STRESS AND DRUG ABUSE: EPIDEMIOLOGY, ETIOLOGY, PREVENTION, AND TREATMENT
RELEASE DATE: January 14, 2003 (see correction NOT-DA-03-001)
RFA: DA-04-001
National Institute on Drug Abuse (NIDA)
(http://www.nida.nih.gov)
LETTER OF INTENT RECEIPT DATE: May 19, 2003
APPLICATION RECEIPT DATE: June 18, 2003
THIS REQUEST FOR APPLICATIONS (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 Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The purpose of this RFA is to solicit applications for innovative research on
chronic stress and drug abuse or dependence. Research is encouraged on the
epidemiology, etiology, prevention, and treatment of drug abuse/dependence,
as it relates to either chronic stress or Post Traumatic Stress Disorder
(PTSD). More specifically, research is sought to examine the relationship
between chronic stress or PTSD and drug use, abuse, and dependence. Also of
interest is the relationship between chronic stress or PTSD and
withdrawal/abstinence, remission, and relapse.
The focus of this RFA is on drug abuse or dependence as they relate to
chronic stress, not acute stress. Applications responsive to this RFA
should include clearly articulated definitions of the chronic stress
construct. Chronic stress has been operationalized and measured in various
ways in relevant research. It is incumbent upon applicants to link proposed
projects to a method of assessing/measuring chronic stress that meets
conventional research standards (e.g., replicable, meets psychometric
criteria for reliability) and is appropriate for the type of project that is
proposed. Once developed, PTSD can be considered as a type of chronic stress
(even though it may follow an acute stressor). In contrast to chronic
stress, the construct of PTSD is associated with a generally accepted
definition (i.e., a set of psychiatric diagnostic criteria developed by the
American Psychiatric Association).
Although NIMH is not a direct sponsor of this RFA, research (etiology,
epidemiology, prevention and treatment) on chronic stress and PTSD as related
to mental health and common comorbid conditions (e.g., substance use and
abuse, delinquency, physical health) is of interest to NIMH.
RESEARCH OBJECTIVES
Background and significance
Scientific knowledge about the epidemiology of stress and drug use has been
expanding and advances in this area have been significant. In addition, the
relationship between stress and drug abuse behaviors has been documented in a
number of preclinical studies that focus on the biological and
neurobiological basis of the relationship. For example, findings indicate
that animals will readily self-administer drugs when exposed to stressors.
Human studies that include patients in drug abuse and other health settings
have found that stress is a factor leading both to drug use and escalation of
use to abuse. However, as yet little is known about the relationship
between stress and drug abuse, and the transition from drug use to dependence
from epidemiologic studies of population-based samples. Epidemiologic
studies, particularly those in which longitudinal designs are used, are
critical for advancing the understanding of the pathways from chronic stress
to the initiation of drug use and the development of abuse/dependence.
Both drug use and stress can affect individuals across the life span.
Children and adult victims of sexual and physical abuse or violent assault
consistently report higher use of alcohol and drugs. In turn, it has been
reported that children who are victims of abuse are more likely to engage in
delinquent behavior, crime, and other deviant behavior. Research that uses a
developmental perspective is needed to further understanding of the
relationship between stress and drug abuse across the lifespan, particularly
in childhood and adolescence.
Early childhood stress can have major influences on brain development, which
in turn could directly affect the etiology of drug use behaviors and the
development of abuse and dependence. Despite growing findings from
preclinical studies, more research is needed on how chronic stress and PTSD
in children and adolescents might be manifested in brain alterations that
could increase vulnerability to drug abuse/dependence. Also needed is
research to identify genetic predispositions to stress that might influence
drug abuse behavior.
Given clear links between drug abuse and exposure to chronic stress,
including apparent vulnerability for escalation from use to abuse and
dependence due to chronic stress, research is needed to characterize
neurobiological changes induced by chronic stress that might underlie its
relationship to drug abuse. Some recent findings reveal specific effects of
stress on brain structure and function. Exposure to stress results in a
cascade of biological responses that aids in the assignment of salience to
the stressor, resulting in a behavioral response. Chronic stress might
compromise the normal function of the hypothalamic pituitary adrenal (HPA)
axis. Moreover, chronic stress results in biobehavioral responses that over
time can result in neurobiological changes that can be long-lasting.
A growing number of studies indicate traumatic stress, arising from various
sources, can result in PTSD. In turn, PTSD has been associated with
measurable changes in the brain, including reduction in volume in brain areas
such as the hippocampus. Findings of this type suggest that stress
associated with PTSD, in fact, can be neurotoxic. Yet, it is not entirely
clear if stress causes cell loss, or perhaps if individuals with reduced
volumes in certain brain areas are particularly vulnerable to chronic stress.
Also, the mechanisms by which chronic stress (in individuals with and without
PTSD) might lead to drug abuse remain unknown. In sum, studies are needed to
help understand how stress interacts with brain systems and how related
neurobiological alterations might drive drug abuse behavior, as well as
potentially interfere with treatment.
Research indicates that accumulated stress may be associated with both the
onset and escalation of drug use. That is, the more stressful events or
environments experienced, the greater the likelihood of drug problems. In
fact, findings support the possibility that a threshold of accumulated risk
can be reached beyond which protective factors cease to ameliorate the
effects of stressors. Also, children, adolescents and adults can experience
ongoing stressors that may place them at risk for future drug abuse.
Ongoing stressors include both sub-optimal environments (e.g., homes that are
conflictual and discordant, homes in which a parent, guardian or sibling is a
substance abuser, or neighborhoods with high levels of crime and drug use)
and certain life experiences (e.g., ongoing physical or sexual abuse; living
with chronic pain; repeated or long-term unemployment).
A variety of behavioral interventions to prevent or manage chronic stress
have been produced through research, such as teaching problem-solving and
affect management, restoring one's sense of purpose and meaning, and training
in relaxation and meditation methods. Existing or novel stress management
interventions might be used in the development or refinement of behavioral
interventions for the prevention or treatment of drug abuse in the context of
chronic stress or PTSD.
Findings on individual differences in response to potential stressful events
suggest that moderators and mediators play an important role in the human
stress response. For example, variables such as cognitive appraisal, coping,
personality features, and social relationships have been found to moderate
responses to potentially stressful life events. Models of successful coping
with stress include constructs like resilience, hardiness, and post-traumatic
growth. Given that drug abuse is sometimes conceptualized as a maladaptive
response to stressors, findings on moderators and mediators of stress might
be applied in prevention and treatment research for drug abuse. For
example, the relationship between gender, chronic stress, and drug abuse
needs to be better understood.
Findings on the co-occurrence of drug abuse and PTSD (e.g., 50% of treatment-
seeking drug abusers meet criteria for PTSD during their lifetime) suggest
that PTSD might have particular relevance to the etiology, prevention, and
treatment of drug abuse and dependence. Some studies suggest that drug abuse
may precede PTSD; others suggest that PTSD symptoms function as a "trigger"
for drug use, thereby contributing to the development and maintenance of drug
abuse and dependence as well as relapse. Such research suggests the
potential value of developing interventions to prevent the onset and
escalation of drug abuse in individuals exposed to trauma, even where
questions about causal pathways are not resolved.
Comorbid drug abuse or dependence can complicate existing treatments for
PTSD. Research suggests that individuals with PTSD tend to have poorer
outcomes with existing behavioral drug abuse treatments than those without
PTSD. A number of pharmacotherapies have shown beneficial effects when used
for PTSD. Yet, few medications have been tested for drug abusing individuals
with comorbid PTSD, or tested in combination with behavioral treatments for
such populations.
There is a growing body of literature indicating that stress does not play an
equal role in males and females. In rodents, for example, stress facilitates
classical conditioning in males, but impairs classical conditioning in
females. In humans, males exhibit a greater cortisol response than females
to acute psychological stress, and brain imaging studies have shown that
stressful emotional tasks produce gender differences in regional cerebral
activation patterns. Females have higher lifetime rates of PTSD and there is
considerable evidence for sex differences in coping with stress. The
conditional risk of developing PTSD following trauma exposure is two times
greater in women which is attributable to women having a much greater risk of
PTSD following assaultive violence than men. For women, sexual abuse is
associated with more psychopathology than is physical abuse, but the inverse
relationship holds for men. Among individuals in drug abuse treatment,
females have significantly higher rates of comorbid PTSD than do males, and
PTSD is more likely to precede drug dependence in females than in males.
And, there is evidence that stress many play a larger role in relapse in
females than males. Given such gender differences in PTSD and the impact of
stress, researchers are encouraged therefore to take a gender-based approach
in their study designs and to propose gender-based hypotheses.
In sum, more research is needed to better understand the epidemiologic and
etiological relationships between chronic stress and drug abuse, and how to
prevent and treat drug abuse in individuals experiencing chronic stress.
Similar research needs exist on PTSD as it relates to drug abuse and
dependence.
Investigators interested in chronic stress relative to service delivery,
including organization and financing issues should note PA-01-097, Drug Abuse
Health Services Research
(https://grants.nih.gov/grants/guide/pa-files/PA-01-097.html).
Areas of Research Interest
The examples listed in the sections below illustrate the types of research
that would be responsive to this RFA. Types of research encouraged include
but are not limited to:
Epidemiology
Population-based and clinical research on the extent to which exposure to
chronic stress signals an increase in the risk of drug use, abuse and
dependence is of interest. Epidemiological studies that focus on individual
and environmental factors specific to chronically stressed individuals that
enhance vulnerability to drug use or relapse to drug use are specifically
sought. Studies are sought examining the epidemiology of co-occurring
chronic stress and drug abuse or dependence in the general population. This
includes research investigating moderators of the relationship between these
variables. For example, it is important to understand gender differences in
the effects of chronic stress and the effects of biological and physiological
mechanisms that contribute to differential response to stress. Also, the
identification of "protective" factors that might attenuate the impact of
chronic stress on drug abuse is particularly important due to implications
for prevention and treatment.
o Studies to examine social, cultural and environmental influences on chronic
stress and drug abuse/dependence within and across racial and ethnic groups.
o Differential effects of chronic stress during stages of drug use and the
influence of other co-existing psychiatric disorders.
o The influence of gender on pathways from chronic stress to stages of drug
use.
o Studies to examine the influence of environmental conditions (e.g.,
neighborhood disadvantage, crime, violence) on the co-occurrence of chronic
stress and drug abuse/dependence.
o Studies to examine differential effects of continued, repetitive, traumatic
events on drug use across different age groups, especially during adolescence
and young adulthood (to expand our understanding the relationship between
chronic stress and drug abuse).
Etiology
This RFA encourages human research studies on how chronic stress across the
developmental trajectory (e.g., prenatal, perinatal, childhood, adolescence,
early/mid/late adulthood) affects risk for drug-seeking or drug-taking
behavior and abuse/dependence or relapse. Studies utilizing objective
measures of stress-induced developmental changes are sought. This includes
studies measuring physiological (e.g., pupillary dilation, cortisol
secretion) reactivity to stressful situations or to laboratory events such as
acoustic startle. While such physiological responses to stress currently are
studied, their relationships to vulnerability to drug abuse are virtually
unexplored. Genetic effects are strongly associated with drug abuse as are
environmental effects, but the contribution of each of these factors, and
especially gene-environment interactions, are much less studied and
constitute a research gap. Personality characteristics of children and their
interaction with home (including, for example, foster care) and school
environments constitute one research focus relevant to the gene-environment
question. Less obvious sources of early stress, such as natural disasters
or death of a parent, might be contributory and thus, constitute an important
additional focus for research. Examples include:
o Effect of long-term early stress on adult stress response and drug abuse,
particularly with respect to neurobiological aspects of stress.
o Effects of early stress on neurobiological and neurobehavioral processes in
development, and how changes may place a child or adolescent at risk for drug
abuse.
o Studies on how drug abuse may contribute to or bring about stress (e.g.,
physical or sexual assault, victimization, violence) and/or PTSD.
o Studies on how drugs can be used to "self-medicate" or to produce relief
from stress.
o Objective measures of chronic stress either as a precursor to, or
concurrent with, drug abuse.
o Studies of biological/psychological/environmental/social factors that might
protect an individual from stress and thereby reduce drug abuse risk.
o Investigations of individual differences in response to chronic (external)
stressors and their relation to drug abuse.
o Characterization of etiological effects of early sub-optimal environments
(e.g., orphanages, poverty- or crime-ridden neighborhoods) and later drug
use.
o Determination of the role of chronic stress in drug abuse relapse.
Studies on the neurobiology of trauma, particularly as related to the
subsequent experience of PTSD concurrent with drug abuse
Prevention
Applications are desired for interventions to prevent the onset of drug use
or its escalation to abuse as a result of chronic stress. Interventions can
be delivered in many types of environments, including hospitals, emergency
rooms, faith-based and community organizations, schools, workplaces, etc.
Examples include:
o Development and testing of strategies to prevent drug abuse initiation
among individuals who have experienced long-term physical, sexual, and/or
psychological/emotional abuse.
o Testing community-based interventions designed to prevent onset of use or
escalation to drug abuse among chronically stressed children, youth, and
families living in neighborhoods with characteristics that have been
associated with chronic stress (e.g., crime, victimization, chronic
unemployment, unsafe streets, etc.)
o Testing strategies designed to prevent dependence on prescription drugs in
chronically stressed individuals who live with chronic pain.
o Development and testing of early prevention interventions that target
chronically stressed children who have lived in multiple out-of-home
placements such as foster care, group homes, and institutions.
o Development and testing of strategies for preventing drug abuse conditions
in chronically stressed individuals who are part of minority groups and
communities that may have experienced intergenerational stress or historical
trauma (such as American Indians and African Americans).
Treatment
Research is encouraged on the treatment of drug abusing or dependent
individuals who concurrently are experiencing chronic stress or PTSD. This
includes research on innovative approaches to stop the progression from drug
use to abuse and dependence due to the effects of chronic stress, including
the development and testing of behavioral treatments, alone or in combination
with pharmacotherapies, for drug abusing or dependent individuals with
comorbid PTSD or chronic stress. Given that individuals with the foregoing
problems also can be at high risk for HIV/AIDS and other medical conditions,
research also is encouraged that includes attention relevant to these
factors.
Behavioral treatment and combined behavioral and pharmacological treatment
studies in response to this RFA should be guided by NIDA's Behavioral
Therapies Development Program, PA NUMBER: PA-99-107
https://grants.nih.gov/grants/guide/pa-files/PA-99-107.html. Although PA-99-
107 delineates three stages of behavioral therapy research, this RFA solicits
only applications for Stage I and Stage II studies of all forms of behavioral
treatment, including psychotherapy, relapse prevention, counseling, group
therapy, family therapy, couples therapy, etc. Stage I research involves the
development, modification, and pilot testing of novel behavioral
interventions. Stage I projects also may focus on incorporating novel
technologies (e.g., information technologies such as hand-held computers,
multimedia CD ROM programs, and instant messaging) into behavioral
interventions. Stage II behavioral treatment research involves testing
behavioral interventions and studies that are designed to identify the
efficacious components of behavioral interventions. Behavioral treatment
studies also can extend to the identification of moderators and mediators of
the effects of potentially efficacious components of behavioral
interventions. Treatment research proposals responsive to this RFA should
focus on drug abusing/dependent individuals who also are experiencing chronic
stress or PTSD.
Examples are:
o Enhancement of treatments with existing or novel stress management
interventions.
o Using innovative models of successful coping with stress (e.g., resilience,
toughening) to inform the development of novel treatments.
o Studies to determine if additional trauma-specific interventions enhance
the outcome of treatment when used for drug abusers with PTSD.
o Studies to determine new or more effective ways to combine medications with
behavioral treatments for individuals with concurrent drug use disorders and
PTSD.
o Treatments designed to treat individuals who are dependent upon or abusing
prescription drugs for chronic pain or for other medical conditions that are
associated with chronic stress.
o Treatments to enhance adherence to medication, including medication for
comorbid psychiatric conditions, HIV, or for other infectious disease
o Treatments that incorporate behavioral risk-reduction interventions for HIV
or other infectious diseases for drug abusers who also suffer from chronic
stress.
o Studies of efficacious therapies in which dismantling or additive designs
are used to identify their main active components, and/or the moderators and
mediators of potential effects of active components of efficacious
treatments.
o Studies of the role of chronic stress in behavioral treatment engagement,
retention, and/or maintenance of treatment gains.
o Evaluation of potential efficacy of medications which alter responsiveness
of HPA axis, in combination with behavioral therapy, as potential therapies
for drug dependence.
o Studies examining the value of gender-specific treatment of individuals
with comorbid drug abuse and PTSD
MECHANISM OF SUPPORT
This RFA will use NIH research project grant (R01) award mechanism. As an
applicant you will be solely responsible for planning, directing, and
executing the proposed project. This RFA is a one-time solicitation. Future
unsolicited, competing-continuation applications based on this project will
compete with all investigator-initiated applications and will be reviewed
according to the customary peer review procedures. The anticipated award date
is June 2004.
This RFA uses just-in-time concepts. It also uses the modular as well as the
non-modular budgeting formats (see
https://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
you are submitting an application with direct costs in each year of $250,000
or less, use the modular format. Otherwise follow the instructions for non-
modular research grant applications.
FUNDS AVAILABLE
NIDA intends to commit approximately $2,500,000 in FY 2003 to fund 8 to 10
new grants in response to this RFA. An applicant may request a project period
of up to 5 years. 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 NIDA
provides 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(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 three
areas: scientific/research, peer review, and financial or grants management
issues:
o Direct your questions about scientific/research issues to:
Lisa Onken, Ph.D.
Division of Treatment Research and Development
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 4123, MSC 9551
Bethesda, MD 20892-9551
Telephone: 301-443-2235
Fax: 301-443-8694
E-mail: Lisa_Onken@nih.gov
o Direct your questions about peer review issues to:
Teresa Levitin, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD 20892-9547
Telephone: 301-443-2755
Email: tlevitin@mail.nih.gov
o Direct your questions about financial or grants management matters to:
Gary Fleming, J.D., M.A.
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
E-mail: gfleming@mail.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:
Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD 20892-9547
Rockville, MD 20852 (for express/courier service)
Telephone: 301-443-2755
Fax: 301-443-0538
Email: tlevitin@mail.nih.gov
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
https://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 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
https://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
https://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:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the Checklist, and three signed, photocopies, in
one package to:
Center For Scientific Review
National Institutes Of Health/DHHS
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application must be
sent to:
Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD 20892-9547
Rockville, MD 20852 (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 NIDA. Incomplete applications will be returned to the
applicant without further consideration. And, if the application is not
responsive to the RFA, CSR staff may contact the applicant to determine
whether to return the application to the applicant or submit it for review in
competition with unsolicited applications at the next appropriate NIH review
cycle.
Applications that are complete and responsive to the RFA will be evaluated
for scientific and technical merit by an appropriate peer review group
convened by NIDA in accordance with the review criteria stated below. As
part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications under
review, will be discussed and assigned a priority score
o Receive a second level review by the National Advisory Council on
Drug Abuse
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 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: May 19, 2003
Application Receipt Date: June 18, 2003
Peer Review Date: November/December 2003
Council Review: February 2004
Earliest Anticipated Start Date: June 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
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components
involving Phases 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: https://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
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
https://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
https://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
https://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 https://grants.nih.gov/grants/stem_cells.htm and at
https://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.
HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG
ABUSE: Researchers funded by NIDA who are conducting research in community
outreach settings, clinical, hospital settings, or clinical laboratories and
have ongoing contact with clients at risk for HIV infection, are strongly
encouraged to provide HIV risk reduction education and counseling. HIV
counseling should include offering HIV testing available on-site or by
referral to other HIV testing service for persons at risk for HIV infection
including injecting drug users, crack cocaine users, and sexually active drug
users and their sexual partners. For more information see
https://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html.
NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS: The National Advisory Council on
Drug Abuse recognizes the importance of research involving the administration
of drugs to human subjects and has developed guidelines relevant to such
research. Potential applicants are encouraged to obtain and review these
recommendations of Council before submitting an application that will
administer compounds to human subjects. The guidelines are available on
NIDA's Home Page at http://www.nida.nih.gov under the Funding, or may be obtained by
calling (301) 443-2755.
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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This
RFA is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.279, and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under authorization of Sections 301
and 405 of the Public Health Service Act as amended (42 USC 241 and 284 and
administered under NIH grants policies described at
https://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.