CLINICAL RESEARCH IN PERIPHERAL ARTERIAL DISEASE

RELEASE DATE:  October 10, 2002
						
RFA:  HL-03-003								
 
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov)

LETTER OF INTENT RECEIPT DATE: January 24, 2003

APPLICATION RECEIPT DATE: February 26, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) 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 Citation

PURPOSE OF THIS RFA
 
This program aims to develop improved therapeutic and preventive approaches for 
atherosclerotic arterial diseases of the peripheral vasculature through 
integrated, multi-disciplinary clinical research projects.  Key objectives 
include elucidating biological mechanisms related to the initiation, 
progression, and outcomes of disease; enhancing early detection by developing 
improved biomarkers, imaging approaches, and other relevant biomedical 
technologies; and developing novel therapeutic and preventive strategies. 

RESEARCH OBJECTIVES

With the advent of new technologies and scientific concepts, opportunities now 
exist for translation of our knowledge of peripheral arterial disease (PAD)into 
better clinical management.  Emphasis in this RFA will be placed on multi-
disciplinary clinical research designed to improve understanding of underlying 
mechanisms and translate this understanding into improved strategies for 
diagnosis, therapy and prevention of PAD.

Background: The Public Health Dimensions of PAD

Pathologies of the peripheral vasculature are responsible for a wide variety of 
clinical conditions associated with considerable mortality and particularly high 
morbidity.  For example, in 1999 there were 2 million physician office visits 
and 1.3 million hospitalizations in which peripheral vascular disease was cited 
as either a primary or secondary diagnosis.  Of the peripheral vascular 
diseases, PAD is the most prevalent (8-12 million cases in the U.S.).  The 
considerable economic damage attributable to PAD stems from lost productivity 
and high health care costs.  Leg pain, impaired mobility, and even amputation 
are frequent consequences of PAD, with serious effects on functional capacity 
and quality of life.  PAD may not be symptomatic at early stages, and even after 
symptoms occur they may not be perceived as needing medical attention. 

The risks and clinical course of PAD are affected by age, ethnicity, and the 
presence of other medical conditions. PAD is often considered to be a disease of 
the elderly, with more than 20% of people over 75 years affected; the number of 
cases is expected to increase as the population ages.  However, attention has 
recently been drawn to higher-than-expected rates of PAD in younger individuals, 
and to the generally severe outcome in this age group.  Similarly, PAD risk is 
elevated in individuals with diabetes, and as the rates of type 2 diabetes rise 
secondary to the increasing prevalence of obesity, PAD rates also will likely 
increase.  Regarding gender, little is known of whether, or how, women differ 
from men regarding susceptibility to and progression of PAD.

In the United States, minority populations suffer an undue burden of PAD.  
Notably, the rate of amputations performed in the U.S. is much higher in the 
African-American and Native American populations than in Caucasians, 
particularly among those with diabetes.  Genetic and other factors influencing 
the development and progression of PAD and response to treatment among different 
racial/ethnic groups need to be better understood. 

Of deep concern is the degree to which PAD presages future serious events, 
particularly among middle-aged patients.  In the Framingham study cohort, of the 
35-64 year olds who were diagnosed with intermittent claudication, 35% of men 
and 23% of women were dead within 8 years.

Research needs in PAD

Research is needed that will focus specifically on knowledge gaps in PAD, as 
opposed to atherosclerotic disease in general (also see Exclusions, below).  
Important barriers to satisfactory prevention, diagnosis, and treatment of PAD 
include: insufficient understanding of the underlying pathophysiology and 
pathobiology; difficulty of predicting individual susceptibility;  initial 
diagnosis at typically late stages of disease; and limited range of effective 
therapeutic options.

Pathobiology, pathophysiology, and individual susceptibility

Atherosclerosis accounts for most peripheral arterial occlusive disease.  
Although many of the risk factors for atherosclerotic coronary artery disease 
(such as smoking, hyperlipidemia, hypertension, hyperglycemia, obesity, and 
hyperhomocysteinemia) have been identified as risk factors for PAD, strong 
evidence is lacking that risk factor modification is effective in halting 
progression or improving outcomes.  A better understanding is needed regarding 
the clinical and pathophysiologic responses to risk factor interventions.  

Genomic and proteomic approaches may be useful in identifying individuals at 
particular risk of PAD, independent of coronary artery disease risk, and in 
predicting the likelihood of benefit from interventions.  Such approaches could 
provide key information for identifying those individuals who should be directed 
towards early detection programs.

A better understanding is needed of the relationships among blood vessel 
function, hemodynamics, organ damage, and functional status of the patient.  For 
example, many patients with ischemic limbs have experienced years of reduced 
blood flow to those limbs.  Defects at the metabolic and structural levels may 
not be corrected by improving perfusion.  Conversely, exercise often improves 
limb or organ function out of proportion to measurable changes in hemodynamics; 
this may be due to underlying metabolic changes that are poorly understood.  It 
also is known that both exercise and arterial occlusion are potent stimuli to 
angiogenesis despite diverse metabolic effects.  The specific metabolic pathways 
that are affected by PAD are not well understood at present, but ultimately 
metabolic changes may prove to be more useful than hemodynamic measurements as 
determinants of functional outcome.  These observations suggest that a more 
thorough understanding is needed of biochemistry, muscle biology, and exercise 
physiology in PAD. 

The basis of the observed differences in risk factors and risk relationships for 
small vs. large vessel PAD needs to be clarified in terms of underlying 
pathophysiology.   Also, the acute and chronic changes that occur in the 
microcirculation following large vessel obstruction are not well understood.  
For example, the effect of ischemia on vascular bed function has not been 
clearly defined.  Once a vascular bed has been damaged, this injured vasculature 
and any newly-developed collateral vasculature may have properties that differ 
from those of the original bed.

Earlier diagnosis and better therapies

A majority of patients with significant atherosclerotic obstruction of the lower 
extremities (ankle/brachial artery indices (ABI) <0.9) do not seek clinical care 
until the disease reaches critical stages.  There is a need to study the 
progression of PAD in individuals who have low ABI values either with or without 
coronary artery disease.  Multifactorial interventions need to be evaluated 
(including lipid-lowering agents, anti-platelet therapy, anti-hypertensive 
therapy, exercise, and control of blood glucose) to determine how to attain the 
maximum benefit for these patients.  It also may be important to investigate the 
effects of treatment on insulin requirements.  Studies are needed that focus on 
the use of specific drugs or classes of drugs (e.g., statins, anti-platelet 
agents, and inhibitors of the renin-angiotensin system) in subsets of PAD 
patients.  

Another area to consider is the role of stenting, with or without other 
modalities, in non-coronary arteries.  It is not known whether drug-eluting 
stents are helpful in reducing restenosis or native vessel disease progression 
in peripheral arterial occlusive disease. 

New techniques for functional imaging that provide quantitative and objective 
measures of impairment are critical to future vascular studies.  Optimal imaging 
of the peripheral vessels may require approaches that differ from those 
developed for the coronary circulation.  Imaging could also be used to assess 
the impact of systemic changes induced by drug treatment or other therapeutic 
modalities. 

Novel treatment options might include revascularization of damaged peripheral 
vessels through cell-based therapies.  Gene therapy for PAD, another potentially 
fruitful approach, currently is directed towards inducing angiogenesis or 
arteriogenesis; however, other dimensions also merit exploration.  

Summary of Research Priorities

The following describes areas of particularly high interest (also see 
Exclusions, below), which include but are not limited to: 

O   Studies of interventions such as exercise, pharmacotherapy or percutaneous 
revascularization in PAD.

o   Studies of hemodynamic influences, regional microcirculation, and other 
factors in determining the distribution, severity, progression, and regression 
of PAD;

o   Evaluation of diagnostic techniques, including new markers and imaging 
approaches, having improved precision for detection and characterization of PAD;

o   Studies of the interactions among the coagulation system, inflammatory 
pathways, lipid pathways, and glucose homeostasis in the etiology, progression,  
and treatment of PAD;

o   Cell-based and gene transfer approaches for stimulating revascularization;

o   Tissue engineering approaches for treatment; and 

o   Studies involving stem cell plasticity relevant to PAD. 

Multi-disciplinary research is encouraged.  Relevant scientific disciplines and 
areas of expertise include but are not limited to: internal medicine and 
surgery; diagnostic imaging and biomedical engineering; biochemistry; vascular 
biology; physiology; pathology; genetics; immunology; genomics; proteomics; 
biostatistics and clinical trials management; pharmacology; nutrition; and 
exercise science.

Although increasing, the small number of vascular surgeons engaged in active 
research has long been of concern, and is considered a hindrance to progress 
with PAD. There are similarly few clinicians in internal medicine with research 
interests in PAD per se.  Individuals in these professions are strongly 
encouraged to apply or be involved in the planning and execution of these 
programs.

MECHANISM OF SUPPORT
 
This RFA will use the NIH R01 (Investigator-initiated research project grant) 
award mechanism.  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 30, 2003.

This RFA uses just-in-time concepts.  It also uses the modular 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 format.  Otherwise follow the instructions for 
non-modular research grant applications.

FUNDS AVAILABLE
 
The NHLBI intends to commit approximately $5 million in total costs in FY 2003 
to fund 5 to 7 new grants in response to this RFA.  An applicant may request a 
project period of up to 5 years and a budget for total costs of up to $1 million 
per year. 

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 NHLBI 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.  At 
this time, it is not known if this RFA will be reissued.

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
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 under-represented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply 
for NIH programs.   
 
SPECIAL REQUIREMENTS

Clinical Research

In order for a project to be considered clinical for the purposes of 
responsiveness to this RFA, the research must be patient-oriented.  To be 
responsive, clinical investigations must include studies of patients with 
peripheral arterial disease.  Normal healthy subjects may be included, but only 
in combination with studies involving patients.  In studies involving the use of 
human specimens, the investigators must have direct interaction with the patient 
and relate the research results to the patient status or outcome for this to be 
considered a clinical project. 

Applicants are encouraged to pursue patient-oriented research on topics related 
to health disparities and the translation of this research to clinical practice 
for affected minority populations.  Clinical research projects are required to 
include women, minorities and children in the study population unless such 
inclusion can be demonstrated to be inappropriate.

Human biomedical studies of etiology, pathogenesis, prevention, diagnostic 
approaches, and treatment are responsive.  However, clinical research projects 
focused on large epidemiologic studies will be considered unresponsive to this 
RFA.  Clinical studies and trials undertaken in the context of this RFA should 
emphasize endpoints composed of symptom relief, functional improvement, and/or 
anatomic changes.  Studies should be relatively modest in size so that they can 
be conducted or coordinated by a single program or small consortium.

Clinical research projects will be subject to the standard NHLBI policies and 
procedures regarding human subjects monitoring.

Exclusions

Applications proposing programs that are not hypothesis-based and do not focus 
on clinical research will be considered non-responsive to the RFA.

Certain types of investigations, although potentially of scientific interest, 
will not be appropriate for support by this program.  Investigators wishing to 
develop proposals related to excluded categories are strongly encouraged to 
contact the NHLBI (see Inquiries, below) for information about other 
opportunities.   

Examples of excluded research are: 

o   projects with a primary focus of prospective or descriptive epidemiology; 

o   phase III clinical trials that cannot be completed, including analysis, 
within 5 years;
	
o   projects that do not include studies in humans;

o   projects with primary focus on the coronary circulation, cerebral 
vasculature, pulmonary vasculature, lymphatic system, or venous system; 

o   projects with primary focus on thromboembolic and other coagulation 
disorders; 

o   projects with primary focus on abdominal aortic aneurysm or stroke; and

o   projects having a primary focus on research resource development.

Grantees' Meetings 

Upon initiation of the program, the NHLBI will sponsor annual meetings to 
encourage exchange of information among investigators who participate in this 
program.  In their budgets, applicants should include funds for annual one-day 
grantees' meetings, most likely in Bethesda, Maryland.  Applicants should also 
include a statement in their applications indicating their willingness to 
participate in these meetings. The first such meeting likely will take place 
within 3 months of award. 

General Clinical Research Center (GCRC)

Applicants from institutions that have a GCRC funded by the NIH National Center 
for Research Resources may wish to identify the GCRC as a resource for 
conducting the proposed research.  If so, a letter of agreement from either the 
GCRC program director or principal investigator should be included with the 
application.

Additional Considerations

All grant applications submitted in response to this RFA should include sample 
size and statistical power calculations appropriate to the proposed study 
design.  In addition, applicants proposing development of research resources are 
encouraged to describe a plan to share such resources with other researchers.  
This could include appropriate information technology (such as DNA/protein 
microarray databases) or shipment of tissues. Please note that applications 
having a primary focus on research resource development will be considered non-
responsive. 

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:

Diane Reid, M.D.
Division of Heart and Vascular Diseases 
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Suite 9044, MSC 7956
Bethesda, MD  20892-7940
Telephone:  (301) 435-0515
Fax:  (301) 480-1336
Email:  ReidD@nhlbi.nih.gov

o Direct your questions about peer review issues to:

Anne Clark, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD  20892-7924
Telephone:  (301) 435-0270
FAX:  (301) 480-0730
Email:  ClarkA@nhlbi.nih.gov

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

Edward McGeehan
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Suite 7044, MSC 7926
Bethesda, MD  20892-7926
Telephone:  (301) 435-0148
FAX:  (301) 480-3310
Email:  McGeehaE@nhlbi.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 NHLBI 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 Dr. Anne Clark at the address 
listed under WHERE TO SEND INQUIRES.

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 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/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the Checklist, and three signed photocopies, in one 
package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and five 
collated sets of appendix material must be sent to Dr. Anne Clark at the address 
listed under WHERE TO SEND INQUIRES. 

Please note that applications delivered by individuals are no longer accepted; 
all applications must either come via courier delivery or via the US Postal 
Service (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html)

APPLICATION PROCESSING: 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.

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.  The CSR 
will not accept any application that is essentially the same as one already 
reviewed. This does not preclude the submission of substantial revisions of 
applications already reviewed, but such applications must include an 
Introduction addressing the previous critique.

Principal investigators should not send supplementary material without first 
contacting the Scientific Review Administrator (SRA).  The SRA will be 
identified in the letter sent to you indicating that your application has been 
received.  If you have not received such a letter within three weeks after 
submitting the application, contact Dr. Anne Clark at the address listed under 
WHERE TO SEND INQUIRIES.

PEER REVIEW PROCESS  

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI.  Incomplete applications will be returned to the 
applicant without further consideration.  And, if the application is not 
responsive to the RFA, CSR 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 
the NHLBI in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will:

o Receive a written critique

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 second level review by the National Heart, Lung, and Blood 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 discuss the following aspects of 
your application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals: 

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

Each project will be evaluated with respect to the following criteria:

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

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

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

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

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

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

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

o INCLUSION:  The adequacy of plans to include subjects from both genders, all 
racial and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the section 
on Federal Citations, below)

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

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

o OTHER REVIEW CRITERIA: 

The safety and data monitoring plan will be evaluated for adequacy (also see 
Monitoring Plan and Data Safety and Monitoring Board, below).

RECEIPT AND REVIEW SCHEDULE 	

Letter of Intent Receipt Date:       January 24, 2003
Application Receipt Date:            February 26, 2003
Peer Review Date:                    June/July, 2003
Council Review:                      September 4-5, 2003
Earliest Anticipated Start Date:     September 30, 2003

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 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for assessment 
of patient eligibility and status, rigorous data management, quality assurance, 
and auditing procedures.  In addition, it is NIH policy that all clinical trials 
require data and safety monitoring, with the method and degree of monitoring 
being commensurate with the risks (NIH Policy for Data Safety and Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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 AMENDMENT "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://grants.nih.gov/grants/stem_cells.htm 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 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.

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.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance No. 93.837, and is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review.  

Awards are made under authorization of Sections 301 and 405 of the Public Health 
Service Act as amended (42 USC 241 and 284) and administered under NIH grants 
policies described at http://grants.nih.gov/grants/policy/policy.htm and under 
Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

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.

Return to Volume Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.