BIOBEHAVIORAL PAIN RESEARCH
RELEASE DATE: July 11, 2003 (see correction NOT-NR-03-001)
PA NUMBER: PA-03-152
March 2, 2006 (NOT-OD-06-046) Effective with the June 1, 2006 submission date,
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. This announcement will stay active for
only the May 1, 2006 AIDS and AIDS-related application submission date for these
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms
expires on the date indicated below. Other mechanisms relating to this announcement
will continue to be accepted using paper PHS 398 applications until the stated
expiration date below, or transition to electronic application submission. Parent
R03 (PA-06-180) and R21 (PA-06-181) funding opportunity announcements have been
issued for the submission date of June 1, 2006 and submission dates for AIDS and
non-AIDS applications thereafter. Applications relating to R33 and R34 activities
must be in response to NIH Institute/Center (IC)-specific announcements.
EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006
EXPIRATION DATE for All R01 Applications: July 30, 2006, unless reissued.
National Institute of Nursing Research (NINR)
National Institute on Aging (NIA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Cancer Institute (NCI)
National Institute of Child Health and Human Development (NICHD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Alternative Medicine (NCCAM)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.361 (NINR); 93.866
(NIA); 93.846 (NIAMS); 93.399 (NCI); 93.865, 93.929 (NICHD); 93.121 (NIDCR);
93.279 (NIDA); 93.242 (NIMH); 93.853 (NINDS); 93.213 (NCCAM)
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanisms of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
This program announcement replaces PA-99-021, which was published in the NIH
Guide on November 27, 1998.
PURPOSE OF THIS PA
The purpose of this biobehavioral pain research program announcement (PA) is
to inform the scientific community of the interests of the various institutes
at the National Institutes of Health (NIH) and to stimulate and foster a wide
range of basic and clinical studies on pain as they relate to the missions of
Applications are encouraged to study individual differences in pain responses
that may be due to factors such as genetic differences, endocrine activity,
neural activity, immune function, psychological state, developmental stage,
cognitive capacity, disability state, age, gender, social context and cultural
background. The pain experience needs to be examined at all levels of research
including the gene, molecule, cell, organ, and individual with the goal of
developing biobehavioral interventions to manage or prevent pain.
Pain is a critical national health problem. It is the most common reason for
medical appointments, nearly 40 million visits annually, and costs this
country over $100 billion each year in health care and lost productivity.
Pain has a profound effect on the quality of human life. In addition to
possible deleterious effects on immune function, pain can cause disruptions in
sleep, eating, mobility, and overall functional status. In the hospitalized
patient, pain may be associated with increased length of stay, longer recovery
time, and poorer patient outcomes, all of which have health care quality and
Progress is being made in understanding the neuroanatomical pathways and the
neurophysiological and neurochemical mechanisms involved in pain. However,
understanding the subjective pain experience in individuals presents unique
scientific challenges. Even though the basic physiology may be similar,
people react in very different ways, perhaps due to genetic differences,
endocrine activity, neural activity, immune function, stress, psychological
state, developmental stage, age, gender, and cultural background. Thus, the
pain experience needs to be examined at all levels of basic, clinical and
biopsychosocial research with attention to the gene, molecule, cell, organ,
and individual, including the individual as a member of a socio-cultural
context. The goal of increased understanding of the pain experience is to
develop biobehavioral interventions to manage or prevent pain.
Since 1994, NIH has been developing a research agenda dedicated to the
identification of research needs from a broad spectrum of the scientific
community expert in pain research. At that time, ten NIH institutes sponsored
a workshop, "Biobehavioral Pain Research: A Multi-Institute Assessment of
Cross-Cutting Issues and Research Needs," under the aegis of the NIH Health
and Behavior Coordinating Committee. More recently, several institutes and the
FDA co-sponsored a State-of-the Science Conference on Pain, Depression and
Fatigue in Cancer (2002) that reiterated the need for an ongoing research
agenda that will improve both the assessment and management of pain as well
as its interactions with other symptoms. In the intervening years, a rich
variety of research has occurred, but more needs to be accomplished.
The following topics and study areas are not intended to be comprehensive or
exclusive. In virtually all areas of research, however, given the growing
body of research demonstrating gender differences in the experience and
treatment of pain, as well as the genetic, molecular and neurochemical basis
of pain, researchers are strongly recommended to develop gender-based
research designs and to propose gender-based hypotheses.
These pain research areas cut across Institutes and programs and should not
be viewed as restricted to only one specific Institute. Current NIH referral
guidelines will be used to assign grant applications to the most appropriate
NIH Institute based on the scientific focus of the application.
The following topics and study areas are not intended to be comprehensive or
Understanding Critical Interfaces Between Biology and Behavior
o Explore the neural basis of pain perception.
o Examine the neuroendocrine and immunological correlates of pain.
o Investigate relationships between pharmacological and behavioral
interventions, including both conventional and complementary and alternative
medicine (CAM) therapies, to prevent pain.
o Use neuroimaging to study structural and functional correlates of pain
o Explore developmental aspects of pain processing, in particular approaches
that could have an impact upon the treatment of pain across the life span.
o Identify genes relevant to pain and pain inhibitory mechanisms, such as
those that may account for differences in pain experiences and responses to
o Develop models for the use of gene therapy to reduce pain, including the
targeting of neurons or glial cells within the CNS.
o Examine the use of targeted neurotoxins to kill pharmacologically specific
cells within the pain detection/modulation pathways (e.g. target c-fibers
with VR-1's within the dorsal horn of the spinal cord).
Pain, Suffering, and Emotion
o Explore basic mechanisms of the conscious perception of pain and the
affective responses to pain.
o Examine the relative importance of biological, behavioral, developmental,
psychological, environmental, and sociocultural variables in explaining
variations in the course of pain, pain perception, pain dysfunction, response
to treatment and pain-expressive behaviors.
o Clarify the relationships among a variety of emotional states (e.g., anger,
fear, anxiety and depression), which are associated with acute and chronic
pain conditions, and determine how these cognitive states modify the
experience of pain and treatment outcomes.
o Develop reliable and valid measures and strategies for predicting and
intervening with persons simultaneously afflicted with pain and depression,
based upon knowledge of the relationship between biological factors,
characteristics of pain (e.g., location, quality, timing), environmental
circumstances, and psychosocial characteristics.
Pain and Behavior
o Explore the sensory, cognitive, and affective aspects of acute and chronic
pain across the lifespan.
o Elucidate the interaction of biological markers, central nervous system
mechanisms, and drug, behavioral, and CAM interventions.
o Develop methods for assessing relative contributions of biological,
psychological, behavioral, and environmental predictors of the course of pain,
pain dysfunction, and response to treatment for pain in defined problem areas.
o Examine addiction risk in patients taking controlled drugs for pain; the
role of tolerance, addiction and dependence in the consumption of these drugs;
and implications of long-term use in noncancer disease states.
o Explore the use of virtual reality technologies as distractors/relaxers in
the treatment of various types of pain (e.g., burn pain, dental pain).
o Evaluate research strategies to integrate medical, rehabilitation, nursing,
dental, neurological, pharmacological, psychosocial, behavioral, and CAM
treatments for pain problems. Compare the relative effectiveness of each mode
of treatment, and combined treatments, and their potentiating effects on
multiple outcomes. These outcomes include pain along with fatigue, sleep
deprivation, physical functioning, and/or psychological functioning. The
impact of the treatment(s) upon health care utilization and costs may also be
examined in light of the physical and psychological outcomes.
o Develop and refine biobehavioral techniques for optimizing adherence to
pain management. Identify and consider barriers to adherence to pain
o Conduct research on the mechanisms and process variables that are
responsible for the efficacy of behavioral interventions. This research
includes studies to understand better the effect of patients' expectations and
beliefs, psychophysiological states (e.g., anxiety, relaxation, stress),
adherence, and specific cognitive (e.g., imagery) and sociocultural (e.g.,
support systems) components in behavioral interventions.
o Determine which behavioral treatments are most effective for specific
subgroups of patients differentiated by factors such as age, developmental
stage, gender, race, ethnic group, level of dysfunction, or psychosocial
o Conduct clinical trials of cognitive/behavioral pain control methods and
combinations of medical, pharmacological, cognitive/behavioral, and CAM pain
control methods. Examples of CAM therapies for pain control include, but are
not limited to, massage, spinal manipulations, acupuncture, yoga, and
o Establish dose-response curves for biobehavioral interventions.
o Test interventions to improve health care practice in such areas as pain
assessment, identification of barriers to pain management, analgesic
management, pain prevention, and rehabilitation. Attention should be paid to
the cultural competence of interventions.
Commonalities and Differences in Pain Expression, Experience, and Treatment
o Study cognitive factors in the experience of pain, disability, and pain
behaviors across disorders, including such factors as self-efficacy, perceived
control, and pain beliefs.
o Establish the biological/organic, psychosocial, and environmental factors
that may cause progression from acute pain to chronic pain and then to a
chronic pain-related disability.
o Refine existing techniques for measuring pain and develop new techniques
that are disease- and outcome-specific for different populations.
o Determine the supraspinal mechanisms of pain modulation, determine the
effects of specific pain treatments on these central nervous system processes,
and apply new findings on CNS plasticity to the understanding of pain.
o Examine the interrelationships between pain and other symptoms and
comorbidities (e.g., fatigue, sleep alterations, nausea, vomiting, anxiety,
mood disorders, physical deconditioning, stress).
Pain in Diverse and other Special Populations
o Test culturally sensitive approaches to pain assessment and management,
including appropriate methods for translation of the instruments into other
languages and validation among speakers of languages other than English.
Instrument development and validation among persons of various literacy levels
and users of dialects other than standard English is also of interest.
o Develop and test biobehavioral pain interventions for persons of various
ethnic minority groups (including immigrants and refugees), either as a unique
study or comparing interventions and outcomes across populations.
o Investigate pharmacotherapies and biobehavioral pain management for special
populations including infants, children, elderly, cognitively impaired,
disabled, chronically and terminally ill, substance abusers (especially those
with pain disorders), and patients with psychiatric diagnoses.
o Investigate the prevalence and effectiveness of the use of complementary
and alternative therapies for pain treatment in diverse populations such as
ethnic minority groups, the elderly, the terminally ill, patients with HIV-
AIDS and patients with other acute and chronic illnesses that are associated
o Determine effective biobehavioral interventions for HIV- and AIDS-related
pain and explore alterations in nociceptive mechanisms and pain perception.
Pain prevalence, scope and severity of pain in the HIV-infected, and
variations in nociceptive mechanisms depending on primary HIV/AIDS treatment
regimen are also of interest.
o Elucidate the interaction of pharmacotherapies and behavioral treatments
with anti-retroviral treatment in HIV-infected persons.
o Investigate the roles of sleep and circadian variation in the precipitation
and modulation of pain in populations who have special rest - activity needs
such as infants, children, elderly, pregnant women, night-shift workers. This
research could include studies of the effect of pain and its pharmacological
treatment on sleep and daytime alertness, as well as the effects of disturbed
sleep on pain and pain perception. Studies of seasonal and other variations
are also appropriate.
o Test and evaluate pharmacotherapies, behavioral, and CAM treatments in
patients with current and past histories of addiction, including infants born
to drug-, alcohol-, and tobacco-dependent mothers.
o Investigate the effectiveness of biobehavioral pain management in
terminally ill and dying patients.
o Conduct research on co-morbid mental disorders and pain, including
descriptive studies of risk and protective processes as well as interventions
aimed at relieving adverse consequences associated with co-morbid mental
disorders and pain.
o Study the interrelationship of Axis II, as well as Axis I, psychiatric
disorders (e.g., borderline personality, histrionic, antisocial) and chronic
pain, and relate these findings to pharmacological and behavioral therapies.
o Explore the mechanisms that underlie gender differences in the pain
response, e.g., genetic, molecular, hormonal, immunological, and,
o Explore the role of the menstrual/estrus cycle on the pain experience,
e.g., pain perception, pain threshold, development of chronic pain, and pain
o Investigate biobehavioral approaches to managing pain associated with
acute and chronic illness such as arthritis, fibromyalgia, cancer, diabetes,
sickle cell disease, low back pain, headaches, temporomandibular disorders,
and other orofacial pain conditions.
MECHANISMS OF SUPPORT
This PA will use the NIH R01 and R21 award mechanisms. As an applicant, you
will be solely responsible for planning, directing, and executing the proposed
project. The objective of the R01 mechanism is to support a discrete,
specified circumscribed project. The objective of the
exploratory/developmental mechanism (R21) is to encourage applications from
individuals who are interested in testing innovative or conceptually creative
ideas that are scientifically sound and may advance our understanding of
biobehavioral pain research. Investigators are encouraged to explore the
feasibility of an innovative research question or approach that will provide a
basis for future research projects. Exploratory/developmental grants (R21) are
limited to 2 years of support with a combined budget for direct costs of up
$275,000 for the two year period. For example, the applicant may request
$100,000 in the first year and $175,000 in the second year. The request
should be tailored to the needs of the project. Normally, no more than
$200,000 may be requested in any single year. Please see the NIH-wide R21
program announcement (PA-03-107)
Please see the "Submitting an Application" section for more details.
This PA uses just-in-time concepts. It also uses the modular as well as the
non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
you are submitting an application with direct costs in each year of $250,000
or less, use the modular format. Otherwise follow the instructions for non-
modular research grant applications. This program does not require cost
sharing as defined in the current NIH Grants Policy Statement at
You may submit (an) application(s) if your institution has any of the
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
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 your inquiries concerning this PA 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:
Dr. Martha Hare
Office of Extramural Programs
National Institute of Nursing Research
6701 Democracy Blvd, Room 710, MSC 4870
Bethesda, MD 20892-4870
Telephone: (301) 451-3874
FAX: (301) 480-8260
Dr. Judith A. Finkelstein, Ph.D.
Head, Office of Nutrition
Director, Sensory/Motor Disorders of Aging Program
National Institute on Aging
Neuroscience and Neuropsychology of Aging
Gateway Building, Suite 350
7201 Wisconsin Avenue
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Dr. Deborah N. Ader
Behavior and Prevention Research Program Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza, Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5032
FAX: (301) 480-4543
Dr. Paige A. McDonald
Program Director, Basic Biobehavioral Research Branch
Behavioral Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute, NIH, DHHS
6130 Executive Boulevard, MSC 7363
Executive Plaza North, Room 4062
Bethesda, MD 20892-7363
Telephone: (301) 496-8776
FAX: (301) 435-7547
Dr. Louis Quatrano
Behavioral Sciences and Rehabilitation Engineering
National Institute of Child Health and Human Development
6100 Executive Blvd., 2A03, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 402-4221
FAX: (301) 496-0832
Dr. Patricia Bryant
Clinical, Epidemiology, and Behavioral Research Branch
Division of Population and Health Promotion Sciences
National Institute of Dental and Craniofacial Research
Bldg 45, Room 4AS-43A
Bethesda, MD 20892-6402
Telephone: (301) 594-2095
FAX: (301) 480-8322
Dr. Dave Thomas
National Institute on Drug Abuse
6001 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 443-6975
FAX: (301) 984-2217
Dr. Peter Muehrer
Chief, Health and Behavioral Science Research Branch
Division of Mental Disorders, Behavioral Research, and AIDS
National Institute of Mental Health
National Institutes of Health
6001 Executive Boulevard, MSC 9615
Bethesda, MD 20892-9615
Telephone: (301) 443-4708
FAX: (301) 480-2920
Dr. Linda Porter
Systems and Cognitive Neuroscience
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2113
Bethesda, MD 20892-9521
Rockville, MD 20852 (Courier)
Telephone: (301) 496-9964
FAX: (301) 402-2060
Dr. Nancy Pearson
Neuroscience, Mental Health, NRSA Training Programs
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Room 106, MSC 5475
Bethesda, MD 20892-5475
Telephone: (301) 594-0519
FAX: (301) 480-3621
o Direct your questions about financial or grants management matters to:
Ms. Diane Drew
Office of Grants and Contracts Management
National Institute of Nursing Research
6701 Democracy Blvd, Room 710, MSC 4870
Bethesda, MD 20892-4870
Telephone: (301) 594-2807
FAX: (301) 451-5651
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,
SUPPLEMENTAL INSTRUCTIONS: All instructions for the PHS 398 (rev. 5/2001)
must be followed, with these exceptions:
o Research Plan
Items a - d of the Research Plan (Specific Aims, Background and Significance,
Preliminary Studies, and Research Design and Methods) may not exceed a total
of 15 pages. No preliminary data is required but may be included if it is
available. Please note that a Progress Report is not needed; competing
continuation applications for an exploratory/developmental grant will not be
Appendix. Use the instructions for the appendix detailed in the PHS 398 except
that no more than 5 manuscripts, previously accepted for publication, may be
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 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
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
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 application already reviewed, but
such application must include an Introduction addressing the previous
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 the initial merit review, all applications will:
o Receive a written critique
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 second level review by the appropriate national advisory council
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 the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals:
The scientific review group will address and consider each of 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 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
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
INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?
INVESTIGATOR: Is the investigator appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?
ENVIRONMENT: Does the scientific environment in which the work will be done
contribute to the probability of success? Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following
items will be considered in the determination of scientific merit and the
The NIH R21 exploratory/developmental grant is a mechanism for supporting
novel scientific ideas or new model systems, tools or technologies that have
the potential to significantly advance our knowledge or the status of health-
related research. Because the research plan is limited to 15 pages, an
exploratory/developmental grant application need not have extensive
background material or preliminary information as one might normally expect
in an R01 application. Accordingly, reviewers will focus their evaluation on
the conceptual framework, the level of innovation, and the potential to
significantly advance our knowledge or understanding. Reviewers will place
less emphasis on methodological details and certain indicators traditionally
used in evaluating the scientific merit of R01 applications including
supportive preliminary data. Appropriate justification for the proposed work
can be provided through literature citations, data from other sources, or,
when available, from investigator-generated data. Preliminary data are not
required for R21 applications.
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 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.
DATA SHARING: The adequacy of the proposed plan to share data.
BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research.
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
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.
MONITORING PLAN AND DATA AND SAFETY 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 and Safety Monitoring, NIH Guide for Grants and Contracts, June 12,
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
a complete copy of the updated Guidelines are available at
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
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
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
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
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
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
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
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
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
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