CENTERS FOR INNOVATION IN MEMBRANE PROTEIN PRODUCTION
 
RELEASE DATE:  October 27, 2003

RFA Number:  RFA-RM-04-009 - (Reissued as RFA-RM-08-019)

(formerly RFA-GM-04-004, see NOT-OD-04-008)

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

THIS RFA IS DEVELOPED AS A ROADMAP INITIATIVE. ALL NIH INSTITUTES AND 
CENTERS PARTICIPATE IN ROADMAP INITIATIVES.

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.859
 
LETTER OF INTENT RECEIPT DATE:  February 5, 2004 
APPLICATION RECEIPT DATE:  March 11, 2004
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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 Supplemental Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

This Request for Applications (RFA) solicits proposals to establish 
Centers for Innovation in Membrane Protein Production.  The goals of 
these Centers will be to create enabling technologies and to focus on 
innovative, high-impact, and multidisciplinary approaches to sample 
preparation of structurally and functionally intact membrane proteins 
for structure determination.  The collaborative and coordinated effort 
made possible by multiple, interdisciplinary investigators associated 
with research Centers is required to accelerate technological advances 
in this important area.  The goal of the Centers, not possible with 
other funding mechanisms or previous program announcements, will be the 
multidisciplinary and non-hypothesis-driven technology development of 
innovative tools and methods for the expression, solubilization, 
stabilization, reconstitution, and purification of membrane proteins.  
The Centers will disseminate their results, methods, and materials in a 
timely manner.  They will also track state-of-the-art developments in 
membrane protein production and structure determination as guides in 
the selection of appropriate subprojects, cores, approaches, and 
targets.  It is expected that the activities of the Centers for 
Innovation in Membrane Protein Production will complement the 
activities of investigator-initiated research, as supported by the R01, 
R21, and P01 mechanisms, and the goals of the NIGMS Protein Structure 
Initiative research centers.  Because no single institution may have 
the variety of expertise required for membrane protein preparation and 
characterization, Centers involving multiple, cooperating institutions 
bringing together innovative combinations of scientific disciplines 
will be encouraged.
 
RESEARCH OBJECTIVES

Membrane proteins play a crucial role in many cellular and 
physiological processes.  They are essential mediators of material and 
information transfer between cells and their environment, between 
compartments within cells, and between compartments comprising the 
organ systems.  Functionally normal membrane proteins are vital to 
health, and specific defects are associated with many known disease 
states.  Membrane proteins are the targets of a large number of 
pharmacologically and toxicologically active substances and are 
responsible, in part, for their uptake, metabolism, and clearance.

The NIH Roadmap process for program initiative prioritization, 
established by the NIH Director, Dr. Elias Zerhouni 
(http://nihroadmap.nih.gov), has identified Structural Biology as a 
major area for additional near-term investment.  Determining the 
structures of membrane proteins is an intermediate- to long-term goal.  
An increase in the number of known membrane protein structures will 
contribute to an enhanced understanding of many basic phenomena 
underlying cellular functions essential to human health.  Improved 
membrane protein preparation using novel approaches is an important 
first step.

The goal of the Centers is the development of innovative, 
multidisciplinary methods that will yield structurally and functionally 
intact membrane proteins for subsequent structural studies.  Thus far, 
most membrane protein structures have been solved for proteins that can 
be obtained from naturally rich sources.  However, many of the proteins 
of greatest human physiological and pharmaceutical relevance are of 
relatively low abundance.  Although membrane proteins may be expressed 
in recombinant form, there is a need to develop more robust expression 
systems for membrane proteins.  For oligomeric membrane proteins, 
efficient co-expression of membrane protein subunits and assembly 
systems are required. 

Centers may focus on why certain detergents and/or lipids with novel 
phase properties are more successful in the solubilization of membrane 
proteins than others. Studies leading to the chemical synthesis of 
novel detergents and/or the development of non-detergent methods for 
solubilizing and stabilizing membrane proteins are encouraged.  Other 
research areas should include efficient methods to characterize the 
functional state of the expressed and purified membrane proteins as 
well as their lipid and detergent contents, state of aggregation, 
physical homogeneity, and sequence microheterogeneity.  Protein 
characterization may include tests of the suitability of purified 
proteins for structure determination, such as preliminary 
crystallization trials or NMR analyses, but these activities are not to 
be major activities funded by the Center grant awards.

The development of innovative, multidisciplinary, and even speculative, 
approaches to the fractionation and purification of membrane proteins 
is also highly encouraged.  Novel applications of genomic and proteomic 
approaches and screens that might complement or enhance traditional 
approaches such as centrifugation, partitioning, precipitation, 
chromatography, isoelectric focusing, and electrophoresis are 
requested.  Non-traditional approaches such as the use of protein 
and/or lipid chaperones, conformation-specific antibodies, covalent 
modification, stabilizing mutations, and structural scaffolds should be 
proposed to express, solubilize, and purify membrane proteins.

Although the application of the purified membrane protein samples is 
structure determination, the major focus of each Center should be 
development of innovative approaches for obtaining membrane proteins 
that are structurally and functionally intact.  It is expected that 
these Centers will contribute to the solution of many more membrane 
protein structures over the next five years through collaboration with 
researchers funded outside the scope of the Centers.  These 
contributions to knowledge of membrane protein structure and membrane-
protein association should feed back into an understanding of ways to 
improve expression, solubilization, stabilization, reconstitution, and 
purification.

A program announcement on the Structural Biology of Membrane Proteins 
has been in effect for several years (see: 
http://www.nigms.nih.gov/funding/pa/membrane.html).  This announcement 
includes research on protein production, crystallization, isotopic 
labeling, and the solution of membrane protein structures.  Thus far, 
most responsive projects have involved single or relatively small 
groups of researchers and standard approaches.  The Centers will 
provide opportunities for larger, organized, multidisciplinary and 
collaborative groups of researchers to attack these problems, and they 
are expected to use novel and high risk approaches for membrane protein 
preparation and to facilitate interactions with and among the smaller 
groups of researchers.  

The Protein Structure Initiative (PSI; see: 
http://www.nigms.nih.gov/psi/) seeks to accelerate the rate of protein 
structure solution.  Some of the PSI centers include limited efforts to 
determine membrane protein structures, and the PSI program 
announcements encourage support of technology development for high-
throughput approaches to membrane protein structure determination (see: 
http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-00-006.html).  
However, based on a workshop evaluating progress of the PSI research 
centers, protein production is one of the major rate limiting steps to 
structure determination, and this is especially true with respect to 
membrane proteins (see: 
http://www.nigms.nih.gov/news/reports/protein_production.html).  
Therefore, there is a need for a separate program initiative that 
focuses primarily on the coordinated development of innovative and 
high-risk methods for membrane protein preparation. 

MECHANISM OF SUPPORT
 
This RFA will use NIH P50 Specialized Center Grant award mechanism to 
promote multidisciplinary research focused on the goal of developing 
innovative methods for expressing, solubilizing, reconstituting, and 
purifying membrane proteins in a functional form suitable for structure 
determination and characterization.  Center Grants provide support for 
innovative subprojects and allow more flexibility to modify research 
goals when new opportunities arise.  

The applicant 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 by September 30, 2004. 

Groups of investigators interested in the subject area of this RFA, but 
wishing to mount a project of smaller scope, might find the P01 
mechanism more appropriate (see: 
http://grants.nih.gov/grants/guide/pa-files/PA-01-116.html.

Although not discouraged, 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. However, 
evidence of institutional commitment and support should be presented.

FUNDS AVAILABLE
 
The NIH intends to commit approximately $5.0 million in FY2004 to fund 
at least two new Center grants in response to this RFA. An applicant 
may request a project period of up to five years and a budget for total 
direct costs of up to $1.5 million for the first year.  Facilities and 
administrative (F & A) costs on subprojects are not included in this 
cap.  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 ICs 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 if your institution is domestic and has 
one 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  

The majority of the research should be done at domestic institutions, 
but a Center may include a foreign subproject.  Although NIH may not 
award a grant to an NIH component, an NIH component may be included as 
a subproject or a scientific collaboration associated with the Center.  
However, funds are not allocated to intramural NIH investigators and 
laboratories, unless under extremely rare and exceptional 
circumstances.  
 
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 his/her 
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

Center Structure:

Subprojects for Methods Development:  The principal funded research to 
be carried out by the Centers will be the technological development of 
innovative methods for the expression, over-expression, solubilization, 
stabilization, reconstitution, and purification of membrane proteins.  
This research should be set out as a series of specific, 
multidisciplinary subprojects, each focusing on different but 
complementary and novel approaches.  Additional goals of the Centers 
should be the dissemination of the methods developed and their 
availability to investigators outside the Center.  These subprojects 
should be headed by an appropriately qualified investigator, who may or 
may not be the overall Center director and principal investigator (PI).  
Not all subprojects need to begin in the first year.  Some may be 
phased-in as progress on the initial projects allows.  A variety of 
approaches to each problem should be presented.

Core Research Facilities:  The rationale for establishing a Center 
should be the common scientific objectives of the participants, not the 
support of a core facility.  However, a Center application may request 
support for scientifically justified facilities, including equipment 
and support personnel.  Plans should be presented for providing core 
access to all participants in the Center and for making unique Center 
facilities available to collaborating researchers outside of the Center 
participants.

Administrative Core:  A plan should be presented for the overall 
administration of the Center and for the prioritization, selection, 
deletion, and evaluation of subprojects, cores, methods, and 
approaches.  Plans for rapidly adjusting the Center priorities as 
projects succeed or fail should also be outlined.  Methods and criteria 
for flexibly evaluating, initiating, and replacing cores and 
subprojects should be described.  The decision making process for 
disseminating methods and results should be presented.  This 
dissemination should take the form of a database, website, or other 
appropriate information tools.  The PI should indicate how the methods 
and open-source software developed by the Center will be available to 
the research community.  A plan should be presented for citation of 
Center support, determining authorship, and resolving other 
acknowledgement and intellectual property (IP) issues that may arise 
among participants and collaborators.  The PI has responsibility for 
the overall operation of the Center.  Delegated areas of responsibility 
should be clearly indicated.  Plans for any internal or external 
advisory committees should be specified, but advisory committee members 
should not be identified or selected until after an award has been 
made.

Information Sharing:  It is expected that Center participants will 
publish their results in the usual ways.  In addition, Centers should 
include plans to establish databases or websites for the purpose of 
sharing information, such as experimental protocols, materials, 
software programs, and results, including negative data that are not 
generally publishable in great detail.  Plans for reducing positive 
data and outcomes to best practices should also be outlined. 

Annual Meeting:  All Center participants should meet on at least an 
annual basis.  The meetings may be held at the home institution of the 
Center’s principal investigator, at one of the other participating 
institutions, or at another location, such as in conjunction with a 
relevant scientific meeting, or in Bethesda.  Travel funds to support 
this activity should be requested in the budget.  NIH staff should be 
invited to participate in these meetings.  Other mechanisms should also 
be presented to assure regular communication and interaction between 
Center participants.

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:

John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Building 45, Room 2AS.13B, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0533 
FAX:  (301) 480-2004 
Email:  norvellj@nigms.nih.gov  

o Direct your questions about peer review issues to:

Helen R. Sunshine, Ph.D. 
Office of Scientific Review
National Institute of General Medical Sciences
Building 45, Room 3AN.12F, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-2881
FAX:  (301) 480-8506
Email:  sunshinh@nigms.nih.gov

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

Ms. Grace Olascoaga
Division of Extramural Activities
National Institute of General Medical Sciences
Building 45, Room 2AN.32E, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5520
FAX:  (301) 480-2554
Email:  olascoag@nigms.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:

John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Building 45, Room 2AS.13B, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0533 
FAX:  (301) 480-2004 
Email:  norvellj@nigms.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 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.

SUPPLEMENTARY INSTRUCTIONS: 

The Center should support an integrated, coordinated program, with 
various interdependent subprojects.  The subprojects and cores must be 
fully described and justified.  Collaborations and consortia are 
encouraged.  In such collaborations, the respective contributions 
should be well integrated into the design of the application.  The 
application should have a face page; abstract; key personnel listing; 
consolidated budget; subproject and core budgets; biographical 
sketches; institutional support, resources and facilities; project 
summary; subproject and core descriptions; plans for administrative 
management; plans for project management with annual milestones and 
evaluations; plans for sharing results and materials; plans for 
handling intellectual property issues; description of any consortium 
arrangements; and letters of collaboration.  The project summary 
section should define the overall scope and objectives of the Center.

The page limit for the research plan (including specific aims, 
background and significance, preliminary studies, and research design 
and methods) is increased to 60 pages total.

The budget should be no greater than $1.5 million direct costs for the 
first year, with annual cost-of-living increases in subsequent years.  
It should be fully justified and should include funds for attending the 
annual meeting.  

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 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.  While the investigator may 
still benefit from the previous review, the RFA application is not to 
state explicitly how.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIGMS.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.  Applications that are complete and responsive to the 
RFA will be evaluated for scientific and technical merit by an 
appropriate peer review group convened according to NIH procedures 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 appropriate 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.  
The goal of the P50 Centers for Innovation in Membrane Protein 
Production is to promote multidisciplinary and interdisciplinary 
approaches to develop innovative methods and technologies to express, 
solubilize, reconstitute, and purify membrane proteins.  In the written 
comments, reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
o Additional Review Criteria (see below)

The scientific review group will address and consider each of these 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application.  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 or hypothesis driven but is essential to move 
a field forward.  If the P50 Center grant application includes distinct 
subprojects and scientific cores, the scientific merit of each will be 
assessed, based on its merit, its potential contribution to the success 
of the overall project, and its interactions with other subprojects, 
the cores, collaborators, and the scientific community.  However, 
separate priority scores will not be assigned for subprojects and 
cores.  The overall priority score assigned to the Center proposal will 
reflect the reviewers’ enthusiasm for the Center as a whole, taking 
into account their levels of enthusiasm for only those projects and 
cores, which they recommend for funding.  Projects and cores which are 
seriously flawed and not recommended for inclusion in the Center will 
be specifically noted in the text of the summary statement.

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?  Are a variety of strategies 
presented?

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?  Are the approaches multidisciplinary and high impact?

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?  
Do the principal investigator and subproject investigators have the 
managerial experience and leadership skills required?  Is the principal 
investigator committed to the center, its goals, and projects?

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 and resources 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:

Interactions and Interdisciplinarity:  Degree to which the subprojects 
interact with each other and with the cores to create a Center, which 
is more than the sum of the parts.  Degree to which to the goal of 
promoting interdisciplinary interactions among scientists is achieved.

Plans for Evaluating and Prioritizing Subprojects and scientific cores:  
Adequacy of plans for selecting and evaluating a variety of subprojects 
and scientific cores for membrane protein preparation and purification, 
for tracking new ideas and developments, and for modifying, adding, or 
deleting subprojects and cores because of these new developments. 

Plans for Making Center Facilities Available:  Adequacy of plans to 
make unique Center facilities, results, materials, and methods 
available to collaborative researchers and to enhance collaborations.

Plans for the Overall Administration:  Adequacy of plans for any 
internal or external advisory committees, for annual and strategic 
planning meetings, for assuring communication, interaction, and synergy 
among Center participants and the scientific community, and for 
handling intellectual property issues.

Plans for Data Sharing:  Adequacy of plans for sharing of Center 
discoveries and data via databases, websites, distribution of software, 
and other means of dissemination beyond the usual publication of 
results.

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, 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.  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:  February 5, 2004 
Application Receipt Date:  March 11, 2004 
Peer Review Date:  June-August, 2004
Council Review:  September 2004
Earliest Anticipated Start Date:  September 30, 2004

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

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 

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.

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 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


H H S Department of Health
and Human Services

 
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