RELEASE DATE:  April 21, 2003

PA NUMBER:  PA-03-111 (This PA has been reissued, see PA-06-324 for R01 applications)

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 using 
the electronic SF424 (R&R) application. 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 thereafter. Applications relating to R33 and R34 
activities must be in response to NIH Institute/Center (IC)-specific announcements.

EXPIRATION DATE: March 02, 2006

National Institute of Mental Health (NIMH)



o  Purpose of the PA
o  Research Objectives
o  Mechanism(s) 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 PA replaces PA-00-016.

Maximal benefits from treatment or preventive interventions will not be 
achieved if individuals discontinue those interventions before completion.  
Even if a protocol is completed, less than full adherence to one or more of its 
components can also limit the benefits.  An example of the consequences of 
nonadherence to treatment regimens may be seen in statistics relating to 
unipolar major depression.  According to World Health Organization estimates, 
unipolar major depression will become the second leading cause of disability 
worldwide by the year 2020.  Although effective treatments exist, large 
segments of those who suffer from depression do not receive treatment.  The 
Agency for Healthcare Research and Quality estimates that, among those who do 
receive treatment with available antidepressant medications, forty percent do 
not complete the recommended 7-12 months regimen.  Thus, the full benefit of 
antidepressant medication therapy is not realized.  Similarly, substantial 
dropout rates from psychosocial and behavioral interventions for mental 
disorders limit their public health impact.  In addition to unipolar major 
depression, bipolar disorder, schizophrenia, and anxiety disorders such as 
obsessive-compulsive disorders are among the leading causes of disability 
worldwide.  Available interventions for these disorders could have greater 
impact and relieve more suffering if adherence to them were improved.

This program announcement is intended to expand research on adherence and 
behavior change that leads to improved adherence and/or improved mental health 
outcomes.  It should integrate findings from the basic behavioral sciences with 
interventions for mental disorders, symptoms, or related disability, and with 
findings from services research about the elements of care delivery systems that 
facilitate or create barriers to improved adherence.  Included are studies of 
mechanisms and processes that enhance or interfere with adherence to preventive, 
treatment, and rehabilitative interventions.  The interventions may be 
pharmacological, behavioral, or psychosocial.  Emphasis is on the development 
of innovative approaches to adherence and behavior change, especially models of
interventions to improve adherence.  A well-articulated, empirically based 
conceptual framework is therefore essential in applications solicited under 
this announcement.  Applications that also include a detailed plan for initial 
tests of a conceptual model, or which test the feasibility of implementing an 
efficacious intervention in an existing health care delivery system are 
especially encouraged.

One commonly used definition of adherence is: The degree to which a patient or 
client's behavior is consistent with an agreed-upon mode of treatment.  However, 
the definition of "adherence" or "behavior change" might well vary depending 
upon the nature and scope of the particular problems under study.  Clear 
conceptual and operational definitions and psychometrically sound measures 
that are consistent with these definitions are essential in this research.  
Definitions of "adherence" or "behavior change" might address, for example, 
the completeness and frequency with which a client engages in behavioral or 
psychosocial components of an intervention protocol, or the extent to which a 
client takes medications at the dosage and frequency prescribed.  Other 
definitions and measures could focus on provider behaviors, intervention 
strategies or on aspects of the patient – provider relationship.

Increased understanding of the mechanisms and processes underlying individuals' 
decisions to adhere or not to adhere to interventions for mental disorders, 
their symptoms, and related disability, would enhance our ability to develop 
models of interventions to modify those mechanisms and processes to increase 
adherence.  Although many theoretical models have been developed to describe 
the processes of adherence and behavior change, their potential has not been 
fully exploited to guide the design of pharmacological, behavioral and 
psychosocial interventions.  Progress in applied public mental health could be 
accelerated significantly by building on fundamental research in the behavioral 
and biomedical sciences related to motivation, persuasion, attitude change, 
decision-making, perception, self-efficacy, social cognition and other 
interpersonal processes, initiation and sustainment of behavior change, 
personality factors, family and community support, and the character of 
alliances between providers and clients.  Therefore, investigation of the 
utility of such theoretical models remains an important challenge.

Applications examining mechanisms and processes underlying provider strategies 
and behaviors that enhance recruitment, retention, and adherence are also 
encouraged.  Other areas of interest under this program announcement include 
research on approaches to decreasing stigma related to mental disorders and 
increasing adherence to interventions; studies of ways in which various 
informed consent procedures and other issues related to research ethics can 
facilitate or hinder adherence to interventions; and the development of 
reliable and valid measures for all the above areas.

The importance of adherence to the outcome of preventive, treatment, and 
rehabilitative interventions is well recognized, but it has often been treated 
simply as a nuisance variable in research.  Adherence must be regarded as a 
central focus in all research that attempts to develop or test models of 
interventions for mental disorders, symptoms, and related disability.


The need for research is urgent across a range of topics germane to adherence 
to interventions for mental disorders, symptoms, and related disability.  This 
program announcement will encourage grant applications for research in a number 
of critical areas, including, but not limited to:

o  Cross-cutting principles of motivating adherence and behavior change in 
studies aimed at developing models of preventive, treatment, and rehabilitative 
interventions and innovative strategies to enhance adherence to them;

o  Methods of adherence and behavior change that promote incremental change over 
time to sustain the benefits of intervention;

o  The relationship of adherence to intervention response throughout the course 
of the intervention;

o  How competing theories of adherence and behavior change complement each 
other, such as studies simultaneously varying motivation source, degree of 
self-efficacy, stage of change, social reinforcement, or norms;

o  How differential patterns of adherence to various components of combined 
interventions influence outcomes;

o  Identifying the general principles of motivation (e.g., intrinsic or
extrinsic motivation) most effective in encouraging adherence, and identifying 
the emotions, attitudes, states, or beliefs (e.g., negative emotions such as 
fear, or positive attitudes such as an enhanced self-image or an appeal to an 
ideal self) that are most centrally associated with adherence behaviors;

o  Studies of various theory-based interventions for improving adherence in 
various under-served or high-risk/special-need populations across the 

o  Strategies containing sub-components that address different adherence-
related behaviors separately, e.g., a project with multiple sub-studies that 
investigate different aspects of a theory for their relevance to different 

o  Studies of how factors underlying adherence or behavior change in one domain, 
for example, interventions aimed at HIV disease, other sexually transmitted 
diseases, Hepatitis C and tuberculosis, might inform adherence to interventions 
aimed at mental disorders;

o  Studies of factors underlying provider strategies and behaviors that enhance 
recruitment, retention, and adherence;

o  Developing and validating measurements of adherence to pharmacological, 
behavioral, or psychosocial interventions, including blood and urine levels, 
self-reports, clinicians' observations, pill counts, remote or automated 
sensing devices, etc.;

o  Clarifying the characteristics of study participants that may contribute to 
adherence and non-adherence, such as age, gender, ethnicity, level of education, 
occupation, marital status, parental status, socioeconomic status, sexual 
orientation, religion, personality traits, personal and/or cultural beliefs 
about health, the nature of their disorder, or their treatments, and the
presence of co-morbid mental illness;

o  The health provider/client alliance and communication patterns, and how these 
processes affect adherence;

o  Studies of interventions and service models that aim to increase client 
involvement in preventive, treatment, and rehabilitative decisions as a way of 
improving adherence;

o  Studies that examine the impact of organizational, management, integration, 
or financial features of the mental health delivery system that may facilitate 
or create barriers to improved adherence and/or more productive health 
provider/client alliances;

o  Community and clinical epidemiological studies that assess the relative 
impact of the competing explanatory domains that are associated with adherence, 
such as the relative impact of intra-psychic phenomena, behavioral cues and 
reminders, the health provider/client alliance, or the features of the health 
care delivery system;

o  Research on approaches to decreasing stigma related to mental disorders and 
increasing adherence to interventions, including studies of self stigma, stigma 
among providers, families and significant others, the social context of stigma, 
as well as studies of individuals who are stigmatized; or

o  Research on the potential positive and/or negative impact of various 
informed-consent procedures and other issues related to research ethics on 
interventions aimed at mental disorders, including issues such as capacity to 
make informed consent, adequacy of informed consent content and procedures, 
efforts to identify and reduce therapeutic misconceptions, the impact of 
wash-out protocols, and the feasibility and adequacy of connect by proxies.


This PA will use the NIH Small Research Grant Program (R03), NIH  
Exploratory/Developmental Research Grant Award (R21), and Research Project Grant 
(R01) award mechanism(s).  As an applicant, you will be solely responsible for 
planning, directing, and executing the proposed project.

The Small Grant (R03) provides two years of funding with a maximum of $50,000 
direct costs for each year.  Information on the requirements for the NIH Small 
Grant may be obtained at

The Exploratory/Developmental Grant (R21) provides two years of funding with a 
maximum of $275,000 direct costs over the entire budget period; it is intended 
for pilot testing of interventions and other aspects of intervention 
development. The Research Plan may not exceed 15 pages.  Information on the 
requirements for the NIH Exploratory/Developmental Grant may be obtained at    

The Research Project Grant (R01) provides up to five years of funding that is 
commensurate with the science proposed.

This PA uses just-in-time concepts.  It also uses the modular budgeting format. 
(see  Specifically, 
if you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  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 following 

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


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.


We encourage your inquiries concerning this PA 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 

o  Direct your questions about scientific/research issues to:

William Riley, Ph.D.
Division of AIDS and Health and Behavior Research
National Institute of Mental Health
6001 Executive Boulevard, Room 6226, MSC 9623
Bethesda, MD 20892-9623
Telephone: (301) 435-0301
FAX: (301) 480-2920

Junius Gonzales, M.D.
Division of Services Research and Clinical Epidemiology Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 7141, MSC 9631
Bethesda, MD  20892
Telephone:  (301) 443-3364
FAX:  (301)443-4045
o  Direct your questions about financial or grants management matters to:

Brian Albertini
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6135, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-0004
FAX:  (301) 443-6885


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 

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

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. includes step-by-step guidance 
for preparing modular grants.  Additional information on modular grants is 
available at

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

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

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

APPLICATION PROCESSING:  Applications must be received by or mailed on or 
before the receipt dates described at  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 critique.

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


Applications submitted for this PA will be assigned on the basis of established 
PHS referral guidelines.  An appropriate scientific review group convened in 
accordance with the standard NIH peer review procedures 
( 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 
or board


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, an investigator may propose to carry out important 
work that by its nature is not innovative but is essential to move a field 

SIGNIFICANCE:  Does this study address an important problem?  If the aims of the 
application are achieved, how will scientific knowledge be advanced?  What will 
be the effect of these studies on the concepts or methods that drive this field?

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION:  Does the project employ novel concepts, approaches or methods? Are 
the aims original and innovative?  Does the project challenge existing 
paradigms or develop new methodologies or technologies?

INVESTIGATOR:  Is the investigator appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

ENVIRONMENT:  Does the scientific environment in which the work will be done 
contribute to the probability of success?  Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements?  Is there evidence of institutional support?  

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

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).

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, 

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


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.

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:

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 (
-001.html); 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 differences.

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

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

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.

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 
( 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 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 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

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

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