RELEASE DATE:  September 10, 2002

PA NUMBER: PA-02-165

EXPIRATION DATE: After February 1, 2006, unless reissued

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
National Institute of Neurological Disorders and Stroke (NINDS) 
National Eye Institute (NEI) 
National Institute of Nursing Research (NINR)
National Heart, Lung, and Blood Institute (NHLBI)


o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations


The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 
the National Institute of Neurological Disorders and Stroke (NINDS), the 
National Eye Institute (NEI), the National Institute of Nursing Research 
(NINR), and the National Heart, Lung, and Blood Institute (NHLBI) seek 
research to understand racial/ethnic disparities in the development of the 
microvascular (nephropathy, retinopathy, and neuropathy), and macrovascular 
(cardiovascular disease and stroke) complications of diabetes.

This program announcement replaces PAS-00-028.



Racial and ethnic groups differ considerably in the frequency of diabetes in 
their populations. For example, rates of type 2 diabetes are particularly 
high among American Indians, African Americans, Hispanic Americans, and Asian 
and Pacific Islanders.  The microvascular complications of diabetes are a 
major problem in these groups, not only because their frequency of diabetes 
is high, but also because there is evidence that complications occur more 
frequently among individuals with diabetes in these minority populations. 
However, the reasons for these differences are not well understood.

The Diabetes Control and Complications Trial (DCCT), for type 1 diabetes, and 
the United Kingdom Prospective Diabetes Study (UKDPS), for type 2 diabetes, 
established the importance of intensive diabetes control in dramatically 
reducing the devastating complications that result from poorly controlled 
diabetes.  Both the DCCT and the UKPDS demonstrated the efficacy of intensive 
glucose control in reducing the risk for the microvascular complications of 
diabetes, such as retinopathy, neuropathy, and nephropathy. In addition, 
numerous studies have recently demonstrated that intensive blood pressure 
control is essential in preventing both micro- and macrovascular 
complications of diabetes. Aggressive management of dyslipidemia has also 
been shown to decrease macrovascular complications.  Some of the racial 
differences in diabetic complications may be explained by differences in 
availability and quality of health services.  There may be differences by 
race/ethnicity and socioeconomic status in self-care practices, health care 
provider practices, and/or access to quality health care and prevention 
services that directly impinge on the frequency and magnitude of risk factors 
for diabetes complications and the intensity of medical care for early stages 
of complications to prevent progression to end-stage disease. 

In addition to differences in blood glucose, lipid and blood pressure 
control, which may be modified by improved medical care, genetic 
susceptibility and other biological risk factors may contribute in unknown 
ways that lead to complications.  This is suggested by the clustering of 
complications (especially nephropathy) within families and by the excess risk 
of retinopathy in Hispanics versus non-Hispanics that remains when the degree 
of hyperglycemic exposure is taken into account.

Finally, lifestyle, psychosocial factors, stress, family structure, social 
support, diet and culture, and socioeconomic status vary among racial and 
ethnic minorities and may contribute to differential risk of developing 
diabetes complications and progression of complications.  Little is known 
about how these behavioral factors influence the risk of complications and 
the effectiveness of interventions designed to prevent or reduce diabetes 
complications in racial and ethnic minority groups.

Identification of these divergent etiologies and quantification of their 
correlation to risk have important implications for prevention and 
amelioration of microvascular complications.  Such information might improve 
the effectiveness of treatment to reduce the disparities in the incidence in 
diabetes complications among racial and ethnic groups.

In contrast to microvascular complications, racial and ethnic minorities with 
diabetes often have lower rates of macrovascular disease than Caucasian 
population groups.  Angina, myocardial infarction, and other forms of 
coronary heart disease appear to be less common in African Americans, Mexican 
Americans and Native Americans than in non-Hispanic whites. This difference 
is particularly striking given the higher incidence of diabetes in these 
populations. The factors that account for the differing macrovascular disease 
rates are unknown. For example, the relative contribution  of glycemia 
(versus other risk factors) to cardiovascular risk in these minority 
populations has not been studied. 

Objectives and Scope

The overall objective of this Program Announcement is to understand 
racial/ethnic disparities in the development of the micro- and macrovascular 
complications of diabetes. It is recognized that both biologic and non-
biologic factors may be operating in these populations.
Approaches may include metabolic, genetic and/or epidemiologic studies in 
representative populations. Advantage might be taken of extant cohort studies 
that have been established for investigation of diabetes or other diseases.  
Collaboration among investigators of these established cohorts would be 
desirable, so that these studies might jointly develop protocols and evaluate 
findings.  Alternatively, investigators may propose to start a new cohort, 
appropriately powered, to capture the current risks and outcomes in the era 
of new medications for glucose, blood pressure and lipid control.  Such 
studies of current risks might appropriately be based in large HMOs or 
clinical practices with structure and data management practices conducive to 
efficient and cost-effective analyses.

Investigators are encouraged to incorporate appropriate surrogate markers for 
complications into study design to shorten the duration of studies. Such 
surrogate markers might include early indicators of end-stage complications 
(background retinopathy, albuminuria, serum creatinine, basement membrane 
thickening, EKG, carotid ultrasound). 

Appropriate topics for investigation would include but are not limited to:

o   Epidemiologic studies to determine the rates of microvascular 
(nephropathy, retinopathy, and neuropathy) and macrovascular (cardiovascular 
disease and stroke) diabetic complications in appropriate representative 
samples of contemporary populations.

o   Studies to identify genes which might affect the development and 
progression of micro- and macrovascular complications in different 

o    State-of-the-art, hypothesis-driven metabolic studies to determine 
whether there are differences in metabolism, insulin sensitivity, energy 
expenditure, beta cell function, and body composition that might influence 
glycemic control and risk of complications in different populations.

o   Studies to compare the contribution of glycemia versus other risk factors 
(e.g., smoking, hyperlipidemia, body composition, blood pressure)  in the 
development of micro- and macrovascular disease in patients with diabetes, 
and to study how treatment of these factors may influence rates of 
development of complications in different racial/ethnic groups.

o   Studies to investigate environmental factors, such as medical care, 
behavior and lifestyle, and  socioeconomic status, that may contribute to 
risk for development and progression of complications.  Such studies could 
incorporate culturally-specific lifestyle factors into treatment and 
prevention strategies to reduce risk across racial and ethnic groups. 

o   Studies to determine whether different pathophysiologic mechanisms or 
risk factors are operative among subgroups within racial/ethnic minorities 
(e.g., different subgroups of Hispanic Americans, such as Mexican Americans, 
Puerto Ricans, Caribbean Hispanics, Cuban Americans).  

Understanding the basis for differing susceptibilities could provide 
information that would lead to specific therapies likely to be useful in 
various subpopulations at high risk for the development of diabetes 


This PA will use the National Institutes of Health (NIH) research project 
grant (R01) and the Exploratory/Development Research Grant (R21) award 
mechanisms. Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total project 
period for an R01 application submitted in response to this PA may not exceed 
5 years. 

The R21 awards are to demonstrate feasibility and to obtain preliminary data 
testing innovative ideas that represent clear departure from ongoing research 
interests. These grants are intended to: 1) provide initial support for new 
investigators; 2) allow exploration of possible innovative new directions for 
established investigators; and 3) stimulate investigators from other areas to 
lend their expertise to research within the scope of this solicitation. 
Applicants for the R21 must limit their requests to $125,000 direct costs per 
year and are limited to two years. These R21 grants will not be renewable; 
continuation of projects developed under this program will be through the 
regular research grant (R01) program.

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting format. (see 
https://grants.nih.gov/grants/funding/modular/modular.htm).   Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format. Otherwise, follow the instructions for non-
modular research grant application. 


You may submit (an) application(s) if your institution has any of the 
following characteristics:
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign


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. Investigators new to diabetes and 
digestive and kidney diseases are encouraged to apply. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are encouraged to apply for NIH programs.


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

Direct inquiries regarding programmatic issues to:

Kristin Abraham, Ph.D. 
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of  Diabetes and Digestive
   And Kidney Diseases
6707 Democracy Boulevard, Room 607
Bethesda, MD 20892-5460
Telephone:  (301) 451-8048
FAX:  (301) 480-3503
E-mail:  ka136s@nih.gov

Paul Nichols, Ph.D.
National Institute of  Neurological 
    Disorders and Stroke
Neuroscience Center, Room2118
6001 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 496-9964
FAX: (301) 401-2060
E-mail: pn13w@nih.gov

Peter Dudley, Ph.D.
Vision Research Program
National Eye Institute
Executive Plaza South, Rm. 350
Bethesda, MD  20892
Telephone: (301) 496-0484
FAX: (301) 402-0528
E-mail: pad@nei.nih.gov

Nell Armstrong, Ph.D.
Office of Extramural Programs
National Institute of Nursing Research
6701 Democracy Blvd, Rm 701
Bethesda, MD  20892-6300
Telephone: (301) 594-5973
FAX: (301) 480-8260
E-mail: nell.armstrong@nih.gov

Chuke E. Nwachuku, Ph.D.
Clinical Applications and Prevention Program
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 435-0418
FAX: (301) 480-1773
E-mail: chuke@nih.gov

Direct inquiries regarding fiscal matters to:

Charlette Kenley
Division of Extramural Activities
Grants Management Branch
National Institute of  Diabetes and Digestive
   And Kidney Diseases
6707 Democracy Boulevard, Room 723
Bethesda, MD 20892-5456
Telephone:  (301) 594-8847 
FAX:  (301) 480-3504
E-mail: ck128k@nih.gov

Karen Shields
Grants Management Branch
National Institute of  Neurological 
    Disorders and Stroke
Neuroscience Center, Room 3290
6001 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 496-9231
FAX: (301) 402-0129
E-mail: ks26n@nih.gov

William W. Darby
Chief, Grants Management Branch
National Eye Institute
Executive Plaza South, Suite 350
6120 Executive Blvd
Bethesda, MD 20892-7164
Telephone: 301-451-2020
FAX: 301-496-9997
E-mail: wwd@nei.nih.gov

Diane Drew
Office of Grants and Contracts Management
National Institute of Nursing Research
6701 Democracy Blvd, Rm 701
Bethesda, MD  20892-6300
Telephone: (301) 594-2807
FAX: (301) 451-5651
Email: diane_drew@nih.gov

Bob Pike
Grants Management Office
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD  20892
Phone: (301) 435-0172
FAX: (301) 480-3310
E-mail: rp28p@nih.gov


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at https://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.


All application instructions outlined in the PHS 398 application kit are to 
be followed, with the following requirements for R21 applications:  

1.  R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME" 
concepts, with direct costs requested in $25,000 modules, up to the total 
direct costs limit of $125,000 per year for a maximum of two years.  

2. Although preliminary data are not required for an R21 application, they 
may be included.

3.  Sections a-d of the Research Plan of the R21 application may not exceed 
15 pages, including tables and figures.  

4.  Appendix materials will not be accepted. 

Further details regarding the purpose and format of R21 applications can be 
found by reading the NINDS guidelines describing the R21 program 
(http://www.ninds.nih.gov/funding/r21guidelines.htm). All R21 applications 
submitted in response to this Program Announcement should follow the NINDS 
guidelines, regardless of Institute assignment. Applicants may also contact 
one of the Program Officials listed under "Inquiries" for further 
information. If there is other important information it should be included in 
the PA. 

direct costs in each year of $250,000 or less must be submitted in a modular 
grant format.  The modular grant format simplifies the preparation of the 
budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 


Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member who has agreed to 
accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:

1)  Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2)  Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and
3)  Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 
Expanded instructions for NHLBI investigators can be found at  

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five 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
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at 
https://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not 
accept any application in response to this PA that is essentially the same as 
one currently pending initial review unless the applicant withdraws the 
pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
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:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate national advisory council 
or board

Review Criteria 

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:

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

(1) Significance:  Does this study address an important problem?  If the aims 
of your application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) Approach: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Do you acknowledge potential problem areas and consider alternative 

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

(4) Investigator: Are you appropriately trained and well-suited to carry out 
this work? Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)? 

(5) Environment: Does the scientific environment in which your 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 

The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application. Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score. For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is 
essential to move a field forward.

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.

INCLUSION:  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.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the 
section on Federal Citations, below).

DATA SHARING:  The adequacy of the proposed plan to share data.

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.


Applications submitted in response to a PA will compete for available funds 
with all other recommended applications. The following will be considered in 
making funding decisions:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities



It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided 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 research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
October 9, 2001 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html; a 
complete copy of the updated Guidelines are available at 
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.


It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998. 

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 that is available at 

involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and audit procedures. In addition, it is NIH policy that 
all clinical trials require data and safety monitoring, with the method and 
degree of monitoring being commensurate with the risks (NIH policy for Data 
and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 


NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement 
dated June 5, 2000, at the following website: 


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:

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 


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. Reviewers are cautioned that 
their anonymity may be compromised when they directly access an Internet 


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 


This program is described in the Catalog of Federal Domestic Assistance No. 
93.847, 93.853, 93.867, 93.361, 93.837, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review. Awards are made under authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies described at
https://grants.nih.gov/grants/policy/policy.htm and under Federal Regulation 
42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-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, and 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.

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