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 Diabetes and Digestive and Kidney Diseases (NIDDK) (http:/www2.niddk.nih.gov)

Title: Limited Competition: The Studies to Treat or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) (U01)

Announcement Type
This is a re-issue of RFAs DK-01-010 and DK-01-011.

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

Request For Applications (RFA) Number: RFA-DK-08-502

Catalog of Federal Domestic Assistance Number(s)
93.847, 93.848, 93.849

Key Dates
Release Date: April 18, 2008
Application Receipt Date: July 31, 2008
Peer Review Date: October 2008
Council Review Date : January 2009
Earliest Anticipated Start Date: March 1, 2009
Expiration Date: August 1, 2008

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(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, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
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

The purpose of this funding opportunity announcement (FOA) is to continue the support for the maintenance of the DCC and centers that have been conducting the TODAY and HEALTHY studies, as part of the STOPP-T2D (Studies to Treat or Prevent Pediatric Type 2 Diabetes) consortium. NIDDK invites applications for this limited competition Request for Applications (RFA) from eligible applicants. The program will fund, up to a maximum of 4 years, one U01 cooperative agreement award to complete the TODAY and HEALTHY studies and analyze collected data.

Background

Type 2 diabetes has traditionally been viewed as a disease of adults; however, recent epidemiological data reveal an increasing number of cases of type 2 diabetes in the pediatric population, especially among adolescents and in certain minority populations.  The increase of type 2 diabetes in children and adolescents is presumed to be a consequence of widespread obesity.

Clinical trials to develop effective primary prevention strategies, as well as effective treatment strategies are needed in the pediatric population. The Diabetes Prevention Program (DPP) demonstrated that intensified lifestyle or drug intervention in individuals with impaired glucose tolerance prevented or delayed the onset of type 2 diabetes.  However, interventions designed for adults may not be directly applicable to the pediatric population.  The majority of children with type 2 diabetes or at risk for type 2 diabetes are in the pre-adolescent or adolescent age range.  The adolescent period presents special challenges to health care providers and families when attempting to promote behavior and life style changes. 

When children develop diabetes, efficacious therapy is needed to maintain euglycemia in order to prevent the development of complications.  Diabetes is currently estimated to cost the U.S. health care system approximately $174 billion annually.  Much of the cost is related to the micro- and macrovascular complications of diabetes.  Since the development of complications is related, in part, to the duration of diabetes, children represent a population at high risk.  Indeed, studies have documented that from 30-50 percent of children with type 2 diabetes already have adverse cardiovascular risk profiles at the time of diagnosis. Unfortunately, the drugs currently approved for use in adults with type 2 diabetes have not been systematically studied in children.  Thus, treatment options for those children diagnosed with type 2 diabetes are restricted by the lack of data on the use of such pharmacological agents.

Prevention and treatment programs must also consider cultural differences among racial and ethnic groups that may influence acceptance of medical or lifestyle regimens.  This is especially important for type 2 diabetes in children, which disproportionately affects minority groups. 

In response to these concerns, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health funded the STOPP-T2D consortium. In response to a competitive RFA issued in 2000, awards to the DCC and 7 clinical sites were made in 2002 (U01 DK61230; U01 DK61231; U01 DK61223; U01 DK61249; (U01 DK61230; U01 DK61212; U01 DK61239; U01 DK61242; U01 DK61254). Investigators at these sites developed two studies: TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth), a treatment trial, and HEALTHY, a primary prevention study. Both studies utilize the same DCC and have benefited by being part of the STOPP-T2D consortium, because of the overlapping expertise required for the two studies.

TODAY

A consortium of 4 clinical centers (CC) and a coordinating center began protocol development. During protocol development, it was appreciated that additional CC would be required in order to be appropriately powered to conduct the intervention. An additional 11 CC were added in 2002 as subcontracts to the DCC by a competition comparable to NIH peer review. Following publication of a notice of opportunity to compete, full applications were peer reviewed by an external committee set up by the DCC using processes similar to an NIH review.

The TODAY study seeks to identify the best treatment for type 2 diabetes in children and teens. Participants will be randomly assigned to one of three treatment groups: metformin alone; metformin and rosiglitazone in a fixed dose combination; and metformin plus intensive lifestyle change aimed at losing weight and increasing physical activity. The TODAY study will enroll 750 children and teens 10 to 17 years old diagnosed with type 2 diabetes in the past 2 years. All subjects will be followed for a minimum of two years. All subjects will receive standard diabetes education. TODAY is testing the hypothesis that initial aggressive therapy will provide better glycemic control than traditional, step-wise therapy. This could potentially have long-lasting benefits in adolescents who may be thrown into diabetes by pubertal insulin resistance.

The TODAY study's main goal is to determine how well and for how long each treatment approach controls blood glucose levels. The primary outcome will be time to treatment failure, defined as a hemoglobin A1c > 8.5% for 6 months.  Secondary outcomes include measures of beta cell function and insulin resistance, body composition, nutrition, physical activity and fitness, microvascular complications, cardiovascular risk factors, side effects, quality of life, and psychological outcomes. The influence of individual and family behaviors on treatment response and the relative cost effectiveness of the treatment arms are also evaluated.

The TODAY study group has been successful in establishing the infrastructure required to conduct a complex, multi-center clinical trial. Recruitment networks have been set up so that youth with type 2 diabetes who are being cared for outside of a specific funded academic medical center can be recruited to the study. To date, approximately 600 children have been enrolled in TODAY. The TODAY cohort is 35% Hispanic American, 33% African American and 5% American Indian.

The TODAY study started later than expected because of the need to add additional sites to have adequate power and because of delays in acquiring study drug. Recruitment began in May 2004. Recruitment has been challenging because the majority of families targeted are extremely disadvantaged. Currently, enrollment is proceeding at a steady pace of 15 subjects/month, and is expected to be completed November 2008. The current awards end February 2009. The study will need to be extended to complete the minimum 2-year follow-up of the last subjects randomized and conduct data analysis.

The protocol has been approved at the IRBs of all participating sites.

HEALTHY

A consortium of 3 field centers and a coordinating center collaborated in a series of feasibility and pilot studies in preparation for the HEALTHY study. During protocol development, it was appreciated that additional field centers would be required in order to be appropriately powered to conduct the intervention. An additional 4 field centers were added in 2004 as subcontracts to the DCC by a competition comparable to NIH peer review. Following publication of a notice of opportunity to compete, full applications were peer reviewed by an external committee set up by the DCC using processes similar to an NIH review.

The HEALTHY study will determine if changes in school food services and physical education classes, along with activities that encourage healthy behaviors, lower risk factors for type 2 diabetes in middle school children. The study is being conducted in 42 middle schools (6 per field center). Participating schools have been randomly assigned to a program group, which implements the changes, or to a comparison group, which continues to offer food choices and PE programs typically seen in middle schools across the country.  Students in the program group will have: 

The study focuses on reducing three modifiable risk factors related to adiposity and glycemic dysregulation:  BMI percentile > 85 (indicating overweight), fasting glucose, and fasting insulin. 

Following the completion of pilot testing from 2003-2005, the HEALTHY study began in the fall 2006. The HEALTHY study group was successful in recruiting the required number of schools with the characteristics delineated in the protocol, and was successful in recruiting the cohort of students needed to conduct the study. Over 6400 6th graders participated in the baseline assessment. The cohort is 80% minority. Following baseline assessment in fall 2006, the intervention began in January 2007. The HEALTHY program is implemented in the 6th grade and continues for the 6th grade cohort as they progress through 7th and 8th grade. Final data collection occurs in the 2nd semester of 8th grade.

All students are exposed to the intervention since the HEALTHY program becomes part of the school curriculum. Students must provide parental consent and their own assent for data collection procedures. The protocol has been approved at the IRBs of all participating sites. At baseline and after 2.5 years, students will be tested for diabetes risk factors, including blood levels of glucose, insulin, and lipids.  They will also be measured for fitness level, blood pressure, height, weight, and waist circumference.

The HEALTHY study is currently being implemented in the 7th grade. Because of the need to

add additional field centers, and because the funding cycle and the school year are not matched, the current grants will end after the fall semester of 8th grade. Therefore, extension of the HEALTHY study is required to complete the intervention and data collection, and to analyze the collected data.

Objectives and Scope

The overall objective of the solicitation is to allow completion of the TODAY and HEALTHY studies.

For TODAY, this FOA will allow:  1) the clinical centers to complete the TODAY study and conduct outcomes assessment; 2) the DCC to continue to coordinate the activities of the TODAY research consortium, and clean and analyze the collected data; and 3) the TODAY investigators to write manuscripts describing the intervention and reporting the results of the TODAY study. It is expected that the TODAY study will provide important information about the best ways to treat type 2 diabetes in youth. In addition, the TODAY cohort will provide invaluable information about the natural history of type 2 diabetes in children and adolescents. Finally, ancillary studies to TODAY may enhance knowledge of the etiology and pathogenesis of early-onset type 2 diabetes.

While the project period for applications solicited under the invitation will be 4 years, it is anticipated that there may be an opportunity for extension of the consortium to allow additional follow-up of the cohort under study for an appropriate duration to better understand the natural history of type 2 diabetes in youth, particularly changes in beta cell function over time and the development of complications.

For HEALTHY, this FOA will allow: 1) the field centers to complete the intervention in the 8th grade and conduct the post-intervention outcomes assessment; 2) the DCC to continue to coordinate the activities of the HEALTHY research consortium, and clean and analyze the collected data; and 3) the HEALTHY investigators to write manuscripts describing the intervention and reporting the results of the HEALTHY study.

In addition to assessing the efficacy of a school-based primary prevention program for diabetes risk factors, it is expected that the HEALTHY study will provide important epidemiologic data about the health of middle school youth, especially is it relates to the presence and natural history of obesity and other risk factors of type 2 diabetes and cardiovascular disease.

Study Design

TODAY

The TODAY cooperative study group, comprised of investigators from the clinical centers, the DCC and the NIDDK, has jointly developed the standardized protocol. The three treatment regimens are:  (1) metformin alone, (2) metformin plus rosiglitazone, and (3) metformin plus an intensive lifestyle intervention called the TODAY Lifestyle Program (TLP).  Patients are randomized within two years of the diagnosis of T2DM.  The study is a randomized, controlled, partly double-blinded clinical trial. The intensive lifestyle arm is not blinded to either subject or investigator; however, the two medication arms are double-blinded.

The primary objective of the TODAY trial is to compare the three treatment arms on time to treatment failure in 750 patients (250 per arm) enrolled from 10 to 17 years of age with T2DM.  The study is powered to allow all three possible comparisons between the treatment groups while maintaining the overall significance level at 0.05. 

The primary objective of the TODAY trial is to compare the efficacy of the three treatment arms on time to treatment failure based on glycemic control.  The secondary aims are to: compare and evaluate the safety of the three treatment arms; compare the effects of the three treatments on the pathophysiology of T2DM with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes; evaluate the influence of individual and family behaviors on treatment response; and compare the relative cost effectiveness of the three treatment arms.

The primary outcome of treatment failure is defined in terms of HbA1c, because it correlates with glycemic control and long-term diabetes outcome.  There are a number of secondary outcomes in this trial.  The results of these secondary outcomes help interpret the primary effect of the treatment regimens on HbA1c.  These secondary aims have been chosen because they provide insight into the mechanism by which the treatment regimens affect durable glycemic control (e.g., effects on insulin resistance, sensitivity, diet and physical fitness) or because they provide information concerning the differential risks and benefits of the three treatment arms (e.g., studies of microvascular complications and cardiovascular risk). 

The TODAY consortium will jointly analyze data from the study, and disseminate this information through presentations at scientific meetings and manuscripts in scholarly, peer-reviewed journals. The study group has also developed mechanisms to solicit research proposals from investigators outside the consortium who may have novel hypothesis they wish to test in the TODAY cohort or by using TODAY samples and/or data. TODAY is collecting specimens that include sufficient material for measurements to be made based on the hypotheses developed by the TODAY study group and also for storage of sufficient specimens so that materials will be available in the future when new technology or approaches to type 2 diabetes research may become available.

Study Components

One award will be made to the DCC, which will include subcontracts to each of the 15 clinical centers conducting the TODAY study, and to the central laboratory, reading centers, and cores.

1. Clinical Centers

Up to 15 subcontracts to the DCC will be made for the clinical centers that are responsible for conducting the intervention and for collecting outcomes in TODAY subjects.

The CC will be expected to implement the intervention, according to the established TODAY protocol. The CC will collect data in accordance with established study procedures and submit all samples and data to the DCC and central laboratory and central reading centers, as appropriate and required by the protocol.

Investigators at the CC will conduct analyses in conjunction with the DCC. The TODAY consortium will have exclusive access to data from the TODAY study population for a period of time, in accordance to a timetable determined by the TODAY Steering Committee in conjunction with NIDDK. The TODAY study group will then share data and patient specimens derived from the TODAY study through the NIDDK repository. The TODAY Steering Committee has already established policies under which ancillary studies may be conducted while the study is ongoing.

2. Data Coordinating Center (DCC)

There will be a single DCC. The DCC is responsible for the collection, management and analysis of all clinical and laboratory data. The DCC will continue to be responsible for ensuring subject confidentiality and safety, and quality control. The DCC will conduct training and certification of study staff, and maintain and update the manual of operations. The DCC will continue to oversee implementation of and adherence to the study protocol. The DCC will coordinate communication among and with the CC.

The DCC will continue to coordinate movement of biologic samples from the CC to the central laboratory and, subsequently, to the NIDDK repository, where samples will be stored for future analysis. The DCC will similarly continue to coordinate the flow of radiographic tests and other collected data to the appropriate central reading center. The DCC will also coordinate with the NIDDK Data Repository to prepare all TODAY data for eventual archiving and distribution.

The DCC will provide biostatistical, data management and analytic expertise. The DCC will continue to prepare appropriately detailed reports to the Steering Committee and to the TODAY DSMB, and to the NIDDK staff at regular intervals. The DCC will be responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees.

3. Steering Committee

The primary governing body of the study will continue to be the Steering Committee, comprised of the Principal Investigators of the DCC and each CC, and the NIDDK Project Scientist.

The Steering Committee will continue to develop policies and procedures for the TODAY study group, and ensure that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection, and other performance measures.

4. Project Scientist

The NIDDK Project Scientist will continue to assist the Steering Committee in carrying out the TODAY study. The Project Scientist will provide scientific support to awardees’ activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications, and overall performance monitoring.

HEALTHY

The HEALTHY cooperative study group, comprised of investigators from the 7 field centers, the DCC and the NIDDK, has jointly developed the standardized protocol. The study is a primary prevention cluster design trial.  The focus is on the public health impact of the intervention.  The school is the unit of sample size determination, randomization, intervention, and analysis.  Observations are made and data collected at the school, grade, class, and student levels.

The study started at the beginning of school year 2006-2007 gathering baseline data collection on 6th graders.  The students attended a health screening to collect height, weight, waist circumference, and blood pressure.  Fasting blood was drawn and shipped to a central laboratory for analysis of insulin, glucose, and lipids (total cholesterol, HDL, LDL, triglycerides).  The students also completed self-report questionnaires on pubertal development (Tanner stage), health utility index (HUI), visual-analog health thermometer (EuroQoL), 2-day self-administered physical activity checklist (2D-SAPAC), and food frequency questionnaire (Block FFQ).  Other data collected are:  student fitness (20-meter shuttle test) and behavior self-assessments; economic cost-effectiveness; school food environment production, sales, servings, and item-based nutrient analysis; school academic performance (standard test scores, attendance, comportment); and environmental influences on student health above and beyond the study intervention.   Interim data collection of height and weight occurs at the end of 7th grade and end of study data collection occurs at the end of 8th grade (repeat of baseline).  All students must provide parental consent and their own assent for data collection procedures. 

In those schools randomized to intervention, the intervention started in the second half of 6th grade and continues as the students progress through their 7th and 8th grades.  The four intervention components are integrated to deliver the theme each semester.  The intervention components are:

1.         Nutrition.  This component is designed to change the nutritional quality of food and beverage offerings throughout the total school food environment, including cafeteria meals and after school snacks offered through federal programs such as the National School Lunch Program (NSLP) and School Breakfast Program (SBP), a la carte (snack bars and student stores) sales, and vending machines.

2.         Physical Education.  This component makes changes in the physical education (PE) program and equipment to increase both participation and number of minutes spent in moderate-to-vigorous physical activity when implemented by PE teachers as part of classroom lesson plans. 

3.         Behavior.  This component is comprised of brief classroom activities designed to increase knowledge, enhance decision-making skills, promote peer involvement and interaction, and enhance social influence.  It uses individual and group behavior change initiatives aimed at promoting healthier behaviors through self monitoring, goal setting, and problem solving.  Parents and family members are provided with information and strategies to support youth in accomplishing behavioral goals.

4.         Communications.  School-wide campaigns enhance and promote changes in nutrition, activity, and behavior.  The campaigns provide core materials and actions.  Events are designed to offer sites regional, cultural, and operational flexibility. 

Study Components

One award will be made to the DCC, which will include subcontracts to each of the 7 field centers conducting the HEALTHY study, and to central laboratory and cores.

1. Field Centers

Up to 7 subcontracts to the DCC will be made for the field centers that are responsible for conducting the intervention at the 21 HEALTHY intervention schools and for collecting outcomes and process data at all 42 HEALTHY schools.

The field centers will be expected to implement the 8th grade intervention, according to the established HEALTHY protocol. The field centers will collect data in accordance with established study procedures and submit all samples and data to the DCC and central laboratory, as appropriate and required by the protocol.

Investigators at the field centers will conduct analyses in conjunction with the DCC. The HEALTHY consortium will have exclusive access to data from the HEALTHY study population for a period of time, in accordance to a timetable determined by the HEALTHY Steering Committee in conjunction with NIDDK. The HEALTHY study group will then share data and patient specimens derived from the HEALTHY study through the NIDDK repository. The HEALTHY Steering Committee has already established policies under which ancillary studies may be conducted while the study is ongoing.

2. Data Coordinating Center (DCC)

There will be a single DCC. The DCC is responsible for the collection, management and analysis of all clinical and laboratory data. The DCC will continue to be responsible for ensuring subject confidentiality and safety, and quality control. The DCC will conduct training and certification of study staff, and maintain and update the manual of operations. The DCC will continue to oversee implementation of and adherence to the study protocol. The DCC will coordinate communication among and with the field centers.

The DCC will continue to coordinate movement of biologic samples from the field centers to the central laboratory and, subsequently, to the NIDDK repository, where samples will be stored for future analysis. The DCC will also coordinate with the NIDDK Data Repository to prepare all HEALTHY data for eventual archiving an distribution.

The DCC will provide biostatistical, data management and analytic expertise. The DCC will continue to prepare appropriately detailed reports to the Steering Committee and to the HEALTHY DSMB, and to the NIDDK staff at regular intervals. The DCC will be responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees.

3. Steering Committee

The primary governing body of the study will continue to be the Steering Committee, comprised of the Principal Investigators of the DCC and each field center, and the NIDDK Project Scientist.

The Steering Committee will continue to develop policies and procedures for the HEALTHY study group, and ensure that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection, and other performance measures.

4. Project Scientist

The NIDDK Project Scientist will continue to assist the Steering Committee in carrying out the HEALTHY study. The Project Scientist will provide scientific support to awardees’ activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications, and overall performance monitoring.

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NIH cooperative Agreement (U01) award mechanism(s).
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". It is not known whether this cooperative agreement will be continued beyond the initial award period.

2. Funds Available

The NIDDK intends to make one award to the STOPP-T2D coordinating center for up to $26 million in FY2009. This award will include subcontracts to the 15 TODAY clinical sites and the 7 HEALTHY field centers. The applicant may request a project period of 4 years.  Future year amounts will depend on annual appropriations.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies as described in the DK-01-010 and 01-011. Only the STOPP-T2D DCC is eligible to submit an application.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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 support.

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

Resubmission applications are not allowed in response to this FOA.

Competing renewal applications are allowed in response to this FOA.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Additional information is available in the PHS 398 grant application instructions.

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
Application Receipt Date: July 31, 2008
Peer Review Date: October 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: March 1, 2009

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

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

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

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

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

Francisco Calvo, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 752
Bethesda, MD 20892
Telephone: (301) 594-8885
FAX: (301) 480-3505
Email: fc15y@nih.gov

For express/courier service use 20817

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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 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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 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 NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements and Information

The awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Appendix Materials

All paper PHS 398 applications submitted for May 25, 2008 and subsequent due dates must provide appendix material on CD only, and include five identical CDs in the same package with the application.  Paper applications submitted for due dates prior to May 25, 2008 may voluntarily provide the appendix on five identical CDs; if submitting CDs it is not necessary to include a paper appendix. (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

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.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

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 the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIDDK and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The following will be considered in making funding decisions:

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

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

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?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

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 rating:

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 on Human Subjects in the PHS 398 instructions).

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 on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

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

2.B. Additional Review Considerations

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

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing Plan(s)   

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information


1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/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).

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for all aspects of development and implementation of the protocols, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.  Modifications of protocols will be approved by the Steering Committee. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.  The collaborative protocol and governance policies will call for the continued submission of data centrally to the DCC for a collaborative database, the submission of copies of the collaborative data sets to each principal investigator upon completion of the study, procedures for data analysis, reporting and publication, and procedures to protect and ensure the privacy of medical and genetic data (if any) and records of individuals.  The NIDDK Project Scientist, on behalf of the NIDDK, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.  The NIDDK expects that biologic samples and associated clinical data will be made available to the broader scientific community at an appropriate juncture to support further studies related to the prevention and etiology of type 2 diabetes and obesity. The study will be expected to put all study materials and procedures manuals in the public domain and/or make them available to other investigators. Awardees are encouraged to publish and to publicly release and disseminate results, data and other products of the study, concordant with the study protocol and governance and the approved plan for making data and materials available to the scientific community and the NIDDK and other co-sponsors. 

Support or other involvement of industry or any other third party in any study performed by the Consortium may be advantageous and appropriate.  However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification to, and concurrence, by NIDDK.

The NIDDK has established Central Biosample, Genetic and Data Repositories for the archival and storage of data and biosamples. All samples and data transferred to the repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. The clinical and field centers will submit the samples and data to the NIDDK repository via the DCC and the study is expected to put all study design materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NIDDK, for the conduct of research at no charge other than the costs of reproduction and distribution.

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

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NIDDK Project Scientist will have one vote on the Steering Committee and on all key study group subcommittees. The Project Scientist will have substantial scientific-programmatic involvement in quality control, interim data analysis, safety monitoring, and final data analysis and interpretation, preparation of publications, and coordination and performance monitoring.  The dominant role and prime responsibility for these activities resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the Project Scientists.

The NIDDK reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NIDDK cannot concur, (d) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (e) human subject ethical issues that may dictate a premature termination.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.

2.A.3. Collaborative Responsibilities

The Steering Committee for each study, composed of each of the Principal Investigators of the clinical centers (TODAY) or field centers (HEALTHY) and the DCC, and the NIDDK Project Scientist, and the Chairman of the Steering Committee, will be the main governing board of the study.  This committee will have the primary responsibility for approval of the common protocols, facilitating the conduct of participant follow-up, monitoring completeness of data collection and timely transmission of data to the DCC, and reporting the study results.  It will also be responsible for establishing study policies in such areas as access to patient data, ancillary studies, publications and presentations, and performance standards.  Each member of the Steering Committee will have one vote and all major scientific decisions will be determined by a majority vote of the Steering Committee.  A Chairperson will subsequently be chosen from among the Steering Committee members (but not the NIDDK Project Scientist).   Subcommittees will be established for specific purposes as needed, such as for ancillary studies, publications and presentations, quality control, recruitment, protocol adherence, among others. 

Each Consortium awardee agrees to the governance of the study through the Steering Committee.  The Steering Committee voting membership shall consist of the Principal Investigators of the field centers (HEALTHY) or clinical centers (TODAY) and the DCC, and the NIDDK Project Scientist.  Meetings of the steering Committee will ordinarily be held by telephone conference calls or be face to face.

The NIDDK Project Scientist may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., to address issues of recruitment, intervention, follow-up, quality control, standards and methods, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment or retention. 

An independent DSMB convened by the NIDDK and composed of experts in relevant medical, psychological, statistical, operational, and bioethical fields who are not otherwise involved in the study will be established to review periodically the progress of the study.  The committee will oversee participant safety, evaluate study progress and results, monitor data quality, and provide operational and policy advice to the Steering Committee and the NIDDK regarding the status of the study.  The Principal Investigator of the Data Coordinating Center, the NIDDK Project Coordinator, and the Director of the Division of Diabetes, Endocrinology and Metabolism may participate as ex-officio, non-voting members of the DSMB.  DSMB members will be appointed by the Director, NIDDK. The NIDDK named Project Coordinator will serve as executive secretary of the External Advisory Board.

The NIDDK expects that biologic samples and associated clinical data will be made available to the broader scientific community at an appropriate juncture to support further studies related to the prevention and etiology of type 2 diabetes and obesity. The NIDDK expects that STOPP-T2D will put all study materials and procedures manuals in the public domain and/or make them available to other investigators via the NIDDK central repository according to the timetable determined by the steering committee in concordance with NIDDK.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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:

Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 699
Bethesda, MD 20892
Telephone: (301) 594-0021
FAX: (301) 480-3503
Email: linderb@mail.nih.gov

2. Peer Review Contacts:

Francisco Calvo, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda , MD 20892
Telephone: (301) 594-8885
FAX: (301) 480-3505
Email: fc15y@nih.gov

3. Financial or Grants Management Contacts:

Chris Davis
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room  700
Bethesda, MD 20892
Telephone: (301) 594-2115
FAX: (301) 594-9523
Email: davisch@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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 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 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



NIH Office of Extramural Research Logo
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®



Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.