Part I Overview Information

Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov)

Title: Genomic, Proteomic, and Metabolomic Fingerprints as Alcohol Biomarkers (SBIR/STTR)

Announcement Type
New

NOTICE: This funding opportunity must be read in conjunction with the current Omnibus Solicitation of the National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration for Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grant Applications. The solicitation (see http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf (PDF) or http://grants.nih.gov/grants/funding/sbirsttr1/index.doc (MS Word)) contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. All of the instructions within the current SBIR/STTR Omnibus Solicitation apply. Exceptions are noted in the Executive Summary.

Request For Applications (RFA) Number: RFA-AA-06-001

Catalog of Federal Domestic Assistance Number(s)
93.273

Key Dates
Release Date: March 23, 2005
Letters Of Intent Receipt Date(s): June 17, 2005
Application Receipt Dates(s): July 15, 2005
Peer Review Date(s): October/November, 2005
Council Review Date(s): January, 2006
Earliest Anticipated Start Date: March 1, 2006
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: July 16, 2005

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

This funding opportunity will utilize the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) mechanisms, but will be run in parallel with an RFA of identical scientific scope (RFA-AA-06-002) that will utilize the traditional research project grant (R01) or the exploratory/developmental (R21) grant mechanism.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

  Section I. Funding Opportunity Description
    1. Research Objectives

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

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

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

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

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

Acute, chronic or excessive ingestion of alcohol often leads to a variety of medical disorders which have a significant impact on our society. These medical disorders include alcohol liver disease, pancreatitis, cardiovascular disease, fetal abnormalities, brain damage, and other alcohol-induced organ damage. There is a well-recognized but unmet need for prognostic and diagnostic biomarkers and the biomarkers that can monitor the response of treating these alcohol-induced organ damage in clinical practice. Although several alcohol biomarkers have been used in clinics for years, their accuracy, sensitivity, or specificity needs to be improved. Currently no clinically available laboratory test can reliably diagnose excessive alcohol use or predict the progression of alcohol-induced organ damage. According to an expert working group convened by National Institutes of Health, a biomarker is defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention” (Clin Pharmacol Ther. 69, 89-95, 2001). Biomarkers of alcohol exposure and alcohol-induced organ damage have several fundamental purposes in alcohol research and clinical practice. First, they can be indicators of problematic drinking and alcohol-related organ damage. Biomarkers that can detect organ damage at early stage can provide not only valuable information for patients to seek early medical intervention but also a tool of screening in a large population. Second, they can monitor or predict the progression of organ damage. Third, they can monitor and evaluate patients in alcoholism treatment and prevention programs. Fourth, biochemical tests of alcohol intake could provide motivational feedback during treatment. Fifth, they can provide objective measurement during pharmacological and behavioral clinical trials. Finally, they can disclose recent drinking in social and problematic drinkers in high-risk situations, such as during pregnancy. The discovery of novel biomarkers to prognose, diagnose, and monitor the alcohol exposure and alcohol-induced organ damage for their disease type, status, progression, and response to treatment is of great importance for both alcohol research and clinical practice.

The traditional approach of biomarker discovery, which usually focuses on one or a few potential candidates at a time, has been ineffective and led to a low rate of biomarker discovery with clinical utility. Alcohol-induced physiological changes are affected by a variety of biological and environmental factors. The effects of alcohol are the consequences of molecular alterations at the DNA, RNA, protein, and metabolite levels. The complete sequencing of the human, mouse, and rat genomes and recent advances in genomic, proteomic, and metabolomic technologies offer tremendous opportunities for biomarker discovery. These high-throughput technologies are emerging as powerful platforms for more global approaches to discover pattern-based unique molecular fingerprints or signatures that are associated with alcohol-induced organ damage.

At the DNA level (genome), various global genomic technologies can be applied to study genetic variation, gene mutation, gene mapping, and epigenetic regulation. At the RNA level (transcriptome), DNA microarray and other global genomic technologies can be used to study quantity of RNA and their alternative splicing. At the protein level (proteome), proteomic technologies can systematically study the identity, quantity, modification, localization, and function of all the proteins in a cell, often in a high-throughput manner. The proteomic approaches would extend the power of the global genomic analyses for the following four primary reasons. (1) RNA expression often does not correlate with protein expression, which is a more critical indicator of the gene activity. (2) The activity of a protein could be significantly modulated by post-translational modification, which cannot be reflected at the RNA level. (3) The function of a gene is executed by its protein product in a specific sub-cellular compartment. (4) Proteins are normally more stable than RNA in both cells and body fluids. In addition, a protein molecule provides many more targets for regulation (quantity, functional activity, structure, post-translational modification, localization, etc.), while RNA can be mostly targeted for its quantity. The stability and multiple layers of regulation of proteins make them much better candidates as biomarkers or targets for therapeutic interventions.

At the metabolite level (metabolome), metabolomics involves a detailed, quantitative analysis of low molecular weight metabolites over changing environmental conditions (e.g., alcohol administration) in a biological system (human patients or animal models). Metabolites are the intermediate and end products of cellular function, and their levels and modulation are definitive reflections of an organism's response to genetic or environmental perturbations. The determination of these metabolites can be achieved by using a variety of tools such as mass spectrometry, nuclear magnetic resonance (NMR), capillary electrophoresis and HPLC/FPLC, in conjunction with a wide range of bioinformatic, statistical, and computational tools. A virtual snapshot image can be obtained of the myriad of small molecules within the organism and how these molecules are modulated in individual time frames. The advantage of metabolomic studies in alcohol research is that it can extract latent biochemical information of diagnostic or prognostic value, reflecting actual biological events and can serve as a sentinel for diseases. It also offers approachable solutions since in general there are far fewer metabolites than genes or gene products.

To make sense of large and complex datasets generated through these high-throughput technologies, bioinformatic tools are essential for data management, analysis, and biomarker-directed data mining activities during the biomarker discovery process. They are also essential for the integration of the data in genomic, proteomic, and metabolomic analyses, as well as the integration with other experimental and clinical measurements.

The unique molecular fingerprints identified through genomic, proteomic, and metabolomic studies reflect both the genetic make-up and the cumulative responses to alcohol exposure and environmental perturbations. The information obtained can be integrated to define biomarkers based on entire groupings of alterations in unison that are associated with alcohol exposure and alcohol-induced organ damage. The information obtained through genomic, proteomic, and metabolic studies can also be integrated with other experimental and clinical measurements to identify complex systems-level responses to alcohol and environmental perturbations. These new biomarkers could not only broaden insights into the cause of the diseases, but also provide new prognostic, diagnostic, and therapeutic avenues.

Research Objectives

This RFA solicits applications in the fields of genomics, proteomics, and metabolomics to identify novel biomarkers associated with alcohol exposure or alcohol-induced organ damage for their prognosis, diagnosis, screening, monitoring of treatments, and surveillance of recurrence. It can be anticipated that these global approaches, complemented with other traditional approaches, hold great promise for discovering many unique molecular fingerprints as sensitive and accurate biomarkers for alcohol exposure and alcohol-induced organ damage.

To achieve these objectives, several desirable features of biomarkers are necessary. At a fundamental level, the biomarkers must be accurate. For example, when used to measure alcohol exposure over time, they can distinguish harmful, problematic drinking from light to moderate, non-problematic drinking or abstinence. When used in diagnosis of organ damage or their progression, the probability of their accuracy has to be also reasonably high. In addition, the assay should be reliable, yielding reproducible results. The biomarkers have to be also sensitive, using only reasonable amount of samples. Furthermore, the samples or tissues used for biomarker detection should be easily obtainable. Sample collection and the assay must be relatively simple and accepted by the practitioner and patient. Examples of these types of samples include, but not limited to, blood, urine, saliva, hair, etc. Finally, a biomarker detection assay should be incorporated easily into diverse settings, including alcoholism treatment centers, primary care offices, specialized medical settings, or the work place .

Areas of investigation under this RFA could include, but are not limited to:

This RFA strongly encourages the collaboration between alcohol researchers and non-alcohol researchers with expertise in the fields of genomics, proteomics, metabolomics, and bioinformatics.

The applications that propose only to catalog the expression of RNA, protein, or metabolite as their final goal are not considered to be responsive to this RFA. In addition, the applications proposing further characterization of the known alcohol biomarkers will be considered non-responsive as well.

References:

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 STTR (R41/R42) and SBIR (R43/R44) grant mechanism(s). Applications may be submitted for support as Phase I, or Fast-Track Phase I/Phase II grants as described in the SBIR/STTR Omnibus Solicitation. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and the SBIR/STTR Omnibus Solicitation.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing-continuation applications based on this project will compete with all SBIR/STTR applications and will be reviewed according to the customary peer review procedures. The anticipated award date is (March 1, 2006) . Applications that are not funded in the competition described in this RFA may be resubmitted as NEW SBIR/STTR applications using the standard receipt dates for NEW applications described in the current SBIR/STTR Omnibus Solicitation.

This funding opportunity uses just-in-time concepts. Effective with the release of the PHS 2005-2 SBIR/STTR Omnibus Solicitation, the modular budget format is no longer accepted for SBIR/STTR grant applications. Applicants must complete and submit budget requests using Form Page 4 and Form Page 5.

2. Funds Available

The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines of funding support and project duration periods for SBIR and STTR Phase I and Phase II awards.

The NIAAA intends to commit approximately 1 million dollars in FY 06 to fund 3-6 Phase I or Fast-Track Phase I/Phase II applications under the SBIR/STTR set-aside funding mechanism. Fast-Track applications will benefit from expedited evaluation of progress following the Phase I feasibility study for transition to Phase II funding for expanded developmental work. Although the financial plans of the IC provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, it is not known if competing renewal applications will be accepted and/or if this RFA will be reissued.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation. Only U.S. small business concerns are eligible to submit SBIR/STTR applications. A small business concern is one that, on the date of award for both Phase I and Phase II agreements, meets ALL of the criteria as described in the current SBIR/STTR Omnibus Solicitation.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

On an SBIR application, the principal investigator must have his/her primary employment (more than 50%) with the small business at the time of award and for the duration of the project. The PI on an STTR application may be employed with the small business concern or the participating non-profit research institution as long as s/he has 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.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

The NIH will accept as many "different" applications as the applicant organization chooses. However, 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. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and the SBIR/STTR Omnibus Solicitation.

Section IV. Application and Submission Information

1. Address to Request Application Information

Application submission instructions are contained in Part I of the SBIR/STTR Omnibus Solicitation available from the NIH Small Business Funding website http://grants.nih.gov/grants/funding/sbir.htm. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Prepare all SBIR/STTR applications (new and revised) using the most current PHS 398 research grant application forms in accordance with the instructions provided in the SBIR/STTR Omnibus Solicitation. Applications must have a D&B Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

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

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

3.A. Receipt, Review and Anticipated Start Dates

Letters Of Intent Receipt Date(s): June 17, 2005
Application Receipt Dates(s): July 15, 2005
Peer Review Date(s): October/November, 2005
Council Review Date(s): January, 2006
Earliest Anticipated Start Date: March 1, 2006

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 IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Karen P. Peterson, Ph.D., SBIR Coordinator
Acting Chief, Research Policy and Special Programs Branch
Office of Scientific Affairs, NIAAA
5635 Fishers Lane MSC 9304
Bethesda, MD 20892-9304
Phone: 301-451-3883
Fax: 301-443-7043
Email: kpeterso@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

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

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

Tina Vanderveen, Ph.D.
Extramural Project Review Branch
Office of Extramural Acitivities
Attn: RFA-AA-06-001
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Telephone: (301) 443-2531
Fax: (301) 443-6077

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. Personal deliveries of applications are no longer permitted.

3.C. Application Processing

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

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

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

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

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

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

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

6. Other Submission Requirements

Plan for Sharing Research Data

Applicants requesting $500,000 or more in direct costs in any year should include a brief one paragraph description of how final research data will be shared, or explain why data-sharing is not possible. The specific nature of the data to be collected will determine whether or not the final dataset may be shared. If the final data are not amenable to sharing, for example, if they are proprietary, this must be explained in the application. Under the Small Business Act, SBIR/STTR grantees may withhold their data for four years after the end of the award. The Small Business Act provides authority for NIH to protect from disclosure and nongovernmental use all SBIR/STTR data developed from work performed under an SBIR/STTR funding agreement for a period of 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/STTR award, or by agreement between the small business concern and NIH. Applicants are encouraged to discuss their data-sharing plan with the Institute/Center staff likely to accept assignment of their application.

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. For more information on data sharing see http://grants.nih.gov/grants/policy/data_sharing/.

Sharing Research Resources

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

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

Section V. Application Review Information

1. Criteria

Applications received in response to this RFA will be reviewed by a peer review committee convened by NIAAA. This RFA strongly encourages the collaboration between alcohol researchers and non-alcohol researchers with expertise in the fields of genomics, proteomics, metabolomics, and bioinformatics. The principal investigator of an application is not required to be an active alcohol researcher. The applications that propose only to catalog the expression of RNA, protein, or metabolite as their final goal will not be considered to be responsive to this RFA. In addition, applications proposing further characterization of known alcohol biomarkers will be considered non-responsive as well.

2. Review and Selection Process

Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the (IC). Incomplete applications will not be reviewed. If the application is non-responsive to the funding opportunity, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

Applications submitted for this funding opportunity will be assigned to a Scientific Review Group on the basis of established PHS referral guidelines. Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.

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 SBIR and 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.

The 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.

All SBIR/STTR Applications

Significance: Does the proposed project have commercial potential to lead to a marketable produce or process? Does this study address an important problem? What may be the anticipated commercial and societal benefits of the proposed activity? If the aims of the application are achieved, how will scientific knowledge be advanced? Does the proposal 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? What will be the effect of these studies on the concepts or methods that drive this field?

Approach: Are the conceptual 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? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the milestones and evaluation procedure appropriate?

Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?

Investigator: Is the principal investigator capable of coordinating and managing the proposed SBIR/STTR? Is the work proposed appropriate to the experience level of the principal investigator and other researchers, including consultants and subcontractors (if any)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed?

Environment: Is there sufficient access to resources (e.g., equipment, facilities)? Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support?

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 seven areas described in the Research Plan, item J?

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. Failure to provide clear, measurable goals may be sufficient reason for the scientific review group to exclude the Phase II application from Fast-Track review.

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.

2.A. Additional Review Criteria:

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

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

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

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

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

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the percent effort listed for the PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

Period of Support: The appropriateness of the requested period of support in relation to the proposed research.

2.C. Sharing Research Data

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

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

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

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

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

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

The Notice of Grant Award (NGA) will be generated via e-mail notification from the awarding component, to the grantee business official. If a grantee is not e-mail enabled, a hard copy of the NGA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

2.A. Cooperative Agreement Terms and Conditions of Award
Not applicable

3. Reporting

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

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Q. Max Guo, Ph.D.
Division of Metabolism and Health Effect
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2118
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Phone: 301-443-0639
Email: qmguo@mail.nih.gov

Jose M. Velazquez, Ph.D.
Division of Metabolism and Health Effect
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2023
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Phone: 301-402-9408
Email: jvelazqu@mail.nih.gov

Lisa A. Neuhold, Ph.D.
Division of Neuroscience & Behavior,
National Institute on Alcoholism and Alcohol Abuse
5635 Fishers Lane, Room 2065, MSC 9304
Bethesda, MD 20892-9304
Phone: 301-594-6228
Fax: 301-443-1650
Email: lneuhold@mail.nih.gov

2. Peer Review Contacts:

Tina Vanderveen, Ph.D.
Acting Chief, Extramural Project Review Branch
Acting Director, Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Telephone: (301) 443-2531
FAX: (301) 443-6077
Email: tvanderv@mail.nih.gov

3. Financial or Grants Management Contacts:

Judy Fox
Chief, Grants Management Branch
Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Phone: (301) 443-4704
Fax (301) 443-3891
Email: jfox@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 (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

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

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

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

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

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

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

Public Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA 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.

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

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

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

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

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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