Release Date:  August 29, 2001

RFA:  RFA-AG-02-003

National Institute on Aging

Letter of Intent Receipt Date:  November 13, 2001
Application Receipt Date:       December 12, 2001



The National Institute on Aging invites research applications to expand 
knowledge on aging- and age-related aspects of prostate cancer in different 
populations at varying risk for this disease.  Prostate cancer is a major 
age-related malignancy.  Seventy-one percent of prostate cancer incidence and 
92% of prostate cancer deaths occur in the age group 65 years and older.  Older 
men of all race and ethnic backgrounds are at risk for prostate cancer, however, 
the burden of this malignancy varies according to age, race, and ethnicity.  
Among diverse male population groups in the United States, African Americans and 
Caucasians have the highest prostate cancer incidence and higher mortality 
rates.  By contrast, American males of Asian and Hispanic descent, and American 
Indians, and Alaska Natives have lower incidence and mortality rates than 
African Americans and Caucasians.  

Epidemiologic data describe these differences to a limited extent, but there is 
a dearth of information on why rates vary so dramatically in prostate cancer 
risk according to age, race, and ethnicity.  Factors accounting for disparities 
among the diverse population groups and the impact of this malignancy 
concomitant with aging are unknown.  There is a paucity of data available 
regarding age-related differences on the biologic properties and clinical 
aspects of prostate cancer among different race/ethnicity populations. 

The purpose of this RFA is to support research that will provide information 
leading to better prevention, diagnosis, prognosis, and treatment of prostate 
cancer in the age range in which prostate cancer most frequently occurs in the 
diverse population groups at risk (i.e., in men 65 years and older).  Proposals 
to address the issues indicated above may be focused on genetic and 
environmental risk factors, pre-malignant changes, tumorigenesis, detection of 
localized and advanced disease, prognostic indicators, disease progression, and 
response to treatment.  Studies to evaluate or refine the ability of existing 
diagnostic, screening, or follow-up methods of persons of different age, race, 
and ethnicity are also responsive to this RFA.  All proposed studies should 
address aging- or age-related factors.  Comparisons of individuals from two or 
more population groups are strongly encouraged, but not mandatory.


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 Request for Applications (RFA), 
Aging, Race, and Ethnicity in Prostate Cancer, is related to one or more of the 
priority areas.  Potential applicants may obtain a copy of "Healthy People 2010" 


Applications may be submitted by domestic and foreign for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of state and local governments, and eligible agencies of the 
Federal government. Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as principal investigators.


This RFA will use the National Institutes of Health (NIH) research project grant 
(R01) award mechanism.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.  Awards 
will be administered under NIH grants policy as stated in the NIH Grants 
Policy Statement.

This RFA is a one-time solicitation.  Future unsolicited competing continuation 
applications will compete with all investigator-initiated applications and be 
reviewed according to the customary peer review procedures.  The anticipated 
award date is July 2002.

Specific application instructions have been modified to reflect "MODULAR GRANT" 
and "JUST-IN-TIME" streamlining efforts that have been adopted by the NIH. 
Complete and detailed instructions and information on Modular Grant applications 
have been incorporated into the PHS 398 (rev. 5/2001). Additional information on 
Modular Grants can be found at


For FY 2002, $2,500,000 will be committed by NIA to fund applications submitted 
in response to this RFA.  A total of 5 to 7 meritorious applications will be 
awarded that are relevant to the NIA mission.  Although the financial plans of 
the Institute provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a sufficient number 
of applications of outstanding scientific and technical merit.  The RFA will not 
be reissued. 

Direct costs will be awarded in modules of $25,000 up to a maximum of $350,000, 
less any overlap or other necessary administrative adjustments. Facilities and 
Administrative costs will be awarded at the negotiated rate.



The National Institute on Aging (NIA) identified prostate cancer as a research 
priority in its 1997 Program Announcement, “Aging, Race, and Ethnicity in 
Prostate Cancer” (PA-97-019), NIH Guide to Grants and Contracts, Volume 25, 
Number 44.  The PA encouraged the extramural research community to take 
advantage of recently acquired scientific knowledge and expertise developed in 
biology, gerontology, oncology, urology, and other disciplines and professions 
and apply these resources to aging-relevant research questions on prostate 
cancer for men of different races and minority backgrounds.  

The impetus for the earlier program announcement and this RFA is based on the 
magnitude of prostate cancer in older men as a significant public health 
problem.  This is dramatically indicated by the National Cancer Institute (NCI) 
Surveillance, Epidemiology, and End Results (SEER) program data, 1994-98.  The 
magnitude of the prostate cancer problem increases with advancing age.  Prostate 
cancer has the highest age-adjusted incidence rates of any malignancy in men 65 
years and older, 1457.7 (black males) and 932.2 (white males) per 100,000 
population.  Age-adjusted incidence rates per 100,000 population for black and 
white males under age 65 years, by contrast, are 96.4 and 49.4 per 100,000 
population, respectively.  Peak age-specific incidence rates per 100,000 
population for this tumor in African Americans are in the five-year age groups 
70-74 years (1747.9) and 75-79 (1562.0) years.  Caucasian Americans incidence 
rates in these same age groups are 70-74 years (1084.0) and 75-79 (1056.8) 
years.  The highest rates of prostate cancer mortality per 100,000 population 
are in black males aged 80-84 (922.4) and 85+ (1323.8) years.  For white males 
the mortality rates, while also the highest in the 80-84 (403.6) and 85+ (732.8) 
age groups, are roughly half those for black males. [1]

Contributing to the prominence of the prostate cancer problem in older men are 
two age-relevant demographic phenomena -- extended life expectancy and an 
overall increase in the U.S. population.  Male life expectancy at birth for 
males has increased from 46.3 years at the beginning of the 20th century to 73 
years (2000).[2]  The U.S. population is made up of a greater proportion of 
older men than in previous decades.  Over 10% of the current total male 
population is 65 years and older.  By 2030 the percentage is projected to 
increase to over 18%.  In numbers, this represents an increase from over 14 
million males 65 years and older in the U.S. population (2000) to a projected 31 
million men in this age group by 2030. [3].  

Research Goal/Scope

The goal of this RFA is to stimulate research that will provide information 
leading to better diagnosis, prognosis, and treatment of prostate cancer in the 
age range in which prostate cancer most frequently occurs in the diverse 
race/ethnicity population groups at risk such as African Americans, Caucasians, 
Asians, Hispanics, American Indians, and Alaska Natives.  These may include 
studies targeting men of advancing age (among whom prostate cancer rates are 
highest, but on whom relatively little prostate cancer research has been 
conducted) and comparative age studies of older men and younger men afflicted 
with this malignancy.

The RFA encourages extension and application of current scientific knowledge and 
expertise in prostate cancer to age-relevant topics and development of new 
approaches at the aging/cancer research interface.  The studies solicited by 
this RFA may include exploratory approaches such as primary data collection; 
secondary analyses of existing data; development or validation of diagnostic 
methods in different age and ethnic groups; and feasibility testing of 
recruitment, screening, or patient assessment protocols in different age or 
ethnic groups. Applicants are encouraged to utilize pertinent existing resources 
where applicable, such as data or subjects from epidemiologic studies or 
clinical trials, and prostate and other tissue banks.

Targeted areas of research for this RFA solicitation are listed below.  While 
the research categories cover a large variety of scientific areas relevant to 
aging, race, and/or ethnicity, investigators may suggest related issues for 
consideration if they meet the two RFA criteria stipulated in the SPECIAL 
REQUIREMENTS SECTION of this document. 

o Studies on prostate tumor biology, host response, and tumor progression
-- Age-related differences in tumor initiation, progression, and /or development 
of metastases.
-- Variations in tumor cellular and molecular properties in biopsy or surgical 
specimens related to age, race, and ethnicity and their relationship to tumor 
progression and metastases.
-- Examination of the effects of age-related changes in tumor properties (as 
distinguished from those of age-related changes in host responses) on tumor 
initiation, progression, and metastasis. 
-- Variation in responses of tumor cells from patients of different ages to 
chemotherapeutic agents or radiation.

o Studies (epidemiologic or biologic investigations) on prostate cancer risk 
factors and carcinogenesis 
-- Effects of age-related physiologic or pathophysiologic changes (e.g., benign 
prostatic hypertrophy, prostatic intraepithelial neoplasia (PIN), changes in 
reproductive hormone levels) on risk for prostate cancer.
-- Studies on the malignant potential of genetic changes or biological damage 
from oxidative processes. 
-- Effects of known and putative genetic and exogenous factors (e.g., alcohol 
consumption, smoking), and their interactions, on risk for prostate cancer 
incidence at different ages in different populations. Studies of these risk and 
protective factors within ethnic groups at highest risk of the disease are 
particularly encouraged. 
-- Age-related cellular and molecular changes in prostate tissue obtained from 
biopsy, surgical, or autopsy specimens regarding their potential contribution to 
pre-malignant changes or tumorigenesis. 

o Studies (epidemiologic or clinical investigations) on prognosis, diagnosis and 
-- Effects of age as it interacts with race and/or ethnicity or of aging alone 
on sensitivity, specificity, and prognostic value of screening (e.g., PSA) and 
diagnostic techniques (e.g., sextant biopsy) and scales (e.g., Gleason score) 
and their predictive value for treatment responsiveness. This includes testing 
current values of prognostic indicators (e.g., PSA) to assess age-specificity 
for achieving efficient early detection of clinically significant cancer in 
older men (i.e., 70 years and older).  
-- Effects of patient characteristics (e.g., age-related comorbid conditions, 
age-related physiologic changes) on tumor progression and response to therapy at 
different ages, including adverse effects. 
-- Relationship of age, and age-related conditions and physiologic changes, to 
efficacy and adverse effects of different prostate cancer treatments. 
-- Methods to distinguish age-related differences in patients with and without 
clinically significant prostate cancer  (e.g., indolence versus aggressive tumor 
behavior in the context of the aged host).   

o Surveillance studies focused on using population-based cancer registries  
-- Organize and conduct prospective cohort studies of men diagnosed with 
prostate cancer to include pre-diagnostic information (biopsies, PIN, and 
pretreatment PSA) and how these data may vary according to age and race and 
ethnicity or aging alone.-- Evaluate risk for recurrence and metastasis 
after treatment
-- Develop tissue bank resources in association with cancer registration

o Follow-up tissue studies of patients on clinical trial prostate cancer 
protocols to ascertain characteristics of older prostate cancer patients as 
compared to younger patients and how they vary according to race and/or 
ethnicity on selected outcomes after treatment.

o Studies of prostate cancer of patients across the age spectrum who are of 
different race and ethnic groups with striking differences in incidence rates 
according to residence in the same or different geographic areas to identify 
more specifically the etiologic factors and to study their relationships with 
biomarkers of exposure.


A distinctive feature of this research solicitation is the requirement that 
proposals test hypotheses about aging, including potential differences among 
populations that are at disparate risks for prostate cancer. To be responsive to 
this RFA, an application must meet the following criteria: 

1.  The proposed study should address the relationship of age- or aging-related 
factors to prostate cancer risk focusing on one or more of the following -- 
biologic properties, detection, prognosis, diagnostic accuracy, or treatment 
efficacy. Examples of types of studies that are encouraged include, but are not 
limited to: comparisons of persons of different ages, studies of the effects of 
known age-related changes on prostate cancer risk or outcomes, or studies of 
factors affecting the rate of progression with age of premalignant changes or 
prostate cancer risk factors.  Studies that do not address age- or aging-related 
factors will not be considered responsive.  Comparisons of individuals from two 
or more population groups are strongly encouraged, but not mandatory.

2.  The research must be focused on human prostate cancer.  In vitro studies of 
human cells or tissues, and xenograft studies of human prostate cancer or normal 
human prostate tissue in laboratory animals may be proposed.


It is the policy of the NIH that members of minority groups and their sub-
populations must be included in all NIH-supported biomedical and behavioral 
research projects involving human subjects, unless a clear and compelling 
rationale and justification are 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 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 
August 2, 2000 
(; a complete 
copy of the updated Guidelines are available at  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to 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) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.


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 site.


NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  This policy announcement is found 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 RFA 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.


Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel and 
participating institutions, and the number and title of the RFA in response to 
which the application may be submitted. Although a letter of intent is not 
required, is not binding, and does not enter into the review of a subsequent 
application, the information that it contains allows IC staff to estimate the 
potential review workload and to plan the review.

The letter of intent is to be sent to the program staff listed under INQUIRIES 
by the letter of intent receipt date listed in the heading of this RFA.


The PHS 398 research grant application instructions and forms (rev. 5/2001) at are to be used in 
applying for these grants. This version of the PHS 398 is available in an 
interactive, searchable PDF format. Although applicants are strongly encouraged 
to begin using the 5/2001 revision of the PHS 398 as soon as possible, the NIH 
will continue to accept applications prepared using the 4/1998 revision until 
January 9, 2002.  Beginning January 10, 2002, however, the NIH will return 
applications that are not submitted on the 5/2001 version.  For further 
assistance contact GrantsInfo, Telephone 301/710-0267, Email:


The modular grant concept establishes specific modules in which direct costs may 
be requested as well as a maximum level for requested budgets. Only limited 
budgetary information is required under this approach. The just-in-time concept 
allows applicants to submit certain information only when there is a possibility 
for an award. It is anticipated that these changes will reduce the 
administrative burden for the applicants, reviewers and NIH staff.  The research 
grant application form PHS 398 (rev. 5/2001) at is to be used in 
applying for these grants, with modular budget instructions beginning on page 13 
of the application instructions. Applicants are permitted, however, to use the 
4/1998 revision of the PHS 398 for scheduled application receipt dates until 
January 9, 2002. If you are preparing an application using the 4/1998 version, 
please refer to the step-by-step instructions for Modular Grants available at

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA number 
on the label.  Failure to use this label could result in delayed processing of 
the application such that it may not reach the review committee in time for 
review.  In addition, the RFA title and number must be typed on line 2 of the 
face page of the application form and the YES box must be marked.  The RFA label 
is also available at:

Submit a signed, original of the application, including the Checklist, and three 
signed photocopies of the application in one package to: 

6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, send two additional copies of the application to:

Mary Nekola, Ph.D.
Chief, Scientific Review
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Room 2C212
Bethesda, MD  20892-9205

It is important to send these copies at the same time as the original and three 
copies are sent to the Center for Scientific Review. These copies are used to 
identify conflicts and to help ensure the appropriate and timely review of the 

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will be 
returned to the applicant without review.


Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIA. Incomplete and/or nonresponsive applications will be 
returned to the applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
NIA in accordance with the review criteria stated below. As part of the initial 
merit review, a process may be used by the initial review group in which all 
applications receive a written critique and undergo a process in which only 
those applications deemed to have the highest scientific merit, generally the 
top half of the applications under review, will be discussed, assigned a 
priority score, and receive a second level review by the National Advisory 
Council on Aging.

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.  Each of these criteria 
will be addressed and considered in assigning the overall score, weighting them 
as appropriate for each application.  Note that 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.

1.  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?

2.  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?

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:  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)?

5.  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?

o The adequacy of plans to include minorities and their subgroups as appropriate 
for the scientific goals of the research. Plans for the recruitment and 
retention of subjects will also be evaluated.

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o 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.

The personnel category will be reviewed for appropriate staffing based on the 
requested percent effort.  The direct costs budget request will be reviewed for 
consistency with the proposed methods and specific aims.  Any budgetary 
adjustments recommended by the reviewers will be in $25,000 modules.  The 
duration of support will be reviewed to determine if it is appropriate to ensure 
successful completion of the requested scope of the project.


Letter of Intent Receipt Date:  November 13, 2001
Application Receipt Date:       December 12, 2001
Date of Initial Review:         March 2002
Review by Advisory Council:     May 2002
Anticipated Award Date:         July 2002


The following will be considered in making funding decisions:  Quality of the 
proposed project as determined by peer review, availability of funds, and 
program priority.


Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Rosemary Yancik, Ph.D.
Geriatrics Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3E 327 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-5278
FAX:  (301) 402-1784
Email:  ry3e@NIH.GOV

Direct inquiries regarding fiscal matters to:

Jean Richelsen
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672


This program is described in the Catalog of Federal Domestic Assistance No. 
93.866.  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 and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 
92.  This program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.

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, 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.


1.  Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg LX, Edwards BK 
(eds), SEER Cancer Statistics Review, 1973-1998, National Cancer Institute, NIH 
Pub. No. 00-2789, Bethesda, MD, 2000

2.  Health, United States, 1999 Health and Aging Chart Book, DHHS Publication 
Number (PHS) 99 1232-1, Health Status, pp 30-40

3.  Day JC, Population Projections of the United States by Age, Sex, and 
Hispanic Origin:  1995-2050, U.S. Bureau of the Census, Current Population 
Reports, P25-1130, U.S. Government Printing Office, Washington, DC, 1996

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