PATHOGENESIS AND TREATMENT OF LYMPHEDEMA AND LYMPHATIC DISEASES

RELEASE DATE:  March 5, 2004

PA NUMBER: PA-04-071  

This funding opportunity has been replaced by PA-07-165, which now uses the electronic SF424 (R&R) 
application for February 5, 2007 submission dates and beyond.

(see addendum NOT-HL-04-111)

EXPIRATION DATE:  December 31, 2006, unless reissued.

Department of Health and Human Services (DHHS)

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

COMPONENTS OF PARTICIPATING ORGANIZATION: 
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov/)
National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
 (http://www.nih.gov/niams/)
National Cancer Institute (NCI)
 (http://www.nci.nih.gov/)
National Center for Complementary and Alternative Medicine (NCCAM)
 (http://www.nccam.nih.gov/)
National Institute on Biomedical Imaging and Bioengineering (NIBIB)
 (http://www.nibib1.nih.gov/)
National Institute of Nursing Research (NINR)
 (http://www.ninr.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):
93.213, 93.286, 93.333, 93.396, 93.837, 93.839, 93.846, 93.862

THIS PA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS PA 

The National Heart, Lung, and Blood Institute (NHLBI), National Institute of 
Child Health and Human Development (NICHD), National Institute of Arthritis 
and Musculoskeletal and Skin Diseases (NIAMS), National Cancer Institute 
(NCI), National Institute of Nursing Research (NINR), National Center for 
Complementary and Alternative Medicine (NCCAM), and National Institute on 
Biomedical Imaging and Bioengineering (NIBIB) invite qualified researchers to 
submit applications for research project grants to investigate the 
pathogenesis and new treatments for primary and secondary lymphedema.  The 
purpose of this program announcement is to stimulate research on the biology 
of the lymphatic system, to characterize at the molecular, cellular, tissue, 
organ, and intact organism levels, the pathophysiologic mechanisms that cause 
the disease, to develop new methods for quantitating and imaging lymph flow, 
to discover new therapeutic interventions, and to determine the safety, 
efficacy and mechanisms of action of complementary and alternative therapies.  
The scope of this research includes developmental biology and genetics of the 
lymphatic system to identify and characterize genes important for its 
organization and regulation.  Such knowledge will help to improve early 
diagnosis of affected individuals, the choice and timing of treatment, and 
genetic counseling.  Research is also needed on the pathophysiology of the 
disorders of skin and subcutaneous tissue secondary to chronic lymphedema, 
and lymphedema which results from cancers and cancer treatment, with an 
ultimate goal to develop more targeted and effective therapies.

RESEARCH OBJECTIVES

The lymphatic system comprises an important secondary circulatory system, 
returning interstitial fluid back to the venous circulation. Prior to this 
function, lymphatic vessels also regulate accumulation and turnover of 
interstitial fluid. When the mechanisms involved with this regulation become 
unbalanced, lymphedema results. There are two major types of lymphedema: 
primary (congenital) and secondary (caused by tissue injury, scarring, lymph 
node removal, or infection). For primary lymphedema, there is an early onset 
form (Milroy's disease) which is relatively rare and presents at birth. A 
more common type (Meige's disease) develops during puberty, representing 
approximately 80 percent of all cases. A third form, lymphedema tarda, occurs 
after the age of 35. Lymphedema frequently presents with one leg being more 
swollen than the other, which is not only disfiguring, but can lead to a 
severe infection (cellulitis), and diseases of the skin and subcutaneous 
tissues.  Primary lymphedema is inherited in an autosomal dominant fashion, 
with variable expressivity and penetrance, and with women affected almost 
three-fold more often than men.  The complexity of lymphatic development and 
function is likely to be regulated by a variety of unidentified genes, which 
result in the phenotype secondary to mutations in those genes.  Gene defects 
have been mapped in several families, with a recent study showing that a form 
of primary lymphedema involves a genetic missense mutation located on 
chromosome 5 for the receptor for vascular endothelial growth factor-C. This 
genetic lesion may implicate specific tyrosine kinase receptors as causative 
in certain types of lymphedema. However, the exact mechanisms which 
contribute to primary lymphedema remain unknown. 

The incidence of primary lymphedema has been estimated to be between 1/6000 
to 1/300 live births.  Thus, it could be a rare disease, or a more common 
disease which is underrecognized. On the other hand, there are 3-5 million 
people affected with secondary lymphedema in the United States, and according 
to the World Health Organization as many as 170 million world-wide. The 
secondary type of lymphedema develops after tissue injury, especially after 
cancer surgery, radiation therapy,  trauma to the lymphatic system and 
lymphangitis, inflammation or infection (e.g. filariasis) that interrupts 
normal lymphatic pathway function. 

Although lymphedema has been recognized for over a century, understanding its 
causes has received limited attention. The etiology of the disease is 
believed to be complex, involving defective fluid and solute transport across 
lymphatic vessels, insufficient propulsion of lymph within lymphatic vessels, 
and developmental defects unique to the lymphatic system. Further, therapy 
also has lagged, despite the prevalence of the disease, and little relief is 
gained from current interventions. One important factor responsible for the 
lack of study and treatment of lymphedemas is the paucity of unique animal 
models, including transgenic and knockout models, compared to other diseases. 

In view of the limited attention currently given to the biology of the 
lymphatic system, and the treatment of lymphedema, the NHLBI, NICHD, NIAMS, 
NCI, NINR, NIBIB, and NCCAM are interested in approaches that will identify 
the developmental, molecular, and cellular defects that contribute to 
lymphedema as well as the development of effective therapeutic interventions 
to treat both primary and secondary lymphedemas. These include: insufficiency 
of lymphatic circulatory function; lymphatic vascular valvular 
insufficiencies; complex congenital vascular proliferative diseases of the 
lymphatic vasculature, including but not limited to, so-called lymphangioma, 
cystic hygroma, lymphangiosarcoma, lymphangio-leiomyomatosis; and 
developmental disorders of the lymphatic system, e.g. lymphangiectasia, 
chylous reflux and complex vascular malformations, such as Klippel-Trenauny 
Syndrome.

Examples of some research topics are listed below to illustrate the 
objectives of this program announcement. It is not required that all or any 
of these ideas be included; investigators are encouraged to submit 
applications that are relevant to the goals of this program announcement.

1.  Comparative studies of gene expression in lymphedematous and normal 
tissues, using techniques such as laser capture microdissection and high 
density microarrays to identify molecular targets.

2.  Studies on the phenotypic and genotypic differences of lymphatic vascular 
cells, compared to arterial and venous vascular cells.

3.  Elucidation of the process of lymphangiogenesis, including the growth 
factors, cytokines, and matrix molecules associated with the formation of 
functional lymphatic vessels.  A potential role of trophism to lymph nodes, 
and the effect of reimplantation of nodal tissue on lymphedema.

4.  Development of a biophysical model(s) for interstitial fluid exchange 
across the lymphatic wall, and the role of the lymphatic matrix in the 
development of lymphedema. Characterization of the physical and biological 
mechanisms in the propulsion of lymph within lymphatic vessels.

5.  The creation of animal models to confirm the identification of putative 
genes contributing to lymphedema, and the development of animal models to 
assess new and complementary or alternative treatments.

6.  The development of methods to image and quantitate lymph flow to provide 
useful endpoints for clinical evaluations.

7.  Approaches to explain the asymmetry between more and less affected limbs 
in an individual with primary lymphedema, when the genetics and environment 
appear to be uniform. Also, the developmental or hormonal basis for onset 
that occurs during puberty.

8.  Studies on the developmental biology and developmental genetics of the 
lymphatic system, i.e., the identification and characterization of genes 
important in the organization and regulation of the development of the 
lymphatic system.

9.  Studies on diseases of skin and subcutaneous tissue that result from 
chronic lymphedema.

10.  New methods to prevent or treat lymphedema or lessen its impact on 
patients.

11. Development of biobehavioral markers to measure the relationship between 
health-related quality of life (HRQOL) and lymphedema, including markers to 
measure the impact of therapeutic interventions.

12.  A national patient registry and tissue bank.

To foster data sharing in addition to presentations and publications, 
investigators should consider how to make experimental results available to 
other scientists for data mining, and how to make archived data interoperable 
with commercially available software.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH individual research project grant (R01) award 
mechanism. As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project, which is not to exceed a 
period of 5 years.  This PA also uses just-in-time concepts, and the modular 
budgeting as well as the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.

ELIGIBLE INSTITUTIONS 

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

For clinical studies, a Data and Safety Monitoring Plan (e.g. creation of a 
Data Safety and Monitoring Board, refer to Federal Citation at the end of the 
document); documented ability to enroll a specified number of patients; semi-
annual reports; special expertise or facilities; review between Phase I and 
Phase II; and coordination among investigators (e.g. annual meetings), etc., 
must be included.

Describe any requirements for sharing research data, if appropriate. Note 
that all applications that list direct costs greater than $500,000 in any 
year of the proposed research, must have a data sharing plan.

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Henry Chang, M.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7950
Bethesda, MD 20892-7950
Telephone: (301) 435-0067
FAX: (301) 480-1060
Email: changh@nih.gov
 
Stephen S. Goldman, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7956
Bethesda, MD 20892-7956
Telephone: (301) 435-0565
FAX: (301) 480-2849
Email: goldmans@nih.gov

A. Tyl Hewitt, Ph.D.
Chief, Developmental Biology, Genetics and Teratology Branch
National Institute of Child Health and Human Development
Building 6100, Room 4B01E
6100 Executive Blvd. MSC 7510
Bethesda MD 20892-7510
Telephone: (301) 496-5541
FAX: (301) 480-0303
Email: th119v@nih.gov

Alan N. Moshell, M.D.
Skin Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 45, Room 5AS25L
45 Center Drive, MSC 6500
Bethesda, MD 20892-6500
Telephone: (301) 594-5017
FAX: (301) 480-4543
Email: alan_n_moshell@nih.gov

Suresh Mohla, Ph.D. 
Chief, Tumor Biology & Metastasis Branch 
Division of Cancer Biology 
National Cancer Institute 
6130 Executive Blvd, EPN 5038 
Rockville, MD 20892 
Telephone:  301 435 1878 
FAX:  301 480-0864
Email: mohlas@mail.nih.gov

Martha L. Hare, Ph.D., R.N
National Institute of Nursing Research
6701 Democracy Boulevard
One Democracy Plaza, Room 710
Bethesda, MD  20892-4870 (Courier: 20817)
Phone: 301-451-3874
Fax: 301-480-8260
Email: martha.hare@nih.gov

Barbara C. Sorkin, Ph.D.
Division of Extramural Research and Training
National Center for Complementary and Alternative Medicine
6707 Democracy Blvd., Suite 401
Bethesda, MD 20892-5475
Telephone:  (301) 496-8004
FAX:  (301) 480-3621
Email: sorkinb@mail.nih.gov

Alan C. McLaughlin, Ph.D.
Division of Applied Science and Technology
National Institute of Biomedical Imaging and Bioengineering
6707 Democracy Blvd, Suite 200
Bethesda, MD 20892-5477
Telephone: (301) 496-9321
FAX: (301) 480-4973
Email: mclaugal@mail.nih.gov

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

Suzanne White
Grants Operations Branch
National Heart, Lung, and Blood Institute
Rockledge 2, Room 7160
Bethesda, MD 20892-7926
Telephone: (301) 435-0171
FAX: (301) 480-3310
Email: WhiteSa@nhlbi.nih.gov

Annette Hanopole
Grants Management Branch
National Institute of Child Health and Human Development
Bldg. 6100, Room 8A17F
6100 Executive Blvd. MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6975
FAX: (301) 402-0915
Email: hanopola@mail.nih.gov

Melinda Nelson
Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 45, Room 5AS49F
45 Center Drive, MSC 6500
Bethesda, MD 20892-6500
Telephone: (301) 594-3535
FAX: (301) 480-5450
Email: melinda_nelson@nih.gov

Mr. Bill Wells
Grants Administration Branch
National Cancer Institute
Executive Plaza South 243
Bethesda, MD  20892-7150
Telephone:  (301) 496-8796
FAX:  (301) 496-8601
Email:  wellsw@mail.nih.gov

Teresa Marquette
Grants Management Branch
National Institute of Nursing Research
6701 Democracy Boulevard
One Democracy Plaza, Room 710
Bethesda, MD  20892-4870 (Courier: 20817)
Phone: 301-594-2177
Fax: 301-402-4502
Email: tm275a@nih.gov

Marc Milton Pitts, M.B.A. 
Sr. Grants Management Specialist 
National Center for Complementary and Alternative Medicine 
National Institutes of Health 
6707 Democracy Blvd. 
Democracy II, Suite 401 
Bethesda, MD  20892 
Telephone:  301-594-9095
FAX:  301-480-1552
Email:  pittsm@mail.nih.gov

Ms Nancy Curling
Grants Management Office
National Institute of Biomedical Imaging and Bioengineering
6707 Democracy Blvd, Suite 900
Bethesda, MD 20892-5469
Telephone: (301) 496-9315
FAX: (301) 480-4974
Email: curlingn@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 DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html 
in an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

The title and number of this program announcement must be type on line 2 of 
the face page of the application form and the YES box must be checked.

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

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: 
Applications requesting up to $250,000 per year in direct costs must be 
submitted in a modular budget grant format.  The modular budget grant format 
simplifies the preparation of the budget in these applications by limiting 
the level of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for the 
PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm. 

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.  
Applicants requesting more than $500,000 must carry out the following steps:

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

2)   Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,

3)   Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

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

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

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

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

PEER REVIEW PROCESS

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

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

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review 
group will address and consider each of the following criteria in assigning 
the application's overall score, weighting them as appropriate for each 
application.

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and 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?  

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

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

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

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data 

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

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

AWARD CRITERIA

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

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

REQUIRED FEDERAL CITATIONS 

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

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy, 
effectiveness and comparative trials (phase III). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.  (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing 
Investigators should seek guidance from their institutions, on issues related 
to institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule. Reviewers will 
consider the data sharing plan but will not factor the plan into the 
determination of the scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:   It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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

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

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

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

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

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

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.