HEALTH DISPARITIES IN NIDDK DISEASES

RELEASE DATE:  March 11, 2004

PA NUMBER:  PA-04-074  (see Amendment NOT-DK-04-015)

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Accordingly, this funding opportunity 
expires on the date indicated below. Replacement R01 (PA-06-182) and R21 (PA-06-183) 
funding opportunity announcements have been issued for the submission date 
of June 1, 2006 and submission dates thereafter. 

See NOT-OD-06-048 for information on May 1, 2006 Submission Date for AIDS and 
AIDS-related R03 and R21 Applications.

EXPIRATION DATE:  March 2, 2006

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:  
National Institute of Health (NIH)
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATIONS:  
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.847, 93.848 and 93.849 

THIS PA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS PA

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
seeks research to understand and mitigate issues of health disparities in 
high priority diseases within its scope, including diabetes, obesity, 
nutrition-related disorders, hepatitis C, gallbladder disease, H. Pylori 
infection, sickle cell disease, kidney diseases, and metabolic, 
gastrointestinal, hepatic, and renal complications from infection with HIV.

RESEARCH OBJECTIVES

Background

It is recognized that there are many diseases and disorders that 
disproportionately affect the health of racial and ethnic minority 
populations in the United States.  It is evident that African-Americans, 
Hispanic Americans, American Indians, Alaska Natives, some Asian-Americans, 
and Native Hawaiians and other Pacific Islanders experience much higher risks 
and poorer health status than the general population. 

Several of the diseases that disproportionately afflict minorities are high 
priority research areas for NIDDK, including diabetes, obesity, nutrition-
related disorders, hepatitis C, gallbladder disease, H. Pylori infection, 
sickle cell disease, kidney diseases, and metabolic, gastrointestinal, 
hepatic, and renal complications from infection with HIV.  NIDDK encourages 
efforts health disparity research to reduce the human and economic costs 
resulting from inequities in health care and health outcomes.

Specific examples of health disparities in these areas include the following:

Type 2 Diabetes:
o African-Americans, Hispanic/Latino Americans, American Indians, Alaska 
Natives, some Asian-Americans, Native Hawaiians and other Pacific Islanders 
are at particularly high risk for the development of type 2 diabetes. 
Diabetes prevalence rates among American Indians are two to five times those 
of whites. On average, African-American adults are 1.7 times as likely and 
Mexican-Americans and Puerto Ricans are twice as likely to have the disease 
as non-Hispanic whites of similar age. Japanese Americans and Samoans have 
elevated rates of diabetes.

o All patients with diabetes are at high risk for microvascular complications 
affecting the eyes, nerves, and kidneys; for lower extremity amputations; and 
for coronary heart disease. Patients with diabetes from racial and ethnic 
minorities are more likely to develop the microvascular complications of 
diabetes and to have more lower extremity amputations compared with non-
Hispanic white patients with diabetes. 

o Diabetes in pregnancy is associated with increased risk of congenital 
malformations and of complications during delivery and in the perinatal 
period.  Women from minority groups, especially American Indian women, are 
much more likely to have type 2 diabetes during their childbearing years.  In 
American Indian populations, maternal diabetes during pregnancy increases the 
risk of type 2 diabetes in childhood tenfold and is the most important risk 
factor for the development of type 2 diabetes in childhood. 

o Type 2 diabetes, once considered a disease of adults only, has been 
increasing in children and adolescents. Childhood diabetes clinics have 
reported that as many as one-third of their new onset diabetes patients have 
type 2 diabetes. More than three-quarters of these children are minorities.  
Rates of type 2 diabetes in adolescent Pima Indians have doubled in the past 
30 years. Type 2 diabetes in childhood and adolescence leads to the 
development of serious kidney, eye, and heart disease in young adulthood for 
many of these children. 

Obesity:
o Obesity is more common among minority individuals in the United States. 
More than 70 percent of African-American and Mexican-American women are 
overweight as defined by a body mass index (BMI) above 25.  The prevalence of 
obesity (BMI above 30) in the United States is increasing in all racial and 
ethnic groups, but it affects minority populations disproportionately. More 
than 15 percent of non-Hispanic black women are severely obese, with BMIs 
above 40.

o Rates of overweight in children and adolescents more than doubled from 1980 
to 2000 in the United States. Rates of obesity in American Indian children 
are more than twice as high as in the nation’s population as a whole. Obesity 
in childhood is associated with higher cholesterol levels and higher rates of 
hypertension, type 2 diabetes, orthopedic problems, and gallstone disease. 

End-stage renal disease:
o End-stage renal disease (ESRD) is a major public health problem in the 
United States.  The adjusted incidence rate has steadily increased over the 
past decade, from 238 per million population in 1992 to 334 in 2001. 
Similarly, the adjusted point-prevalence rate has increased from 886 per 
million population in 1992 to 1,392 in 2001. There are striking racial and 
ethnic differences in the incidence and prevalence rates. Racial/ethnic 
minorities, specifically African-Americans, American Indians and Alaska 
Natives, Native Hawaiians and other Pacific Islanders, and Hispanic 
Americans, have disproportionately greater incidence and prevalence rates. 
For example, in 2001 the incidence rates were 254 per million population in 
Caucasians, 988 per million in African-Americans, 395 per million in Asian-
Americans and Native Hawaiians and other Pacific Islanders, and 696 per 
million in American Indians and Alaska Natives. Eleven percent of all new 
ESRD patients were Hispanic Americans.

o The four leading causes of ESRD include diabetes mellitus (primarily type 
2), hypertension, glomerulonephritis, and cystic renal disease. However there 
is significant variability in the cause of ESRD among the various racial and 
ethnic groups.  Diabetic nephropathy is a predominant cause of ESRD in all 
racial and ethnic groups.  However, the rate of diabetic nephropathy is 
highest in American Indians and Alaska Natives. Hypertensive nephropathy is 
more prevalent in African-Americans than in other groups. 

o Other diseases causing ESRD in which African-Americans and other racial and 
ethnic minorities show a disproportionate increase over Caucasians include 
systemic lupus erythematosus; focal and segmental glomerulosclerosis, 
especially in children; and AIDS.

Hepatitis C and Liver Disease:
o Hepatitis C affects 1.5 percent of the U.S. population and is twofold to 
threefold more common among African-Americans and Hispanic Americans than 
among Caucasians. 

o Therapy for hepatitis C is evolving; current recommended regimens are 
effective in only 40 percent of patients. The response rate in African-
Americans is lower than in Caucasians. 

o The only therapy for end-stage liver disease is liver transplantation. At 
present, approximately 4,000 liver transplants are done yearly, but waiting 
lists are lengthening, and a shortage of organs has caused an increase in 
deaths among patients awaiting transplantation. Although end-stage liver 
disease is more common in minority individuals, those individuals are less 
likely to undergo liver transplantation. After liver transplantation, the 
survival rate appears to be lower for African-Americans than for Caucasians.

Aquired immuno-deficiency syndrome (AIDS):
o More than 600,000 persons have been diagnosed with AIDS in the United 
States. A larger number are infected with HIV, many of whom are not yet 
diagnosed. In the United States, African-Americans and Hispanic or Latino 
Americans are disproportionately infected with HIV. 

o Persons infected with HIV often develop a multisystem dysfunction, and 
those with AIDS typically have severe abnormalities in many organ systems. 
Persons infected with HIV with or without AIDS may develop significant 
metabolic abnormalities and alterations in body composition, which impact 
quality of life and longevity. Individuals co-infected with hepatitis C may 
follow a more virulent course to severe morbidity and/or death. Patients with 
HIV infection may also experience chronic diarrheal syndrome, AIDS 
enteropathy, for which no etiologic agents is identified other than HIV 
infection.   Development of HIV-related nephropathy may occur early in the 
course of the disease, with or without AIDS, and may progress to end-stage 
renal disease. In the period 1997-2001, AIDS nephropathy was the reported 
cause of ESRD in 1 percent of all incident ESRD patients.

Diseases of the Prostate:
o Although the available data show that prostate cancer has a higher 
prevalence in African-Americans, the racial disparities for nonmalignant 
diseases have never been accurately assessed. However, it is assumed that 
they follow a pattern similar to that of prostate cancer.

o In addition to racial disparities in disease prevalence, the disparities in 
types of therapy, effectiveness of therapy, and effectiveness of screening 
programs have not been studied or evaluated.

Gallbladder Disease:
o In the United States, more than 600,000 cholecystectomies are performed 
yearly to treat symptomatic gallstone disease with resulting costs 
approaching $10 billion.  The disease is more common in women and increases 
with age.  Information on ethnicity as related to gallstones has been limited 
by insufficient or inaccurate characterization of ethnicity.  Recent 
population based ultrasonographic studies have revealed substantial ethnic 
differences in risk of gallstones.  Risk is highest among American Indians 
followed by Hispanics in Chile, Mexican American women in the United States, 
and Polynesians.  

o Among women, risk of gallbladder disease is highest among American Indians, 
followed by Hispanics, non-Hispanic whites and non-Hispanic blacks.  

o Higher case fatality occurs among non-Hispanic blacks than non-Hispanic 
whites suggesting that blacks may have inadequate access to medical care for 
gallbladder disease. 
  
Peptic Ulcer Disease and H. Pylori:
o Peptic ulcer disease is a chronic gastrointestinal disease that affects 
over ten percent of the population in the United States.  It is estimated 
that more than 50% of peptic ulcer diseases is caused by H. Pylori infection 
and that H. Pylori is more prevalent among minority populations.  The 
prevalence of H. Pylori infection is reported to be about 62% in Mexican 
Americans and 53% in non-Hispanic blacks compared to 26% in non-Hispanic 
whites.

o H. Pylori infection increases the risk for stomach cancer, which is twice 
as high among non-Hispanic blacks as it is among non-Hispanic whites.  Native 
American and Mexican Americans are also at increased risk.  

Sickle Cell Disease:
o Sickle cell disease affects more than 70,000 Americans.  The disease 
exhibits the highest frequency in people of African descent.  In African 
Americans, one in 600 persons has the disease, and an additional one in 12 is 
a carrier for sickle cell trait. 

Scope:
The overall objective of this Program Announcement is to understand and 
mitigate health disparities in the development, diagnosis, and treatment of 
diseases of high priority to NIDDK, i.e., diabetes, obesity, nutrition-
related disorders, hepatitis C, gallbladder disease, H. Pylori infection, 
sickle cell disease, kidney diseases, and metabolic, gastrointestinal, 
hepatic, and renal complications from infection with HIV.  It is recognized 
that both biologic and non-biologic factors may be operating in these 
populations.
 
Approaches may include metabolic, genetic, clinical 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 some of the diseases.  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.

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

o Studies on the impact of medical services for the prevention and treatment 
of diabetes, obesity, nutrition-related disorders, hepatitis C, gallbladder 
disease, H. Pylori infection, sickle cell disease, kidney diseases, and 
complications from infection with HIV the in diverse racial/ethnic groups.

o Studies are needed to better understand racial and ethnic differences in 
the incidence and prevalence of these diseases and whether there are 
differences among sub-groups in the rates of progression.

o Studies to determine if there are disparities in the diagnosis of diabetes 
and pre-diabetes and the effect, if any, on onset of complications and their 
progression.

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 or development of obesity and risk of complications in different 
populations.  Such studies might determine, for example, whether some groups 
are at greater risk for type 2 diabetes from insulin resistance or from 
reduced beta-cell reserve; whether fat content and distribution differ among 
race-ethnic groups, and what metabolic or physiologic processes are 
responsible in the pathogenetic pathway leading to type 2 diabetes.

o Studies of pregnancy in mothers with pre-existing or gestational diabetes 
and risk for diabetes and obesity in children in minority populations and 
potential mechanisms for any increase in risk.  Studies of the role of the in 
utero environment on the subsequent development of pre-diabetes or diabetes. 
Studies are needed to assess whether abnormalities in the uterine environment 
contribute to ethnic/racial disparities in the incidence of type 2 diabetes, 
and, conversely, whether there are racial/ethnic differences in the response 
to a given in utero milieu. 

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 
populations.

o Studies to compare the contribution of glycemia versus other risk factors 
(e.g., smoking, dyslipidemia, body composition, blood pressure, markers of 
inflammation) 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 or behavioral factors, such as medical 
care, lifestyle, and socioeconomic status that may contribute to risk for 
development and progression of obesity or diabetes and its 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).  

o Studies of intervention to reduce or prevent weight gain in children or 
adults of minority populations.

o Studies of effects of medications or other therapies for prevention or 
treatment of type 2 diabetes, obesity or their complications in racial or 
ethnic minority populations, including children.

o Studies of the reasons for the racial and ethnic disparities in the 
incidence and prevalence rates of ESRD. 

o Studies of the basic mechanisms, and differential causes and progression of 
kidney disease to end-stage renal disease in racial and ethnic groups. 

o Studies to explore the mechanism for greater resistance to therapy and to 
find more effective regimens for the treatment of hepatitis C in African-
American and Hispanic-Americans.

o Studies of mechanisms for poorer survival after liver transplantation and 
methods to improve survival.

o Studies to explore severe metabolic abnormalities of AIDS or hepatitis C or 
AIDS nephropathy.

o Studies of racial disparities in prevalence of diseases of the prostate 
(especially non-malignant) and type and effectives of therapies.

o Studies to further explore ethnic differences in prevalence of gallbladder 
disease and disparities in health care access and utilization.  
Environmental, biological or genetic studies are needed to understand 
underlying mechanisms for ethnic difference in development of gallbladder 
disease.

o Studies to explore differences in H. Pylori infection in ethnic groups and 
the relationship ethnic differences in the development of stomach cancer in 
persons infected with H. Pylori.

o Studies to identify genetic modifiers to the phenotypic expression of 
sickle cell disease.  Studies to investigate possible new targets for 
therapeutics for sickle cell disease.  

MECHANISM(S) OF SUPPORT 

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 $275,000 direct costs for 
the two year period. For example, the applicant may request $100,000 in the 
first year and $175,000 in the second year.  The request should be tailored 
to the needs of the project.  Normally no more than $200,000 will be 
requested in a single year. 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 budgeting as 
well as the non-modular budgeting formats.  (see 
http://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 budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.    
  
ELIGIBLE INSTITUTIONS 

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 institutions/organizations
o Foreign institutions are not eligible to apply 
o Faith-based or community-based organizations 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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

WHERE TO SEND INQUIRIES 

We encourage your 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:

o Direct your questions about scientific/research issues to:

Myrlene Staten, M.D. 
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 6107
Bethesda, MD 20892-5460
Telephone:  (301) 402-7886
FAX:  (301) 480-3503
Email: ms808k@nih.gov 

Lawrence Agodoa, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 653
Bethesda, MD 20892-5460
Telephone:  (301) 594-5454
FAX:  (301) 594-9358
Email: la21j@nih.gov 

Marva Moxey-Mims, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 639
Bethesda, MD 20892-5460
Telephone:  (301) 451-5037 
FAX:  (301) 480-3510
Email: mm726k@nih.gov 

Frank Hamilton, M.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 669
Bethesda, MD 20892-5460
Telephone:  (301) 594-8877 
FAX:  (301) 480-8300
Email: fh14e@nih.gov 

o Direct your questions about financial or grants management matters to:

Kathleen J. Shino
Supervisory Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 708 
Bethesda, MD  20892-5456
Telephone:  (301) 594-8869 
FAX:  (301) 480-3504
E-mail: ks48e@nih.gov 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html 
in an interactive format.  For further assistance contact Grants Info, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

In addition, the PA title and number must be typed on line 2 of the face page 
of the application form and the YES box must be marked

SUPPLEMENTARY INSTRUCTIONS 

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 $275,000 for the two year period.

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.  Use the instructions for appendix detailed in the PHS 398 except that no 
more than 5 manuscripts, previously accepted for publication, may be 
included.  

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.  R21 applications deemed not to be responsive to this program 
announcement will be returned.

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

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular budget grant format.  The modular budget 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 http://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 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers 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 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

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 
http://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 unfunded version of an application 
already reviewed, but such application must include an Introduction 
addressing the previous critique.  

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

PEER REVIEW PROCESS

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

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

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 written critique
o Receive a second level review by the National Diabetes and Digestive and 
Kidney Diseases Advisory Council 

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 evaluate application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review 
group will address and consider each of the following criteria in assigning 
the application’s overall score, weighting them as appropriate for each 
application.

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  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 be advanced? What 
will be the effect of these studies on the concepts or methods that drive 
this field?

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

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

INVESTIGATOR: Is the investigator 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 (if any)?

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

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

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below). 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

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 Inclusion Criteria in the sections on 
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. 
http://grants.nih.gov/grants/policy/data_sharing  
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

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 of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

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). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.(NIH Policy for Data and Safety Monitoring, NIH Guide for Grants 
and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
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, 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.

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 - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are 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 RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy 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 
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 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 
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 (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The 
Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information”, 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as “covered entities”) must do so by April 14, 2003 (with the 
exception of small health plans which have an extra year to comply).  

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

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

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

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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
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Bethesda, Maryland 20892
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and Human Services (HHS)
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