PRESCRIPTION DRUG ABUSE

RELEASE DATE:  June 16, 2004

PA NUMBER:  PA-04-110

December 8, 2006 - The R01 portion of this funding opportunity has been 
replaced by PA-07-123, which now uses the electronic SF424 (R&R) 
application for February 5, 2007 submission dates and beyond.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. 
Replacement R03 (PA-06-340) and R21 (PA-06-339) funding opportunity announcements have been issued for the submission date of June 1, 2006 and submission dates 
for AIDS and non-AIDS applications thereafter.

EXPIRATION DATE for R03 and R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R03 and R21 AIDS and AIDS-Related Applications: May 2, 2006 
Expiration Date for R01 Non-AIDS Applications: November 2, 2006 
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:  
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute on Drug Abuse (NIDA)
 (http://www.nida.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.279

THIS PROGRAM ANNOUNCEMNT (PA) CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanisms of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF PA

This PA supersedes PA-01-048, "Prescription Drug Abuse," issued on February 
12, 2001 in the NIH Guide for Grants and Contracts at 
http://grants.nih.gov/grants/guide/pa-files/PA-01-048.html.  In revising and 
reissuing this PA, NIDA continues to encourage research aimed at 
understanding and reducing prescription drug abuse while supporting 
appropriate medical use of therapeutic agents with abuse liability.  To 
promote the Nation’s health, research is needed to understand the factors 
contributing to prescription drug abuse, to characterize the adverse medical, 
behavioral, and social consequences associated with this abuse, and to 
develop effective prevention and service delivery approaches and behavioral 
and pharmacological treatments.  Applications to address this issue are 
encouraged across a broad range of experimental approaches including basic, 
clinical, epidemiological, prevention, and treatment studies.

RESEARCH OBJECTIVES  

Background

Prescription drug abuse is a major public health concern.  The 2002 National 
Survey on Drug Use and Health (formerly known as the National Household 
Survey on Drug Abuse) reports that 6.2 million Americans age 12 and older are 
current users of prescription drugs for nonmedical purposes.  An estimated 
4.4 million used pain relievers, 1.8 million used tranquilizers, 1.2 million 
used stimulants, and 0.4 million used sedatives.  Lifetime nonmedical pain 
reliever prevalence among youths aged 12 to 17 increased from 2001 (9.6%) to 
2002 (11.2%), continuing an increasing trend from 1989 (1.2%).  Among young 
adults aged 18 to 25, the rate increased from 19.4% in 2001 to 22.1% in 2002.  
The young adult rate had been 6.8% in 1992.  Lifetime nonmedical use of 
stimulants increased steadily from 1990 to 2002 for youths aged 12 to 17 (0.7 
to 4.3%). For young adults aged 18 to 25, rates declined from 1981 to 1994 
(from 10.9 to 5.9%), then increased to 10.8% in 2002.  Rates increased 
between 2001 and 2002 for both youths (3.8 to 4.3%) and young adults (10.2 to 
10.8%).

The number of new initiates to nonmedical pain reliever use increased from 
628,000 in 1990 to 2.7 million in 2000.  About half (52%) of the new users in 
2001 were females. In 2001, the number was 2.4 million, not significantly 
different from 2000. First use of stimulants increased during the 1990s from 
270,000 in 1991 to 983,000 in 2000 and 808,000 in 2001.  Initiation of 
tranquilizer use increased steadily during the 1990s, from 373,000 initiates 
in 1990 to 1.3 million in 2000 and 1.1 million in 2001.  The number of 
sedative initiates has remained below 300,000 per year since 1981.

Drug Abuse Warning Network (DAWN) data show that rates per 100,000 of 
emergency room mentions of narcotic analgesics/combinations (category 
consists of drugs containing narcotic analgesics alone as well as narcotics 
in combination with other drugs) have increased 138.7% from 1995 to 2002 and 
18.5% from 2001 to 2002.  In 2002, the Monitoring the Future study added new 
questions on the nonmedical use of Vicodin and OxyContin.  In both 2002 and 
2003, past year use of Vicodin® (hydrocodone) and OxyContin® (oxycodone 
hydrochloride) by 12th graders has been about 4% while past year use of 
Vicodin has been about 10%, raising serious concern about prescription opioid 
abuse among youth.

In addition, concerns have been raised about increasing substance abuse among 
older adults (age 60 and older) and the potential impact of the aging of the 
baby boom generation on the need for substance abuse treatment (Gfroerer et 
al., Drug Alcohol Depend. 69, 127-135, 2003).   Alcohol and prescription drug 
misuse may affect as many as 17% of older adults [Substance Abuse Among Older 
Adults, SAMHSA/CSAT Treatment Improvement Protocol (TIP) Series 26].  Yet, 
proper treatment of many medical conditions requires the use of medications 
that can be misused, abused, and/or lead to dependency.

Applications are sought to define the extent of the problem of prescription 
drug abuse, to characterize this problem in terms of class of drug abused, 
etiology of abuse, and populations most affected (including racial/ethnic 
minority and gender analyses).  Studies are needed on all classes of 
prescription drugs with abuse liability, including analgesics, stimulants, 
sedative/hypnotics, anxiolytics, and muscle building/performance enhancing 
drugs such as anabolic steroids.  Researchers are encouraged to study the 
relationship between the prescription medication, the indication for which 
the medication was prescribed (e.g., pain, sleep disorder, anxiety disorder, 
obesity), and the environmental and individual factors contributing to abuse.

Studies are also needed on the factors leading to diversion of prescription 
drugs into channels of illicit drug distribution and on measures to lessen 
this diversion, such as science-based education of health professionals.  The 
recent proliferation of internet sites offering controlled substances for 
sale without a prescription (Forman, JAMA, 290, 889, 2003) requires further 
investigation.  Research is needed to describe the populations most at risk 
for abuse of particular classes of drugs (including demographic factors and 
reasons for use), the social norms and social contexts associated with use, 
the source(s) of these drugs, and the consequences of drug use (e.g., adverse 
health outcomes such as drug overdose and drug interactions and behavioral 
and social consequences such as cognitive impairment, absenteeism, and 
accidents).  To reduce prescription drug abuse, research is needed on 
prevention approaches, service delivery, and behavioral and pharmaco- 
therapies targeted to particular populations (e.g., the elderly, women, 
adolescents, health professionals, and those with comorbid substance abuse 
and mental health disorders and/or medical disorders).

Clinical studies are needed that take into account the patient’s age, gender, 
race/ethnicity, medical and psychiatric diagnoses, and current symptomatology 
and past and present treatments, as well as the clinical appropriateness or 
inappropriateness of prescribing practices.  Clinical neurobiological 
investigations using a variety of brain imaging methods also can allow for a 
better understanding of how these prescription drugs affect brain processes 
and systems over the life span.  Studies are also necessary to determine how 
attitudes, knowledge, and patterns of prescribing vary across categories of 
patients and health care providers and how these contribute to inappropriate 
prescribing practices and disparities in health care.  For example, 
pharmacies may not stock opioid pain medications in racial and ethnic 
minority communities or low-income communities, and there may be disparities 
in physicians’ prescribing practices to minority and low socioeconomic status 
(SES) patients.  Conversely, women are much more likely than men to be 
prescribed abusable prescription drugs, and prescription drug misuse/abuse 
among older women is a serious problem that has received little attention and 
often goes unrecognized by health professionals (CASA Report, June 1998).

In general, prescription drug abuse in older adults begins with misuse due to 
inappropriate prescribing or lack of patient compliance with medication 
regimens.  Continued misuse may progress to abuse and dependence.  Older 
adults may be more vulnerable to prescription drug abuse because of age-
related physiological changes that may influence the metabolism and response 
to prescription drugs, greater likelihood of having undiagnosed psychiatric 
and medical comorbidities, and difficulties in compliance with complex 
multiple drug regimens that may increase the likelihood of drug interactions.  
For example, benzodiazepines are frequently prescribed to older adults, but 
age-related changes in drug metabolism, interactions with other prescription 
and over-the-counter medications, and use of alcohol may lead to increased 
use/misuse/abuse and adverse consequences such as impaired functional 
capacity and cognition.

Yet, older Americans, their families, and their health care and service 
providers are frequently uninformed about the potential problems with 
psychoactive prescription drugs and, therefore, do not recognize these 
problems when they occur.  The aging of the baby boom cohort may enhance the 
occurrence of substance abuse, including prescription drug abuse among older 
Americans because of this cohort’s prior use and abuse of psychoactive 
compounds.  There is a need for research to develop screening, assessment, 
and diagnostic instruments (especially for use by health professionals in 
primary care settings) and prevention and treatment approaches targeted to 
prescription drug misuse and abuse in older adults.

The increased use of prescription drugs among high school and college age 
youth is also of great concern.  In the 2003 Monitoring the Future study, 
among twelfth graders, annual prevalence of Vicodin® use was second only to 
marijuana use.  Young people frequently mix prescription drugs with other 
drugs of abuse, such as marijuana and alcohol, putting them at risk for drug 
interactions and overdose.  Prescription of methylphenidate and other 
stimulants to treat attention-deficit hyperactivity disorder (ADHD) has 
increased in recent years.  A new, stand-alone question on nonmedical 
Ritalin® (methylphenidate) use was added to the Monitoring the Future survey 
in 2001, (Secondary School Students, 2002).  Using this new question, annual 
prevalence rates among twelfth graders was 4.0%; about half (1.9%) reported 
using only once or twice in the past year, but 0.9% reported using 10 or more 
times during the year.  Studies are needed on the extent of misuse and abuse 
of prescribed stimulant medications and on the extent to which youth share 
prescribed stimulants with their peers.  There is also a need for 
developmentally appropriate therapies that can engage and retain adolescents 
in treatment for prescription drug abuse.

In addition, doctors, nurses, dentists, pharmacists, veterinarians, and other 
health professionals are at risk because of their ready access to 
prescription drugs with abuse liability.  Research is needed to identify the 
components of effective prevention and treatment approaches targeted toward 
health professionals.  Furthermore, while some health professionals may 
contribute to the misuse and abuse of prescription drugs because of 
inappropriate prescribing behaviors, others may provide inadequate 
pharmacotherapy for pain and other conditions because of fear that their 
patients will become addicted or that they will incur regulatory scrutiny.  
There is a need to develop and evaluate innovative science based education 
approaches for health professionals.  Best practices and training protocols 
for health care workers require research not only on approaches, but also on 
methods to transfer science into the field.

Program Description

A range of research is needed to combat prescription drug abuse--from 
specifying the extent and nature of the problem (including health, 
behavioral, and social consequences) to developing, evaluating, and 
disseminating effective prevention and treatment approaches.  Research is 
needed to identify addiction risk factors, including those associated with 
the chronic therapeutic use of analgesics, stimulants, and sedative-hypnotics 
for psychiatric and other medical illnesses.  Improved means of screening, 
assessing, and diagnosing those at high risk of abusing or becoming addicted 
to prescribed psychoactive medications are needed.  Research is needed to 
examine the interaction of patient behavior, social and physical environment, 
and medical and drug abuse treatment practice to improve prescribing, 
screening, referral, and treatment processes in the health care system.  
Treatment studies are needed to develop and evaluate behavioral therapies and 
combined behavioral and pharmaco-therapies for prescription drug abuse, with 
particular attention to populations at highest risk (adolescents, women, 
patients with comorbid psychiatric and/or physical illness, the elderly, and 
those with a history of polydrug abuse).  Basic preclinical and clinical 
research is needed to understand the neurobiological, behavioral, 
pharmacological, and genetic basis of prescription drug abuse.  Research is 
needed to identify interactions between abused prescription drugs and other 
abused drugs and alcohol.  Across levels of analysis and research domains, 
there is also an interest in stimulating development and integration of 
technologies (for example, from genetic, imaging, proteomic, metabolomic 
information and approaches) to observe and understand the etiology and 
biological and behavioral mechanisms associated with prescription drug abuse.

Areas of research interest include, but are not limited to, the following:

Epidemiology and Prevention Research

o Studies, by class of drug, on the nature and magnitude of prescription drug 
diversion from both licit and illicit sources.  Research to identify sources 
of illicit prescription drugs in different population subgroups.  Studies of 
the demographics of populations abusing each class of prescription drugs, 
including regional variations and rural-urban gradients.  Studies should 
consider the methodological aspects of measuring prescription drug abuse such 
as the nomenclature for prescription drugs used in various population groups 
and the accuracy of recall and reporting of medication names and dosing 
regimens.

o Research on the factors that influence temporal trends in abuse of 
prescription drugs such as changes in the health care system, prescriptive 
practices, and sources of prescription medications (local pharmacy, mail 
order, internet, other) and in the training of health care providers 
regarding prescribing medications with abuse liability.

o Studies on the role of the internet as both a source of prescription drugs 
and a source of information about these drugs.  Studies on the role of the 
internet and direct-to-consumer advertising in shaping attitudes and in 
influencing beliefs about the risks associated with prescription drugs.

o Studies to identify patient populations who are under- or over-medicated or 
have difficulty obtaining adequate treatment with controlled substances.  
Studies on prescribing practices and attitudes of physicians (by specialty 
area, including primary care physicians) toward prescribing medications with 
abuse liability to different patient populations (such as children and 
adolescents, women, the elderly, racial/ethnic minorities, uninsured) and 
patients with current or past substance abuse problems.

o Studies to evaluate whether prolonged treatment with prescription 
psychoactive drugs for conditions such as ADD/ADHD, sleep disorders, pain, 
obesity, anxiety disorders, etc. contributes to drug abuse or relapse to drug 
abuse in vulnerable individuals.

o Studies to evaluate whether noncompliance with prescription drug dosing 
increases the likelihood of transition from misuse to abuse, possibly by 
inducing sensitization.

o Studies to determine how prescription drug misuse and abuse, particularly 
by pregnant women, children, and adolescents, might increase the risk of 
abuse/addiction of illicit drugs over the life span.

o Studies of the factors that predispose an individual to over-rely on and to 
misuse psychoactive prescription and over-the-counter drugs (e.g., health 
beliefs and practices, health promotion behaviors, reliance on media, family 
and cultural practices).

o Studies of the adverse behavioral and social consequences associated with 
prescription drug misuse, abuse, and dependence, such as impairment in school 
performance, driving, parenting, job performance, independent living for the 
elderly, etc.

o Studies to determine incidence and prevalence of medical and health 
consequences of prescription drug misuse and abuse.  Of particular interest 
are studies in those with HIV/AIDS, hepatitis, and other infectious diseases 
that are prevalent in drug abusers.

o Studies to identify, design, and  evaluate prevention interventions for 
those adolescents and college-age youth at increased risk for prescription 
drug misuse and abuse.  Types of prescription misuse and abuse among youth 
include: 1) the mixing of prescription drugs with other drugs of abuse (e.g., 
marijuana, alcohol), which places them at risk for drug interactions and 
overdose; 2) misuse and abuse of prescribed stimulants and providing these 
drugs to their peers; 3) abuse of dextromethorphan (DXM), an over-the-counter 
drug, alone and in combination with other drugs of abuse; 4) use of 
stimulants on college campuses for appetite suppression, wakefulness, 
increased attention, and euphoria.

o Studies to design and evaluate prevention interventions for individuals who 
may be at increased risk for prescription misuse and abuse in the following 
populations: 1) individuals with illnesses, such as arthritis, back pain, 
insomnia, fatigue, obesity, anxiety, eating disorders, etc., who are 
prescribed abusable prescription drugs; 2) health care professionals; and 3) 
the elderly.

o Studies that theoretically and empirically explore the impact of existing 
evidence-based drug abuse prevention approaches, or variants of existing 
approaches, on  prescription drug abuse patterns.

Basic Preclinical and Clinical Research

o Employ basic studies using animal models to probe the effects of 
prescription drugs on neurobiological, neurochemical, and neurobehavioral 
processes.

o Study possible associations between physical dependence, produced by either 
medical or nonmedical prescription drug use, and the development of 
addiction. 

o Study the pharmacokinetics, pharmacodynamics, and pharmacogenetics of drug-
drug interactions between abused prescription drugs and other illicit drugs, 
as well as between prescription drugs and dietary supplements and drugs for 
treatment of infections (e.g., antiretrovirals). 

o Conduct pharmacogenetic studies examining the genetic variation in 
physiological homeostasis, neurocognitive processes, biological systems 
and/or metabolic effects of prescription drugs and vulnerability to 
addiction.

o Conduct studies to determine the health consequences of prescription drug 
abuse and their underlying pathophysiology in diverse populations, e.g., 
those with HIV/AIDS and other infectious diseases, adolescents, the elderly, 
women.  Consequences may include developmental, psychiatric, metabolic 
(including nutritional), endocrine, pharmacokinetic/pharmacodynamic drug-drug 
interactions, or other physiological system effects caused by, or associated 
with the abuse of prescription drugs.

o Research is needed to determine the extent and mechanisms by which abused 
prescription drugs affect neurobiological mechanism and behavioral processes 
during development (including prenatal exposure), adolescence and adulthood, 
including older adulthood.

o Determine how prescription drug abuse has a differential effect on brain 
processes across adulthood, particularly in elderly populations.  For 
example, what are the effects of prescription drugs on normal aging processes 
in the brain, and do they place individuals at increased risk (or earlier 
expression) of neurodegenerative diseases such as Parkinson’s disease, 
Alzheimer’s disease, and other neurocognitive disorders?

o Assess the risk of addiction to prescribed medications as a function of the 
medical condition for which the drug is prescribed. For example, is the risk 
of addiction to opioids lessened as a function of the degree of pain present? 
If so, the mechanism responsible for this variation needs to be examined.

o Cross-sensitization and relapse.  In animal models determine if exposure to 
prescription drugs can precipitate relapse or lead to cross-sensitization to 
other drugs.  

o Determine the  mechanism responsible for feelings of well-being induced by 
certain steroids (e.g., prednisone).  Is the euphoria sufficient to maintain 
drug-seeking?  Do steroids stimulate relapse under, for example, conditions 
of psychomotor stimulant abstinence?  Determine if steroids reduce the 
aversive effects of drug withdrawal.

o Assess whether prescription drugs affect the toxicity of other abused 
substances.  For example, fluoxetine is used in the treatment of depression 
and obsessive-compulsive disorder (OCD), but it is being misused/abused in an 
attempt to protect from the neurotoxic action of methamphetamine, ecstasy, 
and other "club drugs."  Studies are needed to determine the consequences of 
these drug combinations on neural mechanisms and behavioral.

o Study the acute and chronic interactions between prescription drugs and 
illicit substances at the behavioral and cognitive level of analysis.  Most 
notably, what are reinforcing characteristics of drug combinations?

o Develop and apply interoperable and scalable analytic, modeling and other 
computation and information tools (such as  those for dynamic semantic 
profiling, social and other network analysis, and data integration and 
management) to enable pattern recognition and analysis to facilitate 
understanding of emerging patterns of use, vulnerabilities, drug use and 
disease relationships, economic relationships, and other factors related to 
prescription drug abuse.

Treatment and Services Research

o Research on the development and testing of effective and comprehensive 
treatment approaches that may include behavioral, pharmacological, 
alternative or complementary therapies for individuals who abuse or become 
dependent on prescription analgesics, stimulants, anxiolytics, or sedative-
hypnotics.   Behavioral treatment and combined behavioral and pharmacological 
studies should be informed by the stage model of therapy development, 
described in detail in the Behavioral Therapies Development Program 
Announcement (http://grants.nih.gov/grants/guide/pa-files/PA-03-126.html).  
Treatment studies are encouraged to include tests of the mediators, 
moderators, key ingredients, and/or mechanisms of action at all stages of 
therapy development.

o Studies to develop and evaluate treatment approaches that maintain 
abstinence from prescription drug abuse and prevent relapse.

o Studies of brief behavioral treatment interventions for prescription drug 
misuse and abuse in primary care settings.

o Studies to develop and test age-appropriate, gender-sensitive, and 
culturally-relevant treatment approaches for prescription drug abusing 
individuals.

o Studies to adapt existing treatments for other drugs of abuse, or for other 
conditions, for use with individuals who abuse prescription drugs.

o Studies to develop and evaluate new and innovative therapies to treat 
prescription drug abuse that are based on promising findings from basic 
behavioral and cognitive research.

o Studies to develop and test, or to adapt, developmentally-appropriate 
behavioral treatments for adolescents who abuse prescription drugs, with 
particular attention to the types and patterns of drug use among adolescents 
and the challenges to engaging adolescents in treatment.

o Studies to develop and evaluate therapies  for individuals who abuse 
prescription drugs and have comorbid mental disorders, such as depression, 
anxiety disorders, post-traumatic stress disorder, and eating disorders or 
comorbid physical disorders such as sickle cell anemia, HIV/AIDS, 
musculoskeletal disease, etc. associated with chronic pain.

o Studies which utilize e-health tools such as computers and portable digital 
and wireless devices to improve access to treatment for prescription drug 
abuse and/or augment provision of treatment by health care providers.

o Studies to develop and evaluate effective treatment approaches for the 
management of pain, anxiety, sleep disorders, obesity etc., in substance 
abusing patients and people with a history of substance abuse.  Therapies are 
needed for patients who are self-medicating in an attempt to manage comorbid 
medical and/or psychiatric problems.

o Studies to develop and evaluate behavioral treatments to improve medication 
adherence and prevent misuse of prescribed medications among substance 
abusing patients with comorbid medical illnesses or mental disorders.

o Research on effective detoxification strategies for various classes of 
prescribed drugs with abuse liability.

o Pharmacotherapy studies to evaluate the use of medications for new 
indications in the treatment of prescription drug abuse (e.g., buprenorphine 
for oxycodone abuse).

o Studies to improve the screening, assessment, and recognition of 
prescription drug misuse, abuse, and dependence among patients being treated 
in health care settings for medical and/or psychiatric illnesses, especially 
those which are chronic in nature.

o Studies to improve the recognition and referral for intervention of 
employee prescription drug misuse and abuse in the workplace to ensure timely 
and appropriate referral for treatment. Research is needed on educational 
approaches to increase workforce awareness of prescription drug misuse and 
abuse.

o Studies to determine the factors that may affect access to treatment for 
prescription drug abuse and addiction, including treatment entry, readiness 
for treatment, retention in treatment, compliance with treatment, and 
treatment outcomes among prescription drug abusing women, adolescents, older 
adults, and racial/ethnic minorities.

o Studies to identify organizational characteristics (e.g., climate, culture, 
age, and size), financing, and managerial approaches to providing the most 
accessible and effective treatment for prescription drug abuse and addiction, 
including factors that enhance motivation to participate and remain in 
treatment, compliance with treatment, and relapse avoidance.  Research to 
identify the value added by linkages to relevant treatment services such as 
psychiatric, wellness, and social services is also welcome.

o Research to develop and evaluate effective strategies/approaches for 
disseminating science-based information on the recognition, prevention, and 
treatment of prescription drug abuse to health professionals and community-
based health care providers.  Research to determine the most effective 
approaches for enhancing utilization of science-based information and whether 
these approaches actually change practice behaviors.

o Research to develop and evaluate innovative health professional 
prescription drug education programs using new technologies, e.g. palm pilot, 
interactive computer based programs, virtual reality, etc.
 
o Research in pharmacoeconomics to study optimum drug therapy and health 
outcomes utilizing quality-of-life assessment and outcomes research.  Such 
studies would provide economic information to inform clinical prescribing 
decisions and allocation of healthcare resources.

MECHANISMS OF SUPPORT 

This PA will use the NIH research project (R01), small research grant (R03) 
(PA-03-108: NIH SMALL RESEARCH GRANT PROGRAM (R03), and 
exploratory/developmental research grant (R21) PA-03-107: NIH 
EXPLORATORY/DEVELOPMENTAL RESEARCH GRANT AWARD (R21) award mechanisms.  As an  
applicant you will be solely responsible for planning, directing, and 
executing the proposed project.  

This PA uses just-in-time concepts.  It also uses the modular budgeting as 
well as the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.  

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 institutions/organizations
o Faith-based or community-based organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Dorynne Czechowicz, M.D.
Division of Clinical Neurobiology, Development and Behavioral Treatment
National Institute on Drug Abuse, NIH, DHHS
6001 Executive Boulevard, Room 4231, MSC 9551
Bethesda, Maryland 20892-9551
Rockville, Maryland 20852 (for express/courier service)
Telephone: (301) 443-2237
Fax: (301) 443-8674
E-mail: dc97d@nih.gov

Lynda Erinoff, Ph.D.
Division of Epidemiology, Services and Prevention Research
National Institute on Drug Abuse, NIH, DHHS
6001 Executive Blvd., Room 5153 MSC 9589
Bethesda, MD 20892-9589
Rockville, Maryland 20852 (for express/courier service)
Telephone: 301-402-1972
Fax: 301-480-2543
E-mail: le30q@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
6101 Executive Boulevard, Suite 270, MSC 8403
Bethesda, MD  20892-8403
Telephone:  (301) 443-6710
FAX:  (301) 594-6849
E-mail:  gf6s@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html 
in an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

The title and number of this program announcement must be typed on line 2 of 
the face page of the application form and the YES box must be checked.

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

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular budget grant format.  The modular budget grant format simplifies the 
preparation of the budget in these applications by limiting the level of 
budgetary detail.  Applicants request direct costs in $25,000 modules.  
Section C of the research grant application instructions for the PHS 398 
(rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html 
includes step-by-step guidance for preparing modular grants.  Additional 
information on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:
   
1) Contact 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 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 IC staff member  
who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

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

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

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR will 
not accept any application in response to this PA that is essentially the 
same as one currently pending initial review unless the applicant withdraws 
the pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an unfunded version 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 weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.   Appropriate scientific review groups 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o 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 written critique
o Receive a second level review by an appropriate national advisory council 
or board. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review 
group will address and consider each of the following criteria in assigning 
the application’s overall score, weighting them as appropriate for each 
application.

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

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

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below)
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. 

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on Humane Care 
and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA 
Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

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. 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy, 
effectiveness and comparative trials (phase III). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.    (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a 
plan for data sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing.  Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. 

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, 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 
http://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 
http://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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information”, 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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 http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.

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)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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