of sophisticated assembly algorithms to filter and align the reads.
The gold standard for genomic sequencing remains 99.99% accuracy (not more than one error per 10,000 nucleotides) with essentially no gaps (http://www.genome.gov/10000923). The final steps in achieving that very high sequence quality cannot be automated and require substantial hand-crafting. However, recent experience suggests that the majority of comparative, and much medically-useful sequence information can be obtained from automatically generated sequence assemblies that have been variously identified as high-quality draft or comparative grade. Therefore, while the ultimate goal is sequencing technology that produces perfect accuracy, the goal of the current de novo sequencing program is to develop technology for automatically generating sequence of at least the quality of the mouse draft genome sequence that was published in December 2002 (Nature 420:520, 2002).
For re-sequencing technologies, in which newly-determined sequence is overlaid on a scaffold of a known reference sequence from other individuals of the same organism, the challenges include the production of sequence of sufficiently high quality to distinguish between sequencing errors and real polymorphism. The presence of gene families with very similar sequence presents another complication, particularly when using technologies that produce short sequence reads. Additional challenges for short-read sequencing include the identification of copy number changes and genomic rearrangements, and the identification of haplotypes (i.e., linear juxtapositioning of particular single nucleotide polymorphism [SNP] alleles along a single chromosome) in diploid organisms. Thus, in proposing the development of re-sequencing technologies, it is essential to state the goals clearly in terms of the technical capability and costs associated with meeting these challenges.
Technology path
Most investigators interested in reducing DNA sequencing costs anticipate that a few additional two-fold decreases in cost can be achieved with the current CAE-based technology, with a realistic lower limit of perhaps $1 million per mammalian-sized genome. However, it is likely that this efficiency will only be achieved in a few very large, well-capitalized, experienced, automated laboratories. To achieve the broadest benefit from DNA sequencing technology for biology and medicine, systems are needed that are not only substantially more efficient but also are easier to use by the average research laboratory.
Efforts are currently under way to streamline the well-established dideoxy terminator chemistry and CAE separation methods, by increasing parallel sample processing while integrating the sample preparation and analysis steps on a single platform. Improvements in separation polymers and fluorescent dyes will facilitate these developments. As these approaches are based largely on the experience of currently successful high-throughput CAE-based methods, they have potential to produce cost savings in the range of several factors of two beyond the current CAE-based systems. They also have the potential to widen the user base for the technology, as the infrastructure and knowledge needed to conduct relatively high-throughput sequencing, or clinical diagnostic sequencing, would be substantially reduced and simplified.
Two methods that were proposed in the early days of the Human Genome Project involve the use of mass spectrometry and sequencing by hybridization. Both methods have been pursued, with some limited success for sequencing, but substantial success for other types of DNA analysis. Both continue to hold additional potential utility for sequencing, although certain inherent limitations will need to be overcome.
More recently, additional methods have been investigated. Two broad approaches are representative.
One is sequencing-by-extension, in which template DNA is elongated in stepwise fashion, and each sequential extension product is detected. Extension is generally achieved by the action of a polymerase that adds a deoxynucleotide, followed by detection of a fluorescent or chemiluminescent signal, and the cycle is then repeated. Variants of this approach rely on other enzymes, such as ligases, and hybridization of labeled oligonucleotides. To obtain sufficient throughput, the method is implemented at a high level of multiplexing, by arraying large numbers of sequencing extension reactions on a surface. Key factors in this general approach include the manner in which the fluorescent signal is generated and the system requirements thus imposed. Depending on the specific approach, challenges of template extension methods include the synthesis of appropriate labeled nucleotide analogues of high purity; identifying processive polymerases that incorporate nucleotide analogs with high fidelity; discriminating the fluorescence of nucleotides that have been incorporated into the growing chain from those present in the reaction mix (background); distinguishing subsequent nucleotide additions from previous ones; accurate enumeration of homopolymer runs (multiple sequential occurrence of the same nucleotide); maintaining synchrony among the multiple copies of DNA being extended to generate a detectable signal or achieving the sensitivity to detect extension of individual DNA molecules; spatial discrimination on the array; and developing fluidics, surface chemistry, and automation to build and run the system. Most current methods using this approach produce short sequence reads (less than 100 bases), so a continuing challenge is to extend read length and develop sequence assembly strategies. Achieving high base calling accuracy continues to be challenging. Remaining challenges notwithstanding, this technology has advanced rapidly, with several commercial platforms either in or nearly in the hands of multiple user groups, and costs moving toward the stated goal of two order-of-magnitude reduction.
Among the numerous candidate technologies for reducing costs by four orders of magnitude is the nanopore sequencing concept, first introduced in the mid-1990s. The goal is to read the linear sequence of nucleotides without copying the DNA and without incorporating labels, relying instead on extraction of signal from the native DNA nucleotides. The requirements include a sensor, perhaps comparable in size to the DNA molecule itself, that interacts sequentially with individual nucleotides in a DNA chain and distinguishes between them on the basis of chemical, physical or electrical properties. Optimal implementation would analyze intact, native genomic DNA isolated from biological, medical or environmental samples without amplification or modification, and would provide very long sequence reads (tens of thousands to millions of bases) rapidly and at sufficiently high redundancy to produce assembled sequence of high quality. Several laboratories have reported significant progress both empirical and toward understanding the theoretical requirements toward achieving these goals. The estimate, stated in 2004, that it may take ten years to conduct the substantial basic research and technology development that are needed to achieve such revolutionary technological advances, appears to be realistic.
While the approaches described immediately above are examples of projects currently being pursued, they are undoubtedly not the only ways to achieve substantially reduced DNA sequencing costs. Also, methods to apply either approach could conceivably lead to that approach being successful for reaching either a two- or four-order of magnitude reduction in the cost of sequencing. NHGRI seeks to support any technology approach that promises to achieve the stated goals. Information on projects previously funded under related FOAs is available at http://www.genome.gov/10000368#6.
Research and Scope
The goal of research supported under this FOA is to develop new or improved technology to enable rapid, efficient genomic DNA sequencing. The specific goal is to reduce sequencing costs by at least two orders of magnitude -- $100,000 serves as a useful target cost for a mammalian-sized genome because the availability of complete genomic sequences at that cost would revolutionize biological research and medicine. While not in a cost range that would enable the use of sequencing in individualized medicine, such technology would permit the sequencing of many genomes for a small fraction of current costs. A 100-fold cost reduction would make possible more extensive studies of human variation for disease gene studies, substantially expanded comparative genomics to understand the human genome, and many other studies relevant to NIH, other federal agencies and the private sector. Entirely new lines of investigation would be enabled by making large-scale sequencing accessible to the diverse interests of many research laboratories and companies.
Investment by NHGRI and others has resulted in substantial progress, such that several groups are now in or near commercial release of instruments and users are gaining experience with the data generated by these systems. The systems, as currently deployed or envisioned within the next year or two, may reach the goal of reducing sequencing costs to about $100,000 per high quality mammalian genome. Yet, there remain substantial challenges to achieving the qualities e.g., read length, read quality, data to support assembly, robust hands-off operation needed to fully achieve the goals of this FOA. Therefore, NHGRI will place highest priority on applications in response to this FOA that either (1) propose to achieve $100,000 genome sequencing by developing new approaches that will outperform those being employed in the current next-generation sequencing technologies, or (2) address specific weaknesses or shortcomings in those methods.
The applicant is expected to articulate specifically advantages relative to the state of the art. An effective way to do so would be to include in the grant application a table that displays achieved and proposed performance of the technology for which support is sought, in comparison with deployed technologies. An example of such a table is shown at the following website: http://www.genome.gov/26022666. The use of such a table is not required, but is offered as a concise format for stating goals in context. Applicants may address advantages of their proposed method by offering additional column headings, and may include any information they might have on the actual performance of other technologies that are on the market or in development.
The scientific and technical challenges inherent in achieving a 100-fold reduction in sequencing costs are considerable. Achieving this goal may require research projects that entail substantial risk. That risk should be balanced by an outstanding scientific and management plan designed to achieve the very high payoff goals of this solicitation. High risk, high payoff projects may fail for legitimate reasons; applicants proposing such projects should describe plans to terminate the project if key milestones cannot be achieved in a reasonable time.
Many projects aimed at next-generation DNA sequencing technologies require substantial advances in a combination of fields such as signal detection, enzymology, chemistry, engineering, bioinformatics, etc. It is therefore anticipated that proposals responding to this FOA will involve fundamental and engineering research conducted by multidisciplinary teams of investigators. The guidance for budget requests accommodates the formation of groups having investigators at several institutions, in cases where that is needed to assemble a team of the appropriate balance, breadth and experience.
Applicants may propose to develop full-scale sequencing systems, or to investigate key components of such systems. For the latter, applicants must describe how the knowledge gained as a result of their project would be incorporated into a full system that they might subsequently propose to develop, or that is being developed by other groups. Such independent proposals are an important path for pursuing novel, high risk/high pay-off ideas.
Research conducted under this FOA may include development of the computational tools associated with the technology, e.g., to extract sequence information, including image analysis and signal processing, and to evaluate sequence quality and assign confidence scores. It may also address strategies to assemble the sequence from the information being obtained from the technology or by merging the sequence data with information from parallel technology. However, this FOA will not support development of sequence assembly or sequence analysis software independent of technology development to obtain the sequence.
The quality of sequence to be generated by the technology is of paramount importance for this solicitation. Two major factors contributing to genomic sequence quality are per-base accuracy and contiguity of the assembly. Much of the utility of comparative sequence information will derive from characterization of sequence variation between species, and between individuals of a species. Therefore, per-base accuracy must be high enough to discern polymorphism at the single-nucleotide level (substitutions, insertions, deletions). Experience and resulting policy have established a target accuracy of not more than one error per 10,000 bases. All applications in response to this FOA, whether to develop re-sequencing or de novo sequencing technologies, must propose achieving per-base quality at least to this standard.
Assembly information is needed for determining sequence of new genomes, and ultimately also for genomes for which a reference sequence exists, to detect rearrangements, insertions, deletions, and copy number changes. All of these are associated with disease, and knowledge of rearrangements can reveal new biological mechanisms. The phase of single nucleotide polymorphisms to define haplotypes is important in understanding and diagnosing disease. Achieving a high level of sequence contiguity may be essential to achieve the full benefit from the use of sequencing for individualized medicine, e.g., to evaluate genomic contributions to risk for specific diseases and syndromes, and drug responsiveness. Nevertheless, it is recognized that perfect sequence assembly from end to end of each chromosome is unlikely to be achievable with most technologies in a fully automated fashion and without adding considerable cost. Therefore, for the purpose of this solicitation, grant applications proposing technology development for de novo sequencing shall describe how they will achieve, for about $100,000, a draft-quality assembly that is at least comparable to that represented by the mouse draft sequence produced by December 2002: 7.7-fold coverage, 6.5-fold coverage in Q20 bases, assembled into 225,000 sequence contigs connected by at least two read-pair links into supercontigs [total of 7,418 supercontigs at least 2 kb long], with N50 length for contigs equal to 24.8 kb and for supercontigs equal to 16.9 Mb (Nature 420:520, 2002). Grant applications that propose technology development for re-sequencing should explain how they will achieve a two-order-of magnitude reduction in cost compared to technologies that can produce similar quality of data, today.
The grant applications will be evaluated, and funding decisions made, in such a way as to develop a balanced portfolio that has strong potential to develop both robust re-sequencing and de novo sequencing technologies. If the estimate is correct, that achieving the goal of a 100-fold cost reduction for de novo genome sequencing will be achieved by about 2009, then low-cost re-sequencing technologies might be expected to be demonstrated in a shorter time. Grant applications that present a plan to achieve high quality re-sequencing while on the path to high quality de novo sequencing will receive high priority. Similarly, applications that propose to reduce costs by two orders of magnitude while on a path to four orders of magnitude will also receive high priority.
The major focus of this FOA funding opportunity announcement is on the development of new technologies for detection of nucleotide sequence. Any new technology will eventually have to be incorporated effectively into the entire sequencing workflow, starting with a biological sample and ending with sequence data of the desired quality, and this issue should be addressed. Sample preparation requirements are a function of the detection method and the sample detection method affects the way in which output data are handled. Therefore, these aspects of the problem are clearly relevant and should be addressed in an appropriate timeframe in the research plan. However, applicants should address the most critical and highest-risk aspects of the project, on which the rest of the project is dependent, as early as possible in the research plan.
Practical implementation issues related to workflow and process control for efficient, high quality, high-throughput DNA sequencing should be considered early in system design. Some technology development groups lack practical experience in high throughput sequencing, and in testing of methods and instruments for robust, routine operation. Applicants may therefore wish to include such expertise as they develop their suite of collaborations and capabilities.
The goal of this research is to develop technology to produce sequence from entire genomes. Projects have been launched to determine sequence from selected important regions (e.g., all of the genes). Grant applications that propose to meet the cost targets by sequencing only selected regions of a genome will be considered unresponsive to this RFA. However, applications that propose novel ways to sequence selected genomic regions, cost-effectively, while on a path to whole-genome sequencing, are responsive.
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 Small Business Technology Transfer (STTR [R41/R42] grant
mechanisms. Applications may be submitted
for support as Phase I, Phase II, or Fast-Track grants as described in the
SF424 (R&R) SBIR/STTR Application Guide.
Small
business concerns that have received a Phase I STTR grant may apply for Phase
II funding of that project. The Phase II must be a logical extension of the
Phase I research but not necessarily as a Phase I project supported in response
to this funding opportunity. Phase II applications will compete with all STTR
applications and will be reviewed according to the customary peer review
procedures
The applicant small business concern (SBC) will be solely responsible for
planning, directing, and executing the proposed project.
This
funding opportunity uses Just-in-Time information concepts. The modular
budget format is not accepted for STTR grant applications. Applicants must
complete and submit budget requests using the SF424 Research and Related
(R&R) Budget component found in the application package attached to this
FOA in Grants.gov/Apply.
2. Funds Available
The SF424 (R&R) SBIR/STTR Application
Guide indicates the statutory guidelines of funding
support and project duration periods for Phase I and Phase II STTR awards. For
this funding opportunity, budgets up to $250,000 total
costs per year and time periods up to two years for Phase I may be requested. Budgets up to $1.5 million total
costs per year and up to three years may be requested for
Phase II. Total costs include direct costs, Facilities & Administrative
(F&A)/indirect costs, and fee.
The participating
organization, NHGRI, intends to commit approximately $1.8 million dollars in FY 2008 to fund 2-4 Phase I, Phase II, or Fast Track applications under the
STTR set-aside funding mechanism. Although the financial plans of the
participating organizations provide support for this program, awards pursuant
to this FOA are contingent upon the availability of funds and the submission of
a sufficient number of meritorious applications.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
Only United States small business concerns (SBCs) are eligible to submit STTR applications. A small
business concern is one that, at the time of award for both Phase I and Phase
II STTR awards, meets all of the following criteria:
1. Organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;
2. In the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there can be no more than 49 percent participation by business entities in the joint venture;
3. At least 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States.
4. Has, including its affiliates, not more than 500 employees and meets the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both.
Control can be exercised through common ownership, common management, and contractual relationships. The term "affiliates" is defined in greater detail in 13 CFR 121.3-2(a). The term "number of employees" is defined in 13 CFR 121.3-2(t).
Business concerns include, but are not limited to, any individual (sole proprietorship), partnership, corporation, joint venture, association, or cooperative. Further information may be obtained by contacting the Small Business Administration Size District Office at http://sba.gov/size.
One of the circumstances that would lead to a finding that an organization is controlling or has the power to control another organization involves sharing common office space and/or employees and/or other facilities (e.g., laboratory space). Access to special facilities or equipment in another organization is permitted (as in cases where the awardee organization has entered into a subcontractual agreement with another organization for a specific, limited portion of the research project). However, research space occupied by an STTR awardee organization must be space that is available to and under the control of the STTR awardee for the conduct of its portion of the proposed project.
Title 13 CFR 121.3 also states that control or the power to control exists when key employees of one concern organize a new concern ... and serve as its officers, directors, principal stockholders, and/or key employees, and one concern is furnishing or will furnish the other concern with subcontracts, financial or technical assistance, and/or other facilities, whether for a fee or otherwise. Where there is indication of sharing of common employees, a determination will be made on a case-by-case basis of whether such sharing constitutes control or the power to control.
For purposes of the STTR program, personnel obtained through a Professional Employer Organization or other similar personnel leasing company may be considered employees of the awardee. This is consistent with SBA’s size regulations, 13 CFR 121.106 Small Business Size Regulations.
All STTR grant applications will be examined with the above eligibility considerations in mind. If it appears that an applicant organization does not meet the eligibility requirements, NIH will request a size determination by the SBA. If eligibility is unclear, NIH will not make an STTR award until the SBA provides a determination.
Note: An applicant organization that has been determined previously by SBA to be other than small for a size standard of not more than 500 employees or for purposes of the SBIR/STTR program, the organization must be recertified by the SBA prior to any future SBIR/STTR awards.
1.B. Eligible Individuals
Any
individual with the skills, knowledge, and resources necessary to carry out the
proposed research is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application
for projects that require a team science approach that clearly does not fit
the single-PD/PI model. Additional information on the implementation plans and
policies and procedures to formally allow more than one PD/PI on individual
research projects is available at http://grants.nih.gov/grants/multi_pi . All PDs/PIs must be registered in the NIH eRA Commons prior to the submission
of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).
The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
For a STTR application, the Project Director/Principal Investigators (PD/PIs) may be employed with the SBC or the participating non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual.
When the proposed PD/PI clearly does not have sufficient qualifications to assume this role, the application is not likely to receive a favorable evaluation.
Each PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration. In all cases, however, the PD/PI s official relationship with the grantee must entail sufficient opportunity for the PD/PI to carry out his or her responsibilities for the overall scientific and technical direction of the project. Documentation (e.g., consultant, consortium and contractual arrangements) describing the official relationship of the PD/PI with the applicant small business concern should NOT be submitted with the grant application, but a copy must be furnished upon the request of the NIH awarding component.
The following are examples of situations describing the official relationship of the PD/PI with the applicant small business organization:
2. Cost Sharing or Matching
This program does not
require cost sharing as defined in the current NIH
Grants Policy Statement.
3. Other-Special Eligibility Criteria
In
STTR Phase I and Phase II, at least 40% of the work must be performed by the
small business concern and at least 30% of the work must be performed by the
single, partnering research institution. The basis for determining the
percentage of work to be performed by each of the cooperative parties will be
the total of direct and F&A/indirect costs attributable to each party,
unless otherwise described and justified in Item 12, Consortium/Contractual
Arrangements, of the PHS398 Research Plan component of the SF424 (R&R)
application forms.
Applicants may not simultaneously submit identical/essentially identical applications under both this STTR funding opportunity and any other HHS FOA, including the current SBIR and STTR Parent FOAs. The NIH will accept as many "different" applications as the applicant organization chooses. However, the NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process or service that, with non-substantive modifications, can be applied to a variety of purposes. Likewise, identical or essentially identical grant applications submitted by different organizations will not be accepted. Applicant organizations should ascertain and assure that the materials they are submitting on behalf of the principal investigator are the original work of the principal investigator and have not been used elsewhere in the preparation and submission of a similar grant application. Applications to the NIH are grouped by scientific discipline for review by individual Scientific Review Groups and not by disease or disease state. The reviewers can thus easily identify multiple grant applications for essentially the same project. In these cases, application processing may be delayed or the application(s) may be returned to the applicant without review.
It is unlawful to enter into contracts or grants requiring essentially equivalent work or effort. Essentially equivalent work or effort occurs when (1) substantially the same research is proposed for funding in more than one contract proposal or grant application submitted to the same Federal agency; (2) substantially the same research is submitted to two or more different Federal agencies for review and funding consideration; or (3) a specific research objective and the research design for accomplishing an objective are the same or closely related in two or more proposals or awards, regardless of the funding source. If there is any question concerning essentially equivalent work or effort, it must be disclosed to the soliciting agency or agencies before award.
Only one Phase II award may be made for a single SBIR/STTR project.
You may submit a Phase II application either before or after expiration of the Phase I budget period, unless you elect to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II support, a Phase I grantee organization should submit a Phase II application within the first six receipt dates following the expiration of the Phase I budget period.
Applications for renewal or
supplementation of existing projects are eligible to compete with applications
for new awards. Applicants for phase II awards must have received Phase I
funding for an appropriately related project, but that funding need not have
been awarded in response to a specific RFA.
Section IV. Application and Submission Information
To download a SF424 (R&R)
Application Package and SF424 (R&R) SBIR/STTR Application Guide for
completing the SF424 (R&R) forms for this FOA, use the Apply for Grant
Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.
Several additional separate actions are required before an applicant SBC can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Started
2) Organizational/Institutional Registration in the eRA Commons
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
To affiliate the PD/PI with the applicant small business concern:
1. PD/PI gives Commons user ID and email address to the administrator of the applicant organization/institution. (The email address must be the one that is contained in the Personal Profile for the PD/PI.)
2. Administrator logs into the Commons. (The administrator can be the Signing Official, Administrative Official, or the Accounts Administrator.)
3. Administrator selects "Administration" tab and then "Accounts" tab.
4. Administrator selects "Create Affiliation" tab.
5. Administrator enters the Commons User ID and Email address into the appropriate fields and clicks "Submit."
Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.
1. Request Application Information
Applicants must download
the SF424 (R&R) application forms and SF424 (R&R) SBIR/STTR Application
Guide for this FOA using the Apply for Grant Electronically button in this
FOA or through Grants.gov/Apply.
Note: Only the forms package directly attached to a specific
FOA can be used. You will not be able to use any other SF424 (R&R) forms
(e.g., sample forms, forms from another FOA), although some of the
"Attachment" files may be useable for more than one FOA.
For further assistance contact GrantsInfo: Telephone
301-710-0267, Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY
301-451-5936.
2. Content and Form of Application Submission
Prepare all STTR applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) SBIR/STTR Application Guide.
The SF424 (R&R) SBIR/STTR Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Failure to include this data field will cause the application to be rejected.
Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/ APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:
Required
Components:
SF424
(R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research
& Related Other Project Information
Research
& Related Senior/Key Person
Research
& Related Budget
Research
& Related Subaward Budget Attachment(s) Form
PHS398
Cover Page Supplement
PHS398
Research Plan
PHS398
Checklist
SBIR/STTR
Information
Optional
Components:
PHS398
Cover Letter File
SPECIAL INSTRUCTIONS
Applications with Multiple PDs/PIs
When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above. All funding for STTR projects goes to the small business awardee, so funding for PD/PIs from other organizations must be requested via a subcontract with the small business using the Research & Related Subaward Budget Attachment(s) Form.
Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.
All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.
If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.
3. Submission Dates and Times
See Section IV.3.A. for details.
3.A.
Submission, Review, and Anticipated Start Dates
Opening Date: October 9, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s):October 9, 2007
Application Submission/Receipt
Date(s): November 9, 2007
Peer Review
Date(s): January-February 2008
Council Review Date(s): May 2008
Earliest Anticipated Start
Date(s): July
1, 2008
3.A.1.
Letter of Intent
Prospective applicants
are asked to submit a letter of intent that includes the following information:
Although
a letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows Institute
and Center (IC) staff to estimate the potential review workload and plan the
review.
The letter of intent is
to be sent by the date listed in Section IV.3.A.
The letter of intent
should be sent to:
Jeffery A. Schloss, Ph.D.
Division of Extramural Research
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9305
Telephone: (301) 496-7531
Email: schlossj@exchange.nih.gov
3.B. Submitting an
Application Electronically to the NIH
To submit an application in response to this FOA, applicants may use the Apply for Grant Electronically button in this FOA
or link to http://www.grants.gov/applicants/apply_for_grants.jsp
and follow steps 1-4. Note: Applications must only be submitted
electronically. PAPER APPLICATIONS WILL
NOT BE ACCEPTED.
In order
to expedite the review, applicants are requested to notify the NHGRI Referral Office by email (kn24c@nih.gov) when the application has been
submitted. Please include the FOA number and title, and PD/PI name
and title of the application.
3.C.
Application Processing
Applications may be submitted on or after the opening date and must be successfully
received by Grants.gov no later than 5:00 p.m. local time (of the
applicant institution/organization) on the application submission/receipt
date(s). (See Section IV.3.A. for all dates.) If an
application is not submitted by the receipt date(s) and time, the application
may be delayed in the review process or not reviewed.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image to determine if any further action is necessary.
Upon receipt,
applications will be evaluated for completeness by the Center for Scientific
Review (CSR) and responsiveness by the NHGRI.
Incomplete and non-responsive applications will not be reviewed.
There will be
an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives
the Grants.gov acknowledgments. The AOR and the PD/PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific
Review Group is also in the Commons.
Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.
The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).
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.
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 renewal 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 renewal 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 the NIH
Grants Policy Statement.
6. Other Submission
Requirements
Supplementary Instructions
Projects that propose to build sequencing systems (in contrast to developing components) that will be assembled by the end of the project period may wish to present a strong case for that system’s capabilities by proposing to demonstrate the sequencing of a substantial amount of DNA (e.g., mega- to gigabases) at the target cost and quality; other measures may be proposed by the applicant.
A detailed research plan must be presented. The application should include a description of the level of risk of key technical challenges, alternative approaches, go/no-go decision points, etc. It should also include a detailed timeline accompanied by quantitative milestones (see below) that address the key scientific and technical challenges central to the approach. The timeline and milestones are essential for use by the grantee and the NHGRI for planning the research project and assessment of progress toward goals, and by the reviewers for evaluating the proposal.
Timelines and quantitative milestones are essential for development of a realistic research plan; they provide a basis for project leaders to make decisions, assess their own progress, set priorities, and redistribute resources when needed. It will be particularly important to establish quantitative milestones in cases where subsequent steps in technology development depend upon threshold performance characteristics of earlier developments. Elaboration of timelines and milestones is primarily the responsibility of the applicant, and the quality and utility of the proposed timelines and milestones will be a review criterion, because they reflect the insights and judgment of the applicant concerning key challenges and how best to conduct the research. The NHGRI appreciates that these projects will require research, not just engineering; progress toward milestones will be evaluated accordingly. If the proposed timeline and milestones are not adequate in the case of an otherwise meritorious proposal, reviewers of the application may make recommendations to NHGRI regarding improved timelines and milestones.
To accelerate progress in the field of advanced DNA sequencing technology development, grantees will be required to participate actively and openly in at least one grantee meeting per year. Substantial information sharing will be required and is a condition of the award; failure to openly share information will be grounds for discontinuation of funding. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops; their agreement to share information substantially will be a prerequisite to participation. Applicants should request travel funds in their budgets for the Principal Investigator and two additional lead investigators to attend the annual meetings.
Applicants may include funds for an internally appointed advisory board. However, they should not contact potential advisors, nor should potential advisors be named in the grant application, to avoid conflicts of interest in the review process.
All applicants must describe their plan for providing access to the technology developed under this grant support, and information about that technology. For example, the technology might be made available as a fee-for-service, through sale of instruments and/or reagents, through collaboration, through publication and posting of results, plans and methods, or by other means. If any quantity of sequence data will be collected under grant support, a plan to disseminate those data must be described.
In summary, applicants must incorporate into application section 5 (Research Design and Methods):
In addition to sections 2-5 of the PHS 398 research plan, applicants must include a management plan (not to exceed 4 pages) incorporating:
Page limits for the management plan are in addition to the page limits for the research plan. The management plan should be included under Other Research Plan Sections, 17. Resource Sharing Plan, of the 424 R&R form.
PD/PI Credential (e.g., Agency Login)
The NIH requires each PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.
Organizational DUNS
The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
PHS398 Research Plan Component Sections
While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
All application instructions outlined in the SF424 (R&R) SBIR/STTR Application Guide are to be followed, with the following requirements.
STTR Phase I applications:
STTR Phase II applications:
STTR Fast-Track applications:
Warning: Please be sure that you observe the total cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.
Appendix Materials
NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.
Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).
Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process. Phase I SBIR/STTR Appendix materials are not permitted unless specifically requested by NIH.
Plan
for Sharing Research Data
All applicants must include a plan for sharing data or
explain why data sharing is not possible. 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 are required to describe
their plan to share data at grantee meetings, and are required to describe
plans to disseminate the technology and information about the technology that
is being developed under this grant support. These requirements are described
in the section immediately above (Other Submission Requirement, Supplementary
Instructions). If the final data are not
amenable to sharing, for example, if they are proprietary, this must be
explained in the application. The Small Business Act requires NIH to protect
from disclosure and nongovernmental use all SBIR and STTR data developed from
work performed under an SBIR and STTR funding agreement for a period of four
(4) years after the closeout of either a Phase I or Phase II grant unless NIH
obtains permission from the awardee to disclose these data. The data rights
protection period lapses only upon expiration of the protection period
applicable to the SBIR and STTR award, or by agreement between the small
business concern and NIH. If new sequence data (rather than sequencing
to validate technology using known sequence templates) will be collected during
the project, then the applicant should describe data release plans consistent
with NHGRI’s strongly-endorsed rapid release of genomic data and
materials. The specific NHGRI policy on release of sequence data is
available at http://www.genome.gov/10506376.
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.
Sharing Research
Resources
NIH policy expects that grant 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/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), See Section VI.3.,
Reporting.
Section V. Application Review Information
1.
Criteria
Only the review
criteria described below will be considered in the review process.
2. Review and
Selection Process
Applications
that are complete and responsive to this funding opportunity will be evaluated
for scientific and technical merit by an appropriate peer review group convened
by NHGRI in accordance with the review
criteria stated below.
As part of the
initial merit review, all applications will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended STTR applications. The following will be considered in making funding decisions:
The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's 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.
Applicants
should include information in relevant sections of the grant application that addresses
the questions for each review criterion below.
All STTR Applications
Significance: Does the proposed project have
commercial potential to lead to a marketable product, process or service? Does
this study address an important problem? What may be the anticipated commercial
and societal benefits that may be derived from the proposed research? 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 the application lead to enabling technologies (e.g.,
instrumentation, software) for further discoveries? Will the technology have a
competitive advantage over existing/alternate technologies that can meet the
market needs?
Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Is the proposed plan a sound approach for establishing technical and commercial feasibility? Are the milestones and evaluation procedures appropriate? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PD/PIs, is the leadership approach, including he designated roles and responsibilities governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PD/PIs?
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?
Investigator(s): Are the PD/PI(s) and other key
personnel appropriately trained and well suited to carry out this work? Is the
work proposed appropriate to the experience level of the PD/PI(s) and other
researchers, including consultants and subcontractors (if any)? Do the PD/PIs
and investigative team bring complementary and integrated expertise to the
project (if applicable)? Are the relationships of the key personnel to the
small business and to other institutions appropriate for the work proposed?
Environment: Do(es) the scientific and technological 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 sufficient access to resources (e.g., equipment, facilities)?
Phase II
Applications
In
addition to the above review criteria:
1. How well did the
applicant demonstrate progress toward meeting the Phase I objectives,
demonstrating feasibility, and providing a solid foundation for the proposed
Phase II activity?
2. Did the applicant
submit a concise Commercialization Plan that adequately addresses the specific
areas described in the SF424 (R&R) SBIR/STTR Application Guide and the
SBIR/STTR Information component?
3. Does the project
carry a high degree of commercial potential, as described in the
Commercialization Plan?
Phase I/Phase II
Fast-Track Application Review Criteria
For Phase
I/Phase II Fast Track applications, the following criteria also will be
applied:
1. Does the Phase I
application specify clear, appropriate, measurable goals (milestones) that
should be achieved prior to initiating Phase II?
2. Did the applicant submit
a concise Commercialization Plan that adequately addresses the specific areas
described in the SF424 (R&R) SBIR/STTR Application Guide and the SBIR/STTR
Information component?
3. To
what extent was the applicant able to obtain letters of interest, additional
funding commitments, and/or resources from the private sector or non-SBIR/STTR
funding sources that would enhance the likelihood for commercialization?
4. Does the project
carry a high degree of commercial potential, as described in the Commercialization
Plan?
Phase I and Phase II
Fast-Track applications that satisfy all of the review criteria will receive a
single rating.
For Fast-Track
applications, the Phase II portion may not be funded until a Phase I final
report and other documents necessary for continuation have been received and
assessed by program staff that the Phase I milestones have been successfully
achieved. Items 2-5 of the Research Plan may not exceed 25 pages. That is, the
combined Phase I and Phase II plans for a Fast-Track application (for Items
2-5) must be contained within the 25-page limitation.
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:
Resubmission
Applications (formerly revised/amended applications): Are the responses to comments from
the previous scientific review group adequate? Are the improvements in the
resubmission application appropriate?
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 item 6 of the Research Plan
component of the SF424 (R&R).
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 item
7 of the Research Plan component of the SF424 (R&R).
Care and Use of Vertebrate Animals in
Research: If vertebrate animals are to
be used in the project, the five items described under item 11 of the Research
Plan component of the SF424 (R&R) 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 and Period of Support: The reasonableness of the proposed
budget and the appropriateness of the requested period of support in relation
to the proposed research may be assessed by the reviewers. 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. The data sharing plan includes the plan for sharing
data at grantee meetings, plans for data and technology dissemination, and
plans for rapidly depositing sequence data into public databases (if
applicable).
2.D. Sharing Research
Resources
NIH policy expects that grant 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_2003/NIHGPS_Part7.htm#_Toc54600131). 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.
Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations.
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/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.
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.
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
Prior to funding an application, the NHGRI
will negotiate the milestones with the applicant, beginning with the
applicant ’s stated milestones and incorporating recommendations from the review
panel, the National Advisory Council for Human Genome Research, and staff. The
negotiated milestones will become a condition of the award, including
appropriate language to recognize that the project includes research whose
outcomes are unpredictable. In the case of research programs projected to
require longer than the initial grant period, the decision to fund beyond the
initial period will be based on a competitive renewal process that will take
into account overall progress in the field as well as progress on the individual
research effort, as compared to the negotiated milestones.
To accelerate progress in the field of advanced DNA sequencing technology
development, grantees will be expected to participate actively and openly in at
least one grantee meeting per year. Substantial information sharing will be
required and is a condition of the award; failure to openly share information
will be grounds for discontinuation of funding. It is understood that some
information developed under the grants will be proprietary and cannot be shared
immediately without damaging the commercialization potential of the technology.
Applicants should describe their plans for participating in the grantee
meetings and for managing the intellectual property concerns in the context of
those meetings and other opportunities for information sharing. Other
investigators in the field (i.e., not supported under this program) may be
invited to participate in these workshops; their agreement to share information
substantially will be a prerequisite to their participation. The applicant s
participation plan, after negotiation with NHGRI staff, will become the minimum
standard for continued funding.
Grantees may be asked to host the annual grantee meetings on a rotating basis.
The NHGRI will negotiate a schedule for the grantee meetings and will adjust
budgets to accommodate these meetings. Holding these meetings at grantee sites
or in association with other meetings will facilitate information sharing and
participation of a larger portion of the research staff than would otherwise
occur.
The applicant’s plans, as negotiated with staff, for complying with timelines
and milestones, participation in grantee meetings, submitting progress reports,
and sharing research data will be conditions of the award.
All NIH grant and cooperative agreement awards include
the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and
Conditions of NIH Grant Awards, Subpart A: General and Part
II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions
for Specific Types of Grants, Grantees, and Activities.
3. Reporting
NIH requires that
SBIR/STTR grantees submit the following
reports within 90 days of the end of the grant budget period unless
the grantee is under an extension.
Financial Status Report (OMB 269, http://www.whitehouse.gov/omb/grants/grants_forms.html)
Final Progress Report
Final Invention Statement and Certification (HHS 568)
Annual Invention Utilization Reports
Final Cash Transaction Report (PSC 272, http://www.dpm.psc.gov/Reports.aspx)
Phase II Data Collection Requirement for Government Tech-Net Database (http://technet.sba.gov)
Failure to submit timely final reports may affect future funding to the organization or awards with the same principal investigator.
For details about each specific required report, see the section on Award Guidelines, Reporting Requirements, and Other Considerations, in the SF 424 (R&R) SBIR/STTR Application Guide.Applicants must plan to submit two progress reports per year
one at the time of the non-competing continuation and one at a time to be
determined by NHGRI staff. The latter may coincide with grantee meetings,
meetings of advisors to NHGRI, or site visits. The NHGRI will use information
from reports, meetings, site visits, etc. to evaluate each grantee progress
and the success of the overall program; this information will be used to determine
if funding levels should be increased or decreased for future years, for each
grant, and for the program.
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:
Jeffery
A. Schloss, Ph.D.
Division of Extramural Research
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9305
Telephone: (301) 496-7531
Email: schlossj@exchange.nih.gov
2. Peer Review Contacts:
Ken
Nakamura, Ph.D.
Scientific Review Branch
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9306 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone: (301) 402-0838
E-mail: kn24c@nih.gov
3. Financial or Grants Management Contacts:
Cheryl
Chick
Grants Administration Branch
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9306
Phone: (301) 435-7858
Fax: (301) 402-1951
E-mail: chickc@mail.nih.gov
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 (45 CFR 46) 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 scientific merit or the priority score.
Access to Research Data through the Freedom of Information
Act:
The 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 the 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). Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal 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 SF424 (R&R); 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://publicaccess.nih.gov/ and view
the Policy or other Resources and Tools including the Authors' Manual.
Standards for Privacy of Individually Identifiable
Health Information:
The Department of Health and Human Services (HHS)
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 HHS 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. For publications listed in the appendix and/or
Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission
identification numbers must be used for publicly accessible on-line journal
articles. Publicly accessible on-line journal articles or PMC
articles/manuscripts accepted for publication that are directly relevant to the
project may be included only as URLs or PMC submission
identification numbers accompanying the full reference in either the
Bibliography & References Cited section, the Progress Report Publication
List section, or the Biographical Sketch section of the NIH grant application.
A URL or PMC submission identification number citation may be repeated in each
of these sections as appropriate. There is no limit to the number of URLs or
PMC submission identification numbers that can be cited.
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 FOA 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 Part 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
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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NIH Funding Opportunities and Notices
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