HEPATITIS C: NATURAL HISTORY, PATHOGENESIS, THERAPY AND PREVENTION
RELEASE DATE: January 6, 2003 (see amendment NOT-DK-03-003)
RFA: DK-03-011
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov/)
National Cancer Institute (NCI)
(http://www.nci.nih.gov/)
National Heart, Lung, and Blood Institute (NHLBI)
(http://www.nhlbi.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
(http://www.niaaa.nih.gov/)
National Institute of Allergy and Infectious Diseases (NIAID)
(http://www.niaid.nih.gov/)
National Institute on Drug Abuse (NIDA)
(http://www.nida.nih.gov/)
LETTER OF INTENT RECEIPT DATE: March 11, 2003
APPLICATION RECEIPT DATE: April 15, 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 Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Specific instructions for R21 applications
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
National Cancer Institute (NCI), National Heart, Lung, and Blood Institute
(NHLBI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National
Institute of Allergy and Infectious Diseases (NIAID), and National Institute
on Drug Abuse (NIDA), invite grant applications for both basic and clinical
research in the areas of pathogenesis, natural history, therapy and
prevention of hepatitis C.
According to the National Health and Nutrition Examination Survey (NHANES) of
1988 1994, 3.9 million Americans were infected with hepatitis C, and of this
group, 2.7 million are estimated to have chronic infection. These estimates
likely under represent the true prevalence of HCV infection since NHANES was
a population-based household survey that excluded several groups with a
substantially increased prevalence of infection, such as persons who are
incarcerated, homeless, or institutionalized due to disability or mental
illness.
HCV is the most common blood-borne infection in the United States. HCV
transmission occurs primarily through exposure to infected blood.
Transmission risk factors include injection drug use, blood transfusion prior
to 1992, solid organ transplantation from infected donors, unsafe medical
practices, occupational exposure to infected blood, birth to an infected
mother, multiple heterosexual partners, and high-risk sexual practices. High
HCV seroprevalence rates (from 15 to 50 percent) have been observed in
specific subpopulations, such as the homeless, incarcerated persons, veterans
being followed at Veterans Affairs Medical Centers, and hemophiliacs, with
the highest rates (70 percent to 90 percent) reported in injection drug
users. In the general population, persons aged 40 to 59 years have the
highest prevalence of HCV infection, and in this age group, the prevalence is
highest in African-Americans (6.1 percent). Because of the high rate of
persistent infection long-term complications of chronic HCV infection are
projected to increase in the next 15 years.
Acute hepatitis C leads to chronic infection in approximately 75 percent of
cases. Age at the time of infection appears to be an important contributing
factor, spontaneous remission occurring more frequently in younger infected
individuals. Chronic hepatitis C is often asymptomatic and can be mild; but
in 20 percent of patients, the chronic infection leads to progressive liver
disease and ultimately cirrhosis and end stage-liver disease. These
conditions increase the risk of developing hepatocellular carcinoma (HCC).
There is little evidence that the risk of progression of liver disease is
affected significantly by virologic factors, including viral levels in the
serum, viral genotype, and quasispecies diversity. However, many host factors
have been found to increase this risk, including older age, male gender, and
an immune suppressed state, such as HIV co-infection. Environmental factors
that may complicate or worsen the course of chronic hepatitis C are alcohol,
iron overload, obesity, nonalcoholic fatty liver disease, schistosomal co-
infection, hepatotoxic medications, and possibly environmental contaminants.
The incidence of HCV-related liver cancer is continuing to rise in the United
States and worldwide, in part because of the increasing numbers of persons
who have been chronically infected for decades, the presence of comorbid
factors, and the longer survival of persons with advanced liver disease due
to improved management of complications. Although significant advances have
been made in the development of treatments for chronic hepatitis C, their
efficacy is not universal, and outcome of treatment is considerably affected
by viral and host factors. In optimally selected patients, the best current
therapies are effective in 40 to 50 percent of cases infected with viral
genotype 1 and in 70 to 80 percent of those infected with genotype 2 and 3.
Thus, the focus of the RFA is to elucidate the mechanism(s) responsible for
the acute and chronic injury caused by hepatitis C, define the factors that
determine the course and long-term outcome of chronic infection, including a
search for markers of fibrosis progression, and establish the basis for
resistance to the current therapeutic regimens followed by focused efforts to
improve the response rate with better and less toxic drugs. Since the most
effective way to prevent the liver disease caused by hepatitis C is through
the development of a preventive vaccine, this RFA also supports the
submission of applications that aim at generating a vaccine for hepatitis C.
RESEARCH OBJECTIVES
A recent NIH Consensus Development Conference entitled "the Management of
Hepatitis C: 2002"(http://consensus.nih.gov/cons/116/116cdc_intro.htm)
summarized the current knowledge about hepatitis C and made recommendations
regarding management and therapy. The Conference also provided key
recommendations of areas for future research studies on the epidemiology,
natural history, pathogenesis treatment and prevention of acute and chronic
HCV infection and its sequelae, in all affected populations.
Research Areas of Focus for this RFA
1. Characterization of the mechanisms of viral replication, chronicity of
infection, and resistance to host-determined antiviral factors as well as
administered antiviral agents:
Definition of the viral replication cycle from entry though production of new
virions, including definition of key viral functions, analysis of structure-
function relationships of viral enzymes/proteins, host-cell interactions and
mechanisms both in vitro and in vivo.
Identification of the molecular mechanism(s)and predictor(s) of sustained
response to antiviral therapy and characterization of mechanisms of non-
responsiveness and development of resistance to therapy.
Determination of the impact of genetics and co-factors, e.g., other viruses
and their therapies, drug and alcohol use, metabolism errors, etc., on viral
replication and its response to anti-viral therapies.
2. Characterization of the host's immune responses to infection:
Definition of the immunological phenomena that accompany the early natural
history, i.e., acute infection and the first 5 years of chronic infection.
Studies on the mechanisms by which HCV evades the immune system and sets up
chronic infection as well as studies on the mechanisms for maintenance of
chronic infection.
Characterization of the mechanisms of protective immunity, the specific
epitopes of HCV involved in protective immune responses, and surrogate
markers of protective efficacy. Characterization of the factors that are
deficient in protecting against reinfection.
Definition of protective as well as injurious cellular mediated immune-
responses and the balance between them.
Identification of immunological mechanisms associated with chronic infection,
as well as how these are modulated by co-infections with hepatitis B virus
(HBV), human immunodeficiency virus (HIV) and other viral agents.
Assessment of the effects of drug and alcohol use on immunological mechanisms
associated with recovery from hepatitis C as well as evolution to chronicity.
Characterization of the unique role of the intrahepatic immune system in
determining the course and outcome of HCV infection, as well as the role of
modulating factors on this system.
3. The understanding of the pathogenic mechanisms and disease progression:
Definition of viral and host factors that contribute to the pathogenesis of
HCV infection and to each of the stages of disease progression: acute
infection, chronic infection, progression of fibrosis, evolution to cirrhosis
and development of HCC.
Identification of biomarkers for disease progression, as well as non-invasive
markers for fibrosis, cirrhosis and cancer.
Characterization of the impact of factors such as age, race/ethnicity, and
gender and co-factors such as HIV, immune suppression, environmental factors,
obesity, drug and alcohol use on the establishment of the disease as well as
the mechanisms by which they contribute to progression of chronic liver
disease.
Definition of the mechanisms for spontaneous recovery from chronic infection
with HCV.
Characterization of the molecular pathogenesis of cancer secondary to HCV
infection.
Studies on the pathogenesis of clinical and biochemical manifestations of
both hepatic and extrahepatic disease, including cryoglobulinemia,
glomerulonephritis, keratoconjunctivitis sicca, and arthritis.
Studies on the molecular and cell biologic mechanisms by which hepatitis C
causes symptoms of fatigue.
Analysis of the molecular basis for efficacy of novel drugs and active and
passive immune-therapies.
4. The development of research resources and approaches to characterize the
pathophysiology of HCV infection:
Development of fully permissive tissue culture systems that supports the
viral life cycle.
Development of characterized, representative small animal models: to support
experimental studies of the pathogenesis of HCV from infection through
cancer, in liver and extra-hepatic organs and to evaluate the safety and
efficacy of proposed antiviral therapies, immunotherapies, and disease-based
therapies and vaccines to prevent or eradicate disease including HCC.
5. The development of novel vaccines and therapies against HCV.
Development of vaccines using conventional as well as innnovative approaches
to inducing humoral and cellular immune responses to HCV.
Evaluation of efficacy of novel vaccines in animal models of HCV infection.
Development of molecular approaches to therapy of hepatitis C, including use
of antisense molecules, siRNAs, and gene therapeutic approaches.
Development of small molecules with activity against HCV and related viruses
that might be later evaluated in man.
MECHANISM OF SUPPORT
This RFA will use NIH R01 and R21 award mechanism(s). 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,
R01 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 2003.
The exploratory/developmental grant (R21) mechanism provides short-duration
support for preliminary studies of a highly speculative or innovative nature
which are expected to yield, within the 2 year time frame, sufficient
information upon which to base a well-planned and rigorously defined series
of further investigations.
Projects will be limited to $100,000 direct costs per year and are limited to
two years duration. These grants will not be renewable; competing
continuation applications will not be accepted. Continuation of projects
developed under this program will be through the regular research grant
mechanism (for example, R01).
This RFA uses just-in-time concepts. It also uses the modular budgeting
format. (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.
FUNDS AVAILABLE
The participating IC(s) intend to commit approximately $6 million in FY 2003
to fund 17 to 22 new and continuing grants in response to this RFA. An
applicant may request a project period of up to 5 years and a budget for
direct costs of up to $250,000 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 IC(s) 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 underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research and financial or grants management issues:
o Direct your questions about scientific/research issues to:
Jose Serrano M.D., Ph.D.
Director, Liver and Biliary Programs
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Rm. 657
Bethesda, MD 20892-5450
Telephone 301 594-8871
FAX: 301 480-8300
Email: js362q@nih.gov
John S. Cole, III, Ph.D.
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, Suite 5000
Bethesda, MD 20892-7398
Telephone: (301) 496-1718
FAX: 301-496-2025
Email: jc121b@nih.gov
Luiz H. Barbosa, D.V.M.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
7601 Rockledge Drive, Rm. 10146
Bethesda, MD 20817
Telephone: 301-435-0075
FAX: 301-480-0868
Email: barbosal@nih.gov
Diane L. Lucas, Ph.D.
Program Director
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Blvd., Rm. 402
Bethesda, MD 20892-7003
Telephone: 301-443-8744
Fax: 301-594-0673
Email: dlucas@nih.gov
Leslye D. Johnson, Ph.D.
Chief, Enteric and Hepatitis Diseases Branch
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
6610 Rockledge Dr., Rm. 4015
Bethesda, MD 20892
Telephone: 301-496-7051
FAX: 301-402-1456
Email: ljohnson@niaid.nih.gov
Tom Kresina, Ph.D.
Deputy Director
Center on AIDS and Other Consequences of Drug Abuse
National Institute on Drug Abuse
6001 Executive Blvd., Rm. 5200
Bethesda, MD 20892
Telephone: 301-402-1913
FAX 301 594-6566
Email: tk13v@nih.gov
o Direct your questions about financial or grants management matters to:
Ms. Donna Huggins
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Rm. 711
Bethesda, MD 20892-5456
Telephone: 301-594-8848
FAX: 301-480-3504
Email: dh48v@nih.gov
Mr. Bill Wells
Grants Management Specialist
National Cancer Institute
6120 Executive Blvd. Rm. 243
Bethesda, MD 20892
Telephone: 301-496-8796
FAX: 301-496-8601
Email: ww14j@nih.gov
Ms. Shelia Ortiz
Grants Management Specialist
Division of Extramural Affairs
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Rm. 7171
Bethesda, MD 20817
Telephone: 301-435-0166
FAX: 301-480-3310
Email: ortizs@nih.gov
Mr. Judy Fox
Chief, Grants Management Branch
National Institute of Alcohol Abuse and Alcoholism
6000 Executive Blvd., Suite 504
Bethesda, MD 20892-7003
Telephone: 301-443-4704
FAX: 301-443-3891
Email: jsimons@nih.gov
Lesia A. Norwood
Grants Management Officer
Grants Management Branch
Division of Extramural Activities
National Institute of Allergy and Infectious Disease, NIH
6700-B Rockledge Drive, MSC 7614, Room 2117
Bethesda, MD 20892-7614 (Express Zip 20817)
Telephone: 301-402-7146
FAX: 301-480-3780
Email: ln5t@nih.gov
Gary Fleming, J.D., M.A.
Chief, Grants Management Branch
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone: (301) 443-6710
FAX: (301) 594-6849
Email: gf6s@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit, by March 11, 2003, 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 to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Blvd., Rm. 752
Bethesda, MD 20892-5452
Telephone: 301-594-8897
FAX: 301-480-3505
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) 710-0267,
Email: GrantsInfo@nih.gov.
SPECIFIC INSTRUCTIONS FOR R21 APPLICATIONS
All application instructions outlined in the PHS 398 application kit are to
be followed, with the following requirements for R21 applications:
1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME"
concepts, with direct costs requested in $25,000 modules, up to the total
direct costs limit of $100,000 per year.
2. Although preliminary data are not required for an R21 application, they
may be included.
3. Sections a-d of the Research Plan of the R21 application may not exceed
15 pages, including tables and figures.
4. R21 appendix materials should be limited, as is consistent with the
exploratory nature of the R21 mechanism, and should not be used to circumvent
the page limit for the research plan. Copies of appendix material will only
be provided to the primary reviewers of the application and will not be
reproduced for wider distribution. The following materials may be included
in the appendix:
o Up to five publications, including manuscripts (submitted or accepted for
publication), abstracts, patents, or other printed materials directly
relevant to the project. These may be stapled as sets.
o Surveys, questionnaires, data collection instruments, and clinical
protocols. These may be stapled as sets.
o Original glossy photographs or color images of gels, micrographs, etc.,
provided that a photocopy (may be reduced in size) is also included within
the 15 page limit of items a-d of the research plan
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, appendix material 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 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.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIDDK.
Incomplete applications will be returned to the applicant without further
consideration. If the application is not responsive to the RFA, CSR staff
will 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 CSR 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 an 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 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.
(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.
o 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: March 11, 2003
Application Receipt Date: April 15, 2003
Peer Review Date: June/July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 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 RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
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. 93.848 (NIDDK), 93.396 (NCI), 93.839 (NHLBI),
93.273 (NIAAA), 93.856 (NIAID), and 93.279 (NIDA) 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)
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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
|
|
|
|
Department of Health and Human Services (HHS)
|
|
|
|
NIH... Turning Discovery Into Health®
|