TESTING INTERVENTIONS TO IMPROVE ADHERENCE TO PHARMACOLOGICAL TREATMENT REGIMENS

Release Date:  January 19, 2000

RFA:  OD-00-006

Office of Behavioral and Social Sciences Research
National Cancer Institute
National Human Genome Research Institute
National Heart, Lung, Blood Institute
National Institute on Aging
National Institute on Alcohol Abuse and Alcoholism 
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Child Health and Human Development
National Institute of Dental and Craniofacial Research
National Institute of Diabetes and Digestive Disorders and Kidney 
Disease
National Institute on Drug Abuse
National Institute of Mental Health
National Institute of Nursing Research

Letter of Intent Receipt Date: March 6, 2000
Application Receipt Date: April 6, 2000

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT 
INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS 
THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA

PURPOSE

The Office of Behavioral and Social Sciences Research, National Cancer 
Institute, National Human Genome Research Institute, National Heart, 
Lung, Blood Institute, National Institute on Aging, National Institute 
on Alcohol Abuse and Alcoholism , National Institute of Arthritis and 
Musculoskeletal and Skin Diseases, National Institute of Child Health 
and Human Development, National Institute of Dental and Craniofacial 
Research, National Institute of Diabetes and Digestive Disorders and 
Kidney Disease, National Institute on Drug Abuse, National Institute of 
Mental Health, and the National Institute of Nursing Research invite 
applications for research project (R01) grants in order to encourage 
behavioral and social research on the effectiveness of interventions to 
improve adherence to therapeutic regimens in various settings. 

This RFA is responsive to Congressional Report Language for the FY 2000 
Appropriations that urges “the Office of Behavioral and Social Sciences 
Research [and several NIH Institutes] to stress the need for all 
institutions to fund behavioral and social sciences research to improve 
adherence to medical regimes, exercise and weight reduction programs.” 
The RFA is consistent with and based upon recommendations in several 
recent reviews of the scientific literature and set forth by advisory 
groups to NIH Institutes and Centers.

Applications in response to this RFA must propose research on adherence 
to therapeutic treatment regimens where:

1) the therapeutic regimen includes a pharmacological treatment;
2) the therapeutic regimen must be for an existing illness or 
condition, whether acute or chronic, as opposed to a health 
promotion regimen;
3) the adherence intervention has been (a) demonstrated to be 
efficacious in controlled settings (e.g., laboratories, clinical 
trials), (b) tested only with limited populations (e.g., small 
samples or samples from restricted populations) or with short 
periods of follow-up, or (c) researched on a health condition or 
treatment regimen different from that in the proposed research;
4) the adherence intervention targets individuals, formal or informal 
health-care providers, and/or the social or institutional 
environment; and 
5) there are measurements of (a) the delivery of the specified 
therapeutic regimen and adherence intervention (i.e., treatment 
fidelity) and of (b) adherence to the regimen.

In addition, applicants are encouraged to investigate how to adjust 
interventions to take into account the characteristics of different 
populations as well as people suffering from and receiving treatments 
for multiple acute and/or chronic illnesses and conditions. This RFA is 
an opportunity to conduct research cutting across the traditional 
boundaries of responsibility of the participating NIH Institutes and 
Centers (ICs).

HEALTHY PEOPLE 2000

Each NIH RFA addresses one or more of 22 Health Promotion and Disease 
Prevention priority areas. These areas can be found at 
http://odphp.osophs.dhhs.gov/pubs/hp2000. 

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of state and local governments, and 
eligible agencies of the Federal government. Foreign organizations are 
not eligible. However, foreign organizations may participate if they 
are components of domestic, U.S. organizations or via contractual or 
consortium agreements with domestic, U.S. organizations. Racial/ethnic 
minority individuals, women, and persons with disabilities are 
encouraged to apply as principal investigators. Questions about 
eligibility may be addressed to the program contacts listed in the 
INQUIRIES section.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) regular 
research grant (R01) mechanism. This mechanism supports the full range 
of research from basic to clinical intervention studies, as well as 
health services, policy and surveillance research. The Principal 
Investigator will be responsible for the planning, direction, and 
execution of the proposed research project. Awards will be administered 
according to the most recent NIH Grants Policy Statement.

Specific application instructions have been modified to reflect 
"MODULAR GRANT" and "JUST-IN-TIME" application procedures. Complete and 
detailed instructions and information on Modular Grant applications can 
be found at http://grants.nih.gov/grants/funding/modular/modular.htm 
and in the NIH Guide to Grants and Contracts, December 15, 1998 
(http://grants.nih.gov/grants/guide/notice-files/not98-178.html). For 
this RFA, the budgetary maximum specified in these general instructions 
for Modular Grants should be disregarded. (See FUNDS AVAILABLE.)

FUNDS AVAILABLE

The Office of Behavioral and Social Research is making available 
$3,000,000 for the support of approximately six new research grants in 
response to this RFA. The total project period for an application may 
not exceed five years. Direct costs in the first year of the award may 
not exceed $350,000 and the accumulated direct costs over five years 
may not exceed $1,750,000. Research projects with costs less than 
$350,000 per year are encouraged.

In order to facilitate financial planning of the NIH, applicants are 
strongly encouraged to develop budgets with the same number of modules 
in each year of the award. That is, it is highly desirable to have 
“flat” or “even” budgeting across the years of support. Deviations from 
even budgeting should be well justified. The anticipated award date for 
all applications is September 29, 2000. Funding in response to this RFA 
is dependent upon the receipt of a sufficient number of applications of 
high scientific merit. At this time, it is not known if this RFA will 
be reissued at a future date.

RESEARCH OBJECTIVES

(1) Background

Several recent reports and literature reviews point to the continuing 
need for improving adherence to therapeutic regimens. (See REFERENCES.) 
Adherence rates vary considerably across diseases and treatments, 
measuring instruments, and populations, with rates ranging from 30% to 
60% in many instances. Most researchers agree that at least 50% of 
persons for whom drugs are prescribed fail to receive the full benefit 
through inadequate adherence. As noted by the American Heart 
Association (1997), “the rationale for enhancing [adherence] is based 
on the premise that the patient will get well or stay well if the 
physician, other healthcare providers, and the healthcare organization 
make appropriate recommendations, providing the patient has the 
requisite knowledge, motivation, skills, and resources to follow the 
recommendations.” Lack of adherence to therapeutic regimens may result 
in poorer health for individuals as well as economic costs for their 
health-care organizations and the broader society. 

The reasons for non-adherence are multifaceted and not fully 
understood. Health-care providers, organizational systems, and personal 
factors all play a role in adherence to therapeutic regimens. Thus, to 
understand and eventually improve adherence, conceptual frameworks and 
interventions need to take into account institutional, system, 
situational, interpersonal, and personal factors as well as the 
characteristics of the illness or condition and of the treatment 
regimen.

Research has demonstrated the efficacy of a variety of approaches to 
improving adherence to therapeutic regimens in controlled laboratory or 
field experimental situations, in small, selected samples, or over 
limited periods of time. Less is known about the effectiveness of 
interventions when they are moved from controlled research settings to 
where health care is actually practiced with individuals of varied 
backgrounds over extensive periods of time. How does the success of 
interventions to improve adherence vary across types of health-care 
providers, settings, and persons of varying educational, economic, and 
ethnic backgrounds? What adjustments may be needed to implement 
interventions in the “real world” of health care and under what 
circumstances? 

In addition to research on effectiveness, opportunities may exist for 
research on adapting and assessing the efficacy of promising 
intervention strategies that have been used successfully to improve 
adherence, but in small, selected (e.g., unrepresentative) samples. 
Similarly, behavior-change strategies that have been successful in one 
domain may hold promise for improving adherence to therapeutic regimens 
for other illnesses or health conditions.

(2) Areas of Emphasis

In order to concentrate available resources, this RFA stipulates five 
requirements for research on adherence. Research grant applications 
must address all five requirements to be considered responsive to this 
RFA. Subsequent funding initiatives may be issued to address other 
aspects of adherence. Special emphasis is given to adherence research 
in diverse racial/ethnic and socioeconomic status populations.

1. The therapeutic regimen must include a pharmacological treatment. 
This treatment may be combined with behavioral or other kinds of 
treatments of illnesses or conditions.

2. The therapeutic regimen must be for an existing illness or condition 
as opposed to health promotion regimens. See below for examples of 
diseases or conditions of interest to the participating NIH 
Institutes. While research on changing behaviors to promote health 
is important, it lies outside of the purview of this RFA. The NIH 
does continue to encourage such research. Most recently, several ICs 
joined to solicit such research through the RFA on Innovative 
Approaches to Disease Prevention through Behavior Change, NIH Guide 
to Grants and Contracts, Volume 26, Number 36, October 24, 1997 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-98-002.html).  

3. The research must address either (a) the translation of 
interventions already demonstrated to be efficacious in controlled 
experimental situations to “field” or practice settings or (b) the 
further development of efficacious interventions previously tested 
in small, selected samples or with specific diseases and health 
conditions. The major emphasis of the RFA is on “effectiveness” 
research as opposed to “efficacy” research. The research should be 
aimed at determining if and how efficacious interventions may be 
transported to clinical and community settings. Research on testing 
the applicability or generalizability of interventions to broader 
groups of individuals (e.g., differing in socioeconomic status, 
race, ethnicity, in medical conditions and illnesses) is also 
appropriate. However, proposals to develop interventions de novo 
(i.e., those without a prior history of development in any treatment 
area) fall outside the scope of this RFA. 

4. The intervention may target individuals, formal or informal health-
care providers, and/or the social or health-care environments. 
Interventions may operate on multiple levels and targets in order to 
improve adherence. For example, interventions may attempt to enhance 
adherence by increasing people’s knowledge, skills, and motivation, 
by instructing health-care providers on how to better provide 
information, guidance, or monitoring, by involving the individual’s 
social network, or by altering aspects of the health-care system.  

5. Explicit conceptualization and measurement of the therapeutic 
regimen (i.e., health treatment delivery), the intervention(s) to 
improve adherence, and of adherence behaviors are essential. 
Research projects should include appropriate measures of the 
delivery of the specified therapeutic regimen and adherence 
intervention as well as measures of adherence.

In addition to the preceding five emphases, research projects may 
address such issues as the following:

o    How should the intervention be adjusted to take into account the 
characteristics of different populations? Interventions may not work 
equally well for all persons depending on their educational, economic, 
and cultural backgrounds and circumstances. Are particular groups at 
high risk for non-adherence? How should the intervention take this into 
account?

o  What are the consequences for adherence, if any, of an individual 
suffering from and receiving treatments for multiple illnesses and 
conditions? An intervention may improve adherence for one treatment 
aimed at a specific condition, but it may interfere with adherence to a 
regimen for treating another condition. How do interventions to improve 
adherence to acute conditions interface with therapeutic regimens for 
treating chronic illnesses or conditions (and vice versa)? Research 
investigating situations of multiple morbidity cutting across the 
traditional boundaries of NIH ICs is particularly encouraged.
o    How can the proposed intervention be improved based upon research 
results? Research proposals may include provisions making adjustments 
to the intervention based upon assessing the effectiveness of the 
interventions midway through the grant period. That is, the research 
may be divided into two phases. The first phase would consist of a test 
of the intervention as originally proposed in the application. During 
the second phase, based upon research results obtained during the first 
phase, the researchers may “fine tune” the intervention and assess the 
results of this adjustment.

Several NIH Institutes have joined with OBSSR to support this 
initiative. Examples of topics of interest to specific NIH Institutes 
are given below. These examples are not meant to be an exhaustive list 
of the research of interest to the NIH. Additional topical areas and 
approaches designed to better understand and increase adherence to 
pharmacological therapeutic regimens are welcomed.

NATIONAL CANCER INSTITUTE

NCI is interested in behavioral and social sciences research on 
promoting adherence to therapeutic regimens effective in the management 
of cancer. ATherapeutic regimens@ are broadly defined to include not 
only active anticancer treatments but also post-chemotherapeutic 
administration of compounds to prevent/minimize recurrence and prevent 
post-treatment toxicities (e.g., steroid and growth factor 
administration or reduce sun light exposure post-photodynamic therapy). 
Examples of therapeutic regimens that pose particular problems in 
adherence include but not limited to interferon treatment for melanoma, 
topical application of drugs in mycosis fungoides, oral maintenance 
therapy for ALL and oral treatment regimens in CLL. NCI has special 
interest in promoting research that may lower barriers to effective 
therapy for children and the aged as well as for the underserved.

NATIONAL HUMAN GENOME RESEARCH INSTITUTE

As human genetic research progresses and as more is learned about the 
role that genes play in the development of common disorders, it will 
become increasingly possible to provide individuals with information 
about the genetic contribution to their disorder. Currently, there is 
no data on the impact of genetic information on individuals' adherence 
to therapeutic regimens. Will individuals who are found to have genes 
or genetic markers associated with their own disorder be more, equally, 
or less likely to adhere to proposed therapeutic regimens? The NHGRI, 
through its Ethical, Legal, and Social Implications Research (ELSI) 
program, is interested in supporting research to explore what impact 
individualized information about the genetic contribution to particular 
disorders, including common complex adult-onset disorders, will have on 
an individual's adherence to therapeutic regimens. For example, women 
who are known to be at increased risk to develop breast cancer, due to 
familiy history, BRCA mutations, or other factors, may be put on a 
regimen of tamoxifen or raloxifen. What impact will knowledge of BRCA1 
mutation status have on an individual's adherence to a tamoxifen or 
raloxifen regimen? Special consideration will be given to studies that 
examine the impact of this information on individuals from different 
socio-cultural and socioeconomic groups.
NATIONAL HEART, LUNG, BLOOD INSTITUTE

The NHLBI supports studies that seek to improve rates of adherence to 
medical and behavioral regimens used in preventing and treating heart, 
lung, blood and sleep diseases and disorders. The NHLBI is also 
interested in studies that investigate how psychological, social, 
behavioral, biological, cultural and health care systems factors 
influence adherence. Examples of therapies and conditions where 
adherence poses special problems include antihypertensive therapies, 
cholesterol-lowering medications, medications used to treat myocardial 
infarction and congestive heart failure, and treatments for asthma, 
tuberculosis and sickle cell disease. Areas of special interest include 
effectiveness studies involving development and testing of adherence-
enhancing interventions in health-care and community settings; 
investigations of the cultural, social and health care system factors 
that affect adherence; research on the determinants of and optimal 
approaches to changing provider behavior and practices; and use of new 
technologies (e.g., computer-based approaches) in the measurement and 
promotion of adherence.

NATIONAL INSTITUTE ON AGING

The NIA seeks research on biological, behavioral, cognitive, social and 
economic factors that affect adherence to medications and other 
behavioral regimens in the middle and later years. NIA is interested in 
adherence behavior to both acute and chronic treatment recommendations 
for a broad range of co-morbidities prevalent in old age (e.g., 
Alzheimer’s disease, arthritis, cancer, diabetes, heart disease, 
infectious diseases, stroke). Of special interest is an examination of 
age-related processes and conditions (e.g., multiple medication use, 
multiple morbidities, cognitive changes, transitions in living 
arrangements and social supports, and the nature of provider-patient 
interactions and clinical decision-making) that affect adherence 
behaviors and that are important in the design of appropriate adherence 
interventions for older adults. Psychosocial and economic mediators and 
outcomes of multi-level intervention approaches should be considered. 
For background material and emphasis areas see NIA’s recent program 
announcement PA-99-07 on Diversity in Medication Use and Outcomes in 
Aging Populations - May 1999 that can be can be found on the Web at 
http://www.nih.gov/nia/resfund/bsr.htm.

NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM 

The NIAAA is the lead federal agency responsible for research on the 
causes, consequences, prevention and treatment of alcohol-related 
problems. Research is currently being funded to develop and test 
pharmaceutical agents to treat alcoholism. Of interest is the 
identification of practical, effective techniques to enhance adherence 
to medication regimens, given alone or in combination with psychosocial 
therapy, for the treatment of alcohol abuse and alcohol problems.

NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIAMS is interested in behavioral and social sciences research on 
promoting adherence to therapeutic regimens effective in the management 
of arthritis and other rheumatic diseases, muscle diseases, 
musculoskeletal disorders, bone diseases including osteoporosis, and 
skin diseases. NIAMS has special interest in promoting research which 
may lower barriers to effective therapy for underserved populations.

NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
NICHD is interested in research to elucidate behavioral mechanisms 
involved in adherence to medical and therapeutic regimens for children 
and adolescents with acute and chronic illnesses, injuries, stress and 
pain as well as behavioral and attentional disorders. Of interest are 
intervention studies examining motivational factors and deterrents to 
adherence in children, their parents/caretakers, and health care 
providers.

NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
NIDCR is interested in the development and translation of effective 
interventions to increase adherence to fluoride, antimicrobial, 
antibiotic, analgesic, or other pharmacological regimens used in 
treating oral diseases such as dental caries, periodontal diseases, 
salivary disorders and xerostomia, TMJ disorders, and trigeminal 
neuralgia or other orofacial pain disorders as well as the pain, 
swelling, or inflammation associated with dental procedures or with 
surgeries to correct craniofacial defects. NIDCR is also interested in 
research to increase adherence to treatment regimen involving 
pharmacological approaches to reduce oral complications of systemic 
diseases, such as diabetes or HIV, or oral complications of medical 
interventions, such as chemotherapy or radiation. In addition, research 
projects utilizing oral biomarkers, such as salivary measures, to 
assess or enhance adherence to pharmacological regimens are of specific 
interest to NIDCR. 

NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE DISORDERS AND KIDNEY 
DISEASE

NIDDK is interested in development and translation of effective 
interventions to increase adherence to medical regimens for diabetes, 
obesity, genetic metabolic diseases and endocrine, renal, urologic, 
hematologic, digestive, and liver diseases. Examples of topics of 
interest to NIDDK include: interventions to increase adherence 
behaviors affecting glycemic control and other diabetes outcomes; 
interventions to improve post-transplant medication compliance; 
improved treatment of depression in patients with diabetes or on 
dialysis; interventions targeted at increasing compliance in 
adolescents; development of interventions in the context of ethnicity, 
culture and SES; and studies of interactions between care providers and 
patients leading to improved adherence and outcome.

NATIONAL INSTITUTE ON DRUG ABUSE

NIDA is interested in research aimed at improving interventions that 
promote adherence to medication in individuals who are addicted to 
drugs (including but not limited to cocaine, nicotine, opiates, 
marijuana, prescription drugs, etc.). Of particular interest is 
research that integrates new developments in basic behavioral, 
cognitive, or clinical science to refine, test and improve the 
effectiveness of adherence interventions. Adherence to medication for 
drug addiction or adherence to medication for a co-morbid physical 
and/or mental health problem may be the focus of the research. A 
related announcement, delineating a “Stage Model” for behavioral 
intervention research, “Behavioral Therapies Development Program,” NIDA 
PA-99-107, can be found at 
http://grants.nih.gov/grants/guide/pa-files/PA-99-107.html.

NATIONAL INSTITUTE OF MENTAL HEALTH

NIMH is interested in expanding research on adherence and behavior 
change that integrates findings from the basic behavioral sciences with 
interventions for mental disorders, symptoms, or related disability. 
Included are studies of mechanisms and processes that enhance and/or 
interfere with adherence to preventive, pharmacological, psychosocial, 
and rehabilitative treatments. Potential research topics germane to 
adherence to interventions for mental disorders are listed in NIMH PA-
00-16 "Research on Adherence to Interventions for Mental Disorders" 
which can be can be found on the Web at 
http://www.nimh.nih.gov/grants/pamenu.htm. 

NATIONAL INSTITUTE OF NURSING RESEARCH

NINR is interested in research studies that involve nursing 
interventions or that have a direct impact on client adherence by a 
health team. NINR promotes research in health care and outcomes across 
all ages, in diverse populations, and for a wide variety of acute and 
chronic health conditions. NINR is interested in studies involving 
interventions to promote adherence behaviors. In addition to the client 
group, interventions may involve health care providers, family members, 
or other key individuals or groups involved in the process of promoting 
adherence. NINR encourages applications that include both 
pharmacological and other adherence interventions. 

REFERENCES

American Heart Association, The Multilevel Compliance Challenge: 
Recommendations for a Call to Action, Circulation, 1997; 95:1085-1090.
D. L. Roter, J. A. Hall, R. Merisca, B. Nordstrom, D. Cretin, and B. 
Svarstad, Effectiveness of interventions to improve patient compliance, 
Medical Care, 36, 8, 1998, pp. 1138-1161
Center for the Advancement of Health, Health Care Financing 
Administration, and National Institute on Aging, Interventions to 
Improve Adherence to Medical Regimens in the Elderly. Washington, DC: 
Center for Advancement of Health, 1999
R. B. Haynes, K. A. McKibbon, R. Kanani, M. C. Brouwers, and T. Oliver, 
Interventions for helping patients to follow prescriptions for 
medications, The Cochrane Library, 1999, Issue 1.
SPECIAL REQUIREMENTS

(a) DATA AND SAFETY MONITORING. A clinical trial entails a relationship 
between participants and investigators, both of whom must fulfill 
certain obligations for the effort to succeed. Participants must be 
fully informed of the study requirements throughout the conduct of the 
trial and should comply with the rigors of the research protocol or be 
allowed the opportunity to withdraw from participation. The 
investigators must protect the health and safety of participants, 
inform participants of information relevant to their continued 
participation, and pursue the research objectives with scientific 
diligence. In 1994, the NIH Office of Extramural Research established 
the Committee on Clinical Trial Monitoring to review the oversight and 
management practices of the ICs for phase III clinical trials. One of 
the outcomes of this Committee's review was a strong recommendation 
that "all trials, even those that pose little likelihood of harm, 
should consider an external monitoring body." 
Applicants should describe and budget for the organizational structures 
and procedures they will employ to ensure the safety of participants 
and the validity and integrity of the data. (For a statement of issues 
and concerns, see “NIH Policy for Data and Safety Monitoring,” NIH 
Guide to Grants and Contracts, Release Date: June 10, 1998, 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.) At the 
time of the award, applicants should be prepared to make adjustments to 
their procedures based upon the policies of the NIH Institute/Center 
administering their grant.

(b) SAMPLE SIZE/DATA ANALYSIS. Assumptions and steps used to arrive at 
the proposed sample size must be described. Discussion should be 
devoted to analytic features of the study including primary endpoint 
specification, statistical power estimates, randomization procedures, 
statistical methods, and use of the intention-to-treat principle (i.e. 
whether the primary analysis will be carried out based on the original 
treatment assignment versus treatment administered), as applicable.

(c) LEVERAGING. Applicants should consider taking advantage of other 
research projects (e.g., clinical trials about to be implemented) that 
could be expanded by adding a research component on adherence. Such 
projects might provide access to subject populations or settings as 
well as reduce the costs of conducting research.

(d) ANNUAL MEETINGS AND COLLABORATION. Successful applicants will be 
asked to participate in yearly meetings to report progress, discuss 
problems, and share information related to the conduct of their grants. 
Previous experience with such meetings has shown that they can provide 
opportunities for grantees to work collaboratively in various areas 
such as measurement of treatment fidelity and adherence, techniques for 
participant recruitment and retention, development and implementation 
of interventions, and data archiving and sharing. Cooperation across 
funded studies increases their value by facilitating the accumulation 
of comparable knowledge and experience. Applicants should include in 
their budget funds for two or three investigators to attend the annual 
collaborative meetings to be held in Bethesda, MD, at the NIH. The 
first of these meetings will be held in November or December 2000.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification is provided 
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 research involving human subjects should 
read the "NIH Guidelines For Inclusion of Women and Minorities as 
Subjects in Clinical Research," which have been published in the 
Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH 
Guide for Grants and Contracts, Volume23, Number 11, March 18, 1994.

Investigators also may obtain copies of the policy from the program 
staff listed under INQUIRIES. Program staff may also provide additional 
relevant information concerning the policy.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS 
IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH 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 
to exclude them. (See NIH Guide to Grants and Contracts, March 6, 1998 
or http://grants.nih.gov/grants/guide/notice-files/not98-024.html.) 

Investigators also may obtain copies of these policies from the program 
staff listed under INQUIRIES. Program staff may also provide additional 
relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 6, 2000, a letter 
of intent that includes a descriptive title of the proposed research, 
the name, address, and telephone number of the Principal Investigator, 
the identities of other key personnel (including research project 
collaborators and consultants) and participating institutions, and the 
number and title of this RFA. Although a letter of intent is not 
binding and does not enter into the review of a subsequent application, 
the information that it contains allows NIH staff to estimate the 
potential review workload and avoid conflict of interest in the review.

The letter of intent should be sent to:
Dr. Ronald P. Abeles
Office of Behavioral and Social Sciences Research
National Institutes of Health
Gateway Building, Rm. 2C234
7201 Wisconsin Ave., MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-7859
Fax: 301-435-8779
E-mail: Abeles@nih.gov

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) must be used in 
applying for these grants, with the modifications noted below. 
Applications kits are available at most institutional offices of 
sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge 
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-435-0714, E-
mail: GrantsInfo@nih.gov. Applications are also available on the World 
Wide Web at http://grants.nih.gov/grants/forms.htm.

The MODULAR GRANT concept establishes specific modules in which direct 
costs may be requested as well as a maximum level for requested 
budgets. Only limited budgetary information is required under this 
approach. The JUST-IN-TIME concept allows applicants to submit certain 
information only when there is a possibility for an award. It is 
anticipated that these changes will reduce the administrative burden 
for the applicants, reviewers and Institute staff. 

MODULAR GRANT applications request direct costs in $25,000 modules, up 
to a total direct cost request of $350,000 per year. For the purposes 
of this RFA, the usual maximum of $250,000 for modular awards does NOT 
apply. The total direct costs must be requested in accordance with the 
program guidelines and the modifications made to the standard PHS 398 
application instructions described below:
(a) PHS 398

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct 
Costs (in $25,000 increments up to a maximum of $350,000) and Total 
Costs [Modular Total Direct plus Facilities and Administrative (F&A) 
costs] for the initial budget period Items 8a and 8b should be 
completed indicating the Direct and Total Costs for the entire proposed 
period of support.

o  DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form 
Page 4 of the PHS 398. It is not required and will not be accepted with 
the application.

o  BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete 
the categorical budget table on Form Page 5 of the PHS 398. It is not 
required and will not be accepted with the application. 

Applications should include in their budgets funds for attending an 
annual meeting of research projects funded under this RFA. For 
budgeting purposes, applicants should assume that the meetings would be 
for two days in Bethesda, Maryland at the National Institutes of Health 
and require the attendance of two or three investigators per funded 
project. (See SPECIAL REQUIREMENTS, (d) ANNUAL MEETINGS AND 
COLABORATION.)

o  NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget 
Narrative page. (See 
http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages.) At the top of the page, enter the total direct costs requested 
for each year. This is not a Form page.

Under Personnel, List key project personnel, including their names, 
percent of effort, and roles on the project. No individual salary 
information should be provided. However, the applicant should use the 
NIH appropriation language salary cap and the NIH policy for graduate 
student compensation in developing the budget request.

For Consortium/Contractual costs, provide an estimate of total costs 
(direct plus facilities and administrative) for each year, each rounded 
to the nearest $1,000. List the individuals/organizations with whom 
consortium or contractual arrangements have been made, the percent 
effort of key personnel, and the role on the project. Indicate whether 
the collaborating institution is foreign or domestic. The total cost 
for a consortium/contractual arrangement is included in the overall 
requested modular direct cost amount. Include the Letter of Intent to 
establish a consortium.

Applicants are strongly encouraged to request the same number of 
modules for each year of funding. Provide an additional narrative 
budget justification for any variation in the number of modules 
requested.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information 
used by reviewers in the assessment of each individual's qualifications 
for a specific role in the proposed project, as well as to evaluate the 
overall qualifications of the research team. A biographical sketch is 
required for all key personnel, following the instructions below. No 
more than three pages may be used for each person. A sample 
biographical sketch may be viewed at 
http://grants.nih.gov/grants/funding/modular/modular.htm. 

- Complete the educational block at the top of the form page;
-  List position(s) and any honors;
-  Provide information, including overall goals and responsibilities, 
on research projects 
ongoing or completed during the last three years.
-  List selected peer-reviewed publications, with full citations;

o  CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate 
the type of agreement and the date. All appropriate exclusions must be 
applied in the calculation of the F&A costs for the initial budget 
period and all future budget years.
o  The applicant should provide the name and phone number of the 
individual to contact concerning fiscal and administrative issues if 
additional information is necessary following the initial review. 

(b) Mailing Procedures

The RFA label available in the PHS 398 (rev. 4/98) application form 
must be affixed to the bottom of the face page of the application. 
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 sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change.  Please note this is in pdf format.

Submit a signed, original of the application, including the Checklist, 
and four (4) signed photocopies of the application in one package to: 

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, send one (1) additional copies of the 
application to:

Dr. Ronald P. Abeles
Office of Behavioral and Social Sciences Research
National Institutes of Health
Gateway Building, Rm. 2C234
7201 Wisconsin Ave., MSC 9205
Bethesda, MD 20892-9205

It is important to send this copy at the same time that the original 
and four copies are sent to the Center for Scientific Review (CSR).

Applications must be received by April 6, 2000. 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by the participating NIH entities. Incomplete and 
nonresponsive applications will be returned to the applicant without 
further consideration. Applications that are complete and responsive to 
the RFA will be evaluated for scientific and technical merit by an 
appropriate peer review group convened by the CSR in accordance with 
the review criteria stated below. As part of the initial merit review, 
all applications will receive a written critique and may undergo a 
process in which only those applications deemed to have the highest 
scientific merit, generally the top half of applications under review, 
will be discussed, assigned a priority score, and receive a second 
level review by the appropriate national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. 
In the written comments reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals. Each of these criteria will be addressed and 
considered in assigning the overall score, weighting them as 
appropriate for each application. Note that 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.
In addition to the criteria list below, the initial review group will 
examine: the appropriateness of proposed project budget and duration; 
the adequacy of plans to include both genders, minorities (and their 
subgroups), and childen as appropriate for the scientific goals of the 
research, and plans for the recruitment and retention of subjects; the 
provisions for the protection of human and animal subjects; and the 
safety of the research environment.

(1)  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? For Pilot Research Projects, what is the 
likelihood that the research will contribute to the development of 
interdisciplinary programs or more mature research endeavors?

(2) 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? 

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

(4) INVESTIGATORS: Is each 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)? 

(5) ENVIRONMENT: Does the scientific environment in which the work 
will be done contribute to the probability of success of the project? 
Do the proposed studies take advantage of unique features of the 
scientific environment or employ useful collaborative arrangements?

AWARD CRITERIA

Applications will compete for available funds with all other approved 
applications submitted in response to this RFA. The following will be 
considered in making funding decisions:

The quality of the proposed project as determined by peer review

o  Availability of funds

o  The research priorities of the participating NIH Institutes.

INQUIRIES

Inquiries concerning this RFA are encouraged. The opportunity to 
clarify any issues or questions from potential applicants is welcome. 
Applicants may also subscribe to the OBSSR’s automated e-mail service 
in order to obtain subsequent information about this RFA. To subscribe, 
please send a message addressed to listserv@list.nih.gov. The message 
should read SUBscribe RFA-ADHERENCE-L [your full name]. The message is 
case sensitive; so capitalize as indicated! Do not include the 
brackets. For example, for Robin Smith to subscribe, the message would 
read “SUBscribe RFA-ADHERENCE-L Robin Smith” (omit the quotation 
marks). The subject line should be blank. Subscribers will receive a 
confirmation of their subscription along with instructions on how to 
use the LISTSERV and how to unsubscribe. Information concerning the 
RFA, including “Frequently Asked Questions and Answers,” will be posted 
on the OBSSR HomePage at http://www1.od.nih.gov/obssr/adherence.htm. 

(a) Direct GENERAL INQUIRIES to:

Dr. Ronald P. Abeles
Office of Behavioral and Social Sciences Research
National Institutes of Health
Gateway Building, Rm. 2C234
7201 Wisconsin Ave., MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-7859
Fax: 301-435-8779
E-mail: Abeles@nih.gov

(b) Direct inquiries regarding specific PROGRAMMATIC ISSUES to the 
staff of the appropriate Institute/Center:
Dr. Roy S. Wu
Grants Program Director
NCI
6130 Executive Blvd., EPN 734
Bethesda, MD 20892-7432
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Telephone: 301-496-8866
Fax: 301-480-4663
E-mail: rw51j@nih.gov 

Ms. Elizabeth J. Thomson
Program Director, Ethical, Legal, and Social Implications Research
NHGRI
National Institutes of Health
31 Center Drive, MSC 2033, Room B2B07
Bethesda, MD 20892-2033
Telephone: 301-402-4997
Fax: 301-402-1950
E-mail: et22s@nih.gov

Dr. Susan M. Czajkowski
Behavioral Medicine Research Group
NHLBI
Rockledge II, Rm. 8114
6701 Rockledge Dr. MSC 7938
Bethesda, MD 20892-7938
Telephone: 301-435-0406
Fax: 301-480-1773
E-mail: czajkows@nih.gov

Dr. Marcia G. Ory
Behavioral and Social Research
NIA
Gateway Building, Room 533
7201 Wisconsin Avenue MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-402-4156
Fax: 301-402-0051
E-mail: Marcia_Ory@nih.gov 

Dr. Margaret E. Mattson
Treatment Research Branch
Division of Clinical and Prevention Research
NIAAA
Willco Building MSC-7003
6000 Executive Blvd.
Bethesda MD 20892-7003
Telephone: 301-443-0796
Fax: 301-443-8774
E-mail: mmattson@willco.niaaa.nih.gov 

Dr. Julia B. Freeman
Centers Program, EP
NIAMS 
Natcher Building, Room 5AS.19F - MSC 6500
Bethesda, MD 20892-6500
Bethesda, MD 20814 (for express/courier service)
Telephone: 301-594-5052
Fax: 301-480-4543
E-mail: Julia_B_Freeman@nih.gov 

Dr. Lynne M. Haverkos
Child Development and Behavior Branch
NICHD
6100 Executive Boulevard, Room 4B05B, MSC 7510
Bethesda, MD 20892-7510
Telephone: 301-435-6881
Fax: 301-480-7773
E-mail: lh179r@nih.gov 

Dr. Patricia Bryant
Program Director, Behavioral and Health Promotion Research
Office of Clinical, Behavioral, and Health Promotion Research
NIDCR
Natcher Building, Rm 4AN24E
Bethesda, MD 20892-6402
Telephone: 301-594-2095
Fax: 301-480-8318
E-mail: BryantP@de45.nidr.nih.gov

Dr. Sanford Garfield
Senior Advisor for Biometry and Behavioral Research
NIDDK
Bldg. 45, Rm. 5AN24B
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone: 301-594-8803
Fax: 301-402-6271
E-mail: garfields@extra.niddk.nih.gov 

Dr. Lisa Onken
Behavioral Treatment Development Program
NIDA
6001 Executive Blvd., Room 4227, MSC 9541
Bethesda, MD 20892-9541
Telephone: 301-443-0107
Fax: 301-443-8674
E-mail: lonken@mail.nih.gov 

Dr. Robert K. Heinssen
Chief, Adherence and Behavior Change Research Program
Acting Chief, Psychotic Disorders Research Program
Division of Mental Disorders, Behavioral Research and AIDS 
NIMH
Room 6190, Mail Stop 9615
6001 Executive Blvd.
Bethesda, MD 20892-9615
Telephone: 301-435-0371
Fax: 301-443-4611
E-mail: rheinsse@mail.nih.gov 

Dr. Nell Armstrong
Program Director
NINR
Building 45, Room 3AN12
Bethesda MD 20892-6300
Telephone: 301-594-5973
Fax: 301-480-8260
E-mail: nell_armstrong@nih.gov 

(c) Direct inquiries regarding FISCAL MATTERS to the staff of the 
appropriate Institute/Center:

Ms. Eileen M. Natoli
Grants Administration Branch
NCI
6120 Executive Blvd.
EPS - 243
Rockville, Md. 20852
Telephone: 301-496-8791
Fax: 301-496-8601
natolie@gab.nci.nih.gov.

Ms. Jean M. Cahill
Chief Grants Management Officer
NHGRI
31 Center Drive Rm. B2B34
MSC 2031
Bethesda, MD 20892-2031
Telephone: 301-435-7858
Fax: 301-402-1951
E-mail: Jean_Cahill@NIH.GOV

Ms. Rhonda Mays
Grants Management Office
NHLBI
Rockledge II, Room 7138
6701 Rockledge Dr. MSC 7938
Bethesda, MD 20892-7938
Telephone: 301-435-0186
Fax :301-480-0422
E-mail: maysr@nih.gov.

Mr. Bob Pike
Grants and Contracts Management Office
NIA
Gateway Building, Suite 2N212
7201 Wisconsin Avenue MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-1472
Fax: 301-402-3672
E-mail: Bob_Pike@nih.gov 

Ms. Judy Simons
Grants Management Branch
NIAAA
Willco Building MSC-7003
6000 Executive Blvd
Bethesda MD 20892-7003
Telephone: 301-443-2434
Fax: 301-443-3891
E-mail: jsimons@willco.niaaa.nih.gov 

Ms. Sally A. Nichols 
Grants Management Officer
NIAMS
Natcher Building Room 5AS.49F - MSC 6500
Bethesda, MD 20892-6500
Telephone: 301-594-3535
Fax: 301-480-5450
E-mail: nicholss@exchange.nih.gov 

Mr. E. Douglas Shawver
Grants Management Branch
NICHD
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD 20892-7510
Telephone: 301-435-6999
Fax: 301-402-0915
E-mail: shawverd@exchange.nih.gov 

Mr. Martin Rubinstein
Office of Grants Management
NIDCR
Natcher Building, Rm 4AN-44A
Bethesda, MD 20892-6402
Telephone: 301-594-4800
Fax: 301-480-8301
E-mail: Martin.Rubinstein@nih.gov

Ms. Cheryl Chick 
NIDDK
Bldg. 45, Rm. 6AN-38J
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone: 301-594-8825
Fax: 301-480-4237
E-mail: chickc@extra.niddk.nih.gov

Mr. Gary Fleming
Grants Management Branch
NIDA
6001 Executive Blvd., Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone: 301-443-6710
Fax: 301-594-6847
E-mail: gf6s@nih.gov 

Ms. Diana S. Trunnell
Grants Management Branch
NIMH
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: 301-443-2805
Fax: 301-443-6885
E-mail: Diana_Trunnell@nih.gov 

Mr. Jeff Carow
Grants Management Office
NINR
Building 45, Room 3AN12
45 Center Drive, MSC 6301
Bethesda, MD 20892-6301
Telephone: 301-594-6869
Fax: 301-480-8260
E-mail: jeff_carow@nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
Nos. 93.395 (NCI), 93.172 (NHGRI), 93.937 (NHLBI), 93.866 (NIA), 93.891 
(NIAAA), 93.846 (NIAMS), 93.929 (NICHD), 93.121 (NIDCR), 93.279 (NIDA), 
93.847/848/849 (NIDDK), 93.859 (NIGMS), 93.242 (NIMH), and 93.361 
(NINR). Awards are made under authorization of the Public Health 
Service Act, Title IV, Part A (Public Law 78-410), as amended by Public 
Law 99-158, 42 USC 241 and 285) and administered under PHS grants 
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This 
program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to 
provide a smoke-free workplace and promote the non-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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