DEVELOPING INTERVENTIONS FOR MULTIPLE MORBIDITIES
 
RELEASE DATE:  August 27, 2004
 
RFA Number:  RFA-AG-05-007 
 
EXPIRATION DATE:  January 14, 2005

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATIONS: 
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATIONS:  
National Institute on Aging (NIA)
 (http://www.nia.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.866   
 
LETTER OF INTENT RECEIPT DATE:  December 14, 2004
APPLICATION RECEIPT DATE:  January 13, 2005   

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The National Institute on Aging (NIA) requests R34 and R21 applications 
exploring potential interventions to decreasing morbidity, mortality, 
and disability associated with multiple, co-occurring diseases in 
elderly patients.  This initiative supports (1) planning projects for 
clinical trials to design and test interventions supported by current 
epidemiologic and clinical evidence (R34 applications), and (2) 
exploratory studies to establish a scientific basis for future 
interventions (R21 applications).  The focus of both types of 
activities should be on improving health outcomes related to 
interactions of multiple co-occurring diseases or conditions in elderly 
patients.  

The coexistence of multiple chronic conditions (“multiple morbidity”) 
is more common among older patients than younger ones and confers a 
special burden in its compound effects on overall health status, 
functional ability, and quality of life.  This initiative builds on our 
understanding of the epidemiology and pathophysiology of co-occurring 
disease processes to decrease the complex and interacting morbidities 
and disabilities associated with multiple coexisting chronic medical 
conditions.  Its goal is, ultimately, to improve overall health status 
of elders with coexisting diseases and to decrease the associated 
disabilities through evidence-based medical care that takes into 
account their complex interactions. 
 
RESEARCH OBJECTIVES
 
BACKGROUND

The co-occurrence of diseases and/or disease processes (“multiple 
morbidity” or “multimorbidity”) is a highly prevalent problem in 
clinical medicine, particularly among older patients.  Multiple medical 
diagnoses have been reported as frequently as 78% among people age 80 
years and older, a marked increase from the 10% baseline observed for 
children and teenagers (ages 0-19 years) in the same general practice 
population (1).   In a recent population-based survey of men and women 
55 -84 years of age, 65% of participants reported 1-3 diagnoses of 
common medical problems ( e.g., heart disease, hypertension, diabetes, 
arthritis, cancer, stroke, pulmonary disease) and 19% reported 4 or 
more coexisting diagnoses.  (2).   Gender-specific age differences in 
the number of diagnoses were statistically significant (p<0.01):  women 
ages 65-84 reported more numerous diagnoses than their younger 
counterparts and than men of the same ages.  Similarly, 81% of 
community dwelling women ages 65 years and older screened for 
participation in the Women’s Health and Aging Study reported two or 
more chronic medical problems, and 18% reported five or more (3); 
although health was considered excellent or good by 71% of this 
population, only 5% reported having none of the 14 chronic conditions 
assessed in the study.

An increasing body of research demonstrates that the coexistence of 
multiple diseases increases the likelihood of disability.  Several 
studies demonstrate an increased risk of impaired mobility associated 
with increasing number of diagnoses (1, 4-6), while others show 
increased difficulty with activities of daily living (1, 7, 8).  
Related research suggests that combinations of certain diseases may 
have a synergistic impact on functional status, both in general 
activities of daily life and in specific activities or functions (3).  
The association of multimorbidity with increasing age and functional 
compromise suggests that, as the general population ages, the public 
health burden of co-occurring diseases will increase significantly.

Diseases that are common in elders, such as hypertension and arthritis, 
may occur together by chance alone.  However, the impact of co-
occurrence on functional status is often greater than the “sum” of the 
impacts of the individual chronic diseases.  For example, Fried et al. 
show that the combination of arthritis and hypertension are associated 
with a much greater increase in risk of disability in higher function 
and self care (OR 7.5) than either condition alone (arthritis OR 2.4, 
hypertension OR 0.9) (3).  The co-occurrence of disease processes more 
frequently than predicted by chance alone suggests common risk factors 
and/or overlapping pathophysiology.  Recognition and exploration of 
“common pathways” of these co-occurring conditions offers the potential 
for improved medical management as well as for targeted interventions 
to decrease the synergistic interactions of impairment and disability.

KNOWEDGE TO BE ACHIEVED

Despite the implications of multiple morbidity for geriatric care, 
relatively little attention has been given to the complex clinical 
interactions and interrelationships of the co-occurring chronic 
diseases.  This initiative supports preliminary research and planning 
activities that will provide a basis for clinical studies addressing 
the management of health and/or functional problems related to multiple 
morbidity.  Ultimately, this research and its subsequent intervention 
studies should contribute to the development of evidence-based 
treatment strategies for patients with multiple medical problems, 
demonstrating efficacy and safety in the presence of co-occurring 
diseases, and/or improving functional outcomes in elderly patients with 
multiple morbidities.

The preliminary studies supported through this initiative should 
provide the knowledge required to give a scientifically sound basis for 
clinical intervention studies targeting co-occurring conditions.  In 
this RFA, the term “condition” refers to diseases, disabilities, or 
physiologic impairments.  The knowledge to be achieved includes but is 
not limited to the following:

1. Identifying important health issues related to the coexistence in 
older persons of two or more specific conditions for which the optimal 
choice from currently available interventions is unknown, or for which 
new treatments might improve outcomes.  Examples are issues related to:
 
o  a combination of conditions in which one or more condition 
aggravates one or more of the other conditions, 

o  a combination of conditions for which currently available treatments 
for one condition have adverse effects on one or more of the others,

o  a combination of co-existing conditions that have overlapping 
etiologies or risk factors; 

o  a combination of conditions that synergistically increases risk for 
other conditions or adverse outcomes, 
 
o  a combination of conditions in which one or more condition confounds 
the diagnosis or clinical evaluation of one or more other conditions; 
or 

o   interactions of treatments for more than one condition produce 
adverse effects or outcomes.

2. For each important health issue - identifying one or more possible 
interventions that might be tested in a clinical trial or trials to 
address this health issue.  Possible types of interventions include:

o  single therapies, 

o  combinations of therapies, or 

o  treatment algorithms for individualizing therapy. 

3. For each important health issue and possible intervention - 
identifying potential outcomes that might be measured in a trial or 
trials to address this health issue.  Outcomes to be considered 
include:

o  effects of the intervention on each of the selected coexisting 
conditions, 

o  outcomes such as morbidity, mortality, disability, and/or 

o  the rate of progression of the study conditions and their associated 
functional limitations.  

4.  For each important health issue, possible intervention, and set of 
potential outcome measures to:

o  critically examine the “State-of-the-Science” regarding the 
combination of conditions;

o  determine whether the “State-of-the-Science” is adequate to support 
a trial of the intervention under consideration; and

o  if the “state-of-the-Science is adequate, design an appropriate 
clinical trial.  

Relevant considerations include but are not limited to(a) Do 
epidemiologic, pathophysiologic, and/or clinical data provide a 
sufficient rationale for the trial and indicate its feasibility?  (b) 
Given the prevalence of combinations of conditions in the older 
population and current patterns of “usual care,” is the trial under 
consideration practicable? (c) Are established methods and criteria for 
diagnosing or assessing the conditions under study, and for grading 
their severity, adequate for a clinical trial of the intervention under 
consideration?  (d) Are existing outcome assessment tools appropriate 
for use in participants with the proposed conditions?  If not, can 
existing tools be adapted to meet the needs of the study, or is the 
development of new assessment instruments required? (e) Are current 
statistical approaches suitable for exploring the interactions of 
multiple morbidities within the context of the prospective study?  Are 
innovative approaches needed to address specific questions in the 
proposed prospective clinical trial?

REFERENCES

1.  Van den Akker M, Buntinx F, Metsemakers JFM, et al.  Multimorbidity 
in general practice:  Prevalence, incidence, and determinants of co-
occurring chronic and recurrent diseases.  J Clin Epidemiol 1998; 51(5) 
367-375.
2.  Foley D, Ancoli-Israel S, Britz P, Walsh J.  Sleep disturbances and 
chronic disease in older adults:  Results of the 2003 National Sleep 
Foundation Sleep in America Survey.  (In press).
3.  Fried LP, Bandeen-Roche K, Kasper JD, et al.  Association of 
Comorbidity with disability in older women: The Women’s Health and 
Aging Study.  J Clin Epidemiol 1999; 52(1):27-37.
4.  Guralnik JM,  LaCroix AZ, Abbott RD, et al.  Maintaining mobility 
in late life:  Demographic characteristics and chronic conditions.  Am 
J Epidemiol 1993; 137:845-857.
5.  Ettinger WH, Davis MA, Neuhaus JM, et al.  Long-term physical 
functioning in persons with knee osteoarthritis from NHANES-I:  Effects 
of comorbid medical conditions.  J Clin Epidemiol 1994; 47:809-815.
6.  Campbell AJ, Busby WJ, Robertson MC, et al.  Disease, impairment, 
disability, and social handicap:  A community-based study of people 
aged 70 years and older.  Disabil Rehabil 1994; 16:72-79.
7.  Guralnik JM, LaCroix AZ, Everett DF, et al.  Aging in the Eighties:  
The Prevalence of Comorbidity and its Association with Disability.  
Advanced Data from Vital and Health Statistics (No. 170), 1989; 
National Center for Health Statistics, Hyattsville, MD.
8.  Mor V, Murphy J, Masterson-Allen S, et al.  Risk of functional 
decline among well elders.  J Clin Epidemiol 1989; 42:895-904.

MECHANISM OF SUPPORT  

This RFA will use both the NIH (R21) Exploratory/Developmental Research 
Grant and the NIH (R34) Clinical Trial Planning Grant award mechanisms.  
As an applicant you will be solely responsible for planning, directing, 
and executing the proposed project.  This RFA is a one-time 
solicitation.  Future unsolicited, competing-continuation applications 
based on this project will compete with all investigator-initiated 
applications and will be reviewed according to the customary peer 
review procedures. The anticipated award date is September 15, 2005.  
Applications that are not funded in the competition described in this 
RFA may be resubmitted as NEW investigator-initiated applications using 
the standard receipt dates for NEW applications described in the 
instructions to the PHS 398 application.  

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting format (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   This 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.  

Depending on the degree to which available data address the KNOWLEDGE 
TO BE ACHIEVED for a specific health issue and possible intervention, 
applicants may choose to apply for either the R21 or the R34 awards.

Exploratory/developmental research grants (R21)

Exploratory/developmental research grants may be proposed when 
preliminary information suggests that a health problem related to 
specific coexisting conditions might be addressed by a clinical trial, 
but there are insufficient data to support the rationale for such a 
trial, to evaluate its feasibility, or to plan it appropriately.  Such 
applications should identify the crucial gaps in necessary data, 
describe how the data could be obtained, and explain how they would be 
used in regard to a possible trial.  

Examples of needed studies and data that could be obtained in such 
exploratory studies include but are not limited to(a) epidemiologic, 
pathophysiologic, or clinical data to evaluate the impact of the 
clinical problem to be addressed, and/or the potential effects of 
interventions under consideration for a trial; (b) the development and 
validation of new diagnostic methods and criteria for the conditions, 
and for grading their severity, that are appropriate for the type of 
intervention study being considered; (c) the development and validation 
of new outcome assessment tools needed for the type of trial under 
consideration; and/or (d) the development of new statistical approaches 
needed to analyze interactions of multiple morbidities within and 
treatment effects in the type of trial under consideration.  

Exploratory/developmental research grant applications use the NIH R21 
mechanism as described in the program announcement PA-03-107:  NIH 
Exploratory/Developmental Research Grant Award (R21).  This program 
announcement is available online at 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html .  This 
mechanism allows a project period of up to two years and a combined 
budget (both years) up to $275,000 direct costs. No more than $200,000 
direct costs may be requested in a single year.  

Clinical Trial Planning grants (R34)

Planning grants for clinical trials may be proposed when current data 
provide strong support for the importance of the health problem to be 
addressed, the likelihood of efficacy of the intervention to be tested, 
the ability to assess conditions and outcomes appropriately, and the 
feasibility of conducting a trial.  

Applicants for planning grants may request funds for activities such as 
(a) preparing a detailed protocol and a Manual of Procedures; (b)  
analyzing existing data needed to refine the study design and protocols 
(e.g., power calculations, dosage or intensity of intervention, budget 
estimates); (c) conducting preliminary studies to guide selection of, 
and/or refine, study procedures and instruments, to estimate recruitment 
and retention potential, and to plan collection and analysis of 
biological specimens; and/or (d) providing travel expenses for 
individuals from multiple sites to planning meetings for the project.

Planning grant applications use the NIH R34 mechanism as in the program 
announcement PA-04-008:  NIH Clinical Trial Planning Grant (R34) 
Program.  This program announcement is available online at 
http://grants.nih.gov/grants/guide/pa-files/PA-04-008.html.  This 
mechanism allows a project period of one year and a budget for direct 
costs up to $100,000.   However, because of the additional complexities 
of studying multiple coexisting conditions, responses to this RFA may 
request direct costs up to $150,000.  

FUNDS AVAILABLE
 
The NIA intends to commit approximately $1,000,000 in FY 2005 to fund 3 
to 5 new awards in response to this RFA. For clinical trial planning 
grants (R34 mechanism), an applicant may request a project period of one 
year and a budget for direct costs of up to $150,000. For 
exploratory/developmental studies (R21 mechanism), an applicant may 
request a project period of up to two years and a budget for direct 
costs of up to $275,000 for the total project period, not to exceed 
$200,000 in any one year.  NIH no longer counts consortium F&A costs as 
a direct cost when determining if an applicant is in compliance with a 
direct cost limitation on a solicited application. 
See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html 
for further details.) Because the nature and scope of the proposed 
research will vary from application to application, it is anticipated 
that the size and duration of each award will also vary. Although the 
financial plans of the NIA provide support for this program, awards 
pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications.  
 
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 or foreign institutions/organizations
o Faith-based or community-based organizations.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

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

SPECIAL REQUIREMENTS

All applications should include travel expenses for the Principal 
Investigator to attend a 1-2 day annual meeting of awardees in 
Bethesda, MD, in Year 01 of the proposal budget. 

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Susan G. Nayfield, M.D., M.Sc.
Chief, Geriatrics Branch
Geriatrics and Clinical Gerontology Program
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Avenue
Bethesda, MD  20892-9205
Telephone:  (301) 496-6761
FAX:  (301) 402-1784
Email:  nayfiels@mail.nih.gov 

o Direct your questions about peer review issues to:

Michael Micklin, Ph.D.
Chief
Risk, Prevention, & Health Behavior Integrated Review Group
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Rm. 3136 MSC 7759
Bethesda, MD 20892 (20817 for overnight delivery)
Tel: 301-435-1258
FAX: 301-594-6363
E-mail: MicklinM@mail.nih.gov

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

Ms. Cynthia Riddick
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Suite 2N212
7201 Wisconsin Avenue
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  riddickc@nia.nih.gov
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Susan G. Nayfield, M.D., M.Sc.
Chief, Geriatrics Branch
Geriatrics and Clinical Gerontology Program
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Avenue
Bethesda, MD  20892-9205
Telephone:  (301) 496-6761
FAX:  (301) 402-1784
Email:  nayfiels@mail.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 D&B number can be obtained by calling (866) 
705-5711 or through the web site at http://www.dunandbradstreet.com/. 
The D&B number should be entered on line 11 of the face page of the PHS 
398 form. The PHS 398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an 
interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov. 
  
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs 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 
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.

USING THE RFA LABEL: 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: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
 
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 received on or before 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. 

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

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by NIA. Incomplete applications will not be 
reviewed. 
 
If the application is not responsive to the RFA, NIH staff may contact 
the applicant to determine whether to return the application to the 
applicant or submit it for review in competition with unsolicited 
applications at the next appropriate NIH review cycle.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by CSR in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

o 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 and assigned a priority score
o Receive a written critique
o 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 evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of 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:

o  Are the preliminary research projects or research planning 
activities consistent with the overall goals and specific aims of the 
RFA?

o  Will theses preliminary projects or activities support the design 
and implementation of an intervention study that addresses the medical 
management and associated medical and functional outcomes of co-
occurring diseases and/or disease proceses in older adults?

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).
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH: The adequacy of plans to 
include subjects from both genders, and all racial and ethnic groups 
(and subgroups) as appropriate for the scientific goals of the 
research.  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 

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

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: December 14, 2004
Application Receipt Date: January 13, 2005
Peer Review Date: June 2005
Council Review: September 2005
Earliest Anticipated Start Date: September 15, 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on 
Humane Care and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), 
as mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the 
USDA Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

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.

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.

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 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.

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

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

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

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA 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.

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NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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