Part I Overview Information

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Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov)

Title: Prescription Drug Misuse (R21)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue of PA-06-339.

Update: The following update relating to this announcement has been issued:

• November 2, 2012 - This PA has been reissued as PA-13-016.
• December 18, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.
• November 27, 2009 - See Notice NOT-MH-10-006 NIMH Announces Changes in NIMH Participation, As of January 8, 2010, NIMH will terminate or withdraw its participation from this FOA.
• August 26, 2009 - See Notice NOT-DA-09-011 Notice of Amendment to this PA.

Program Announcement (PA) Number: PA-08-128

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.279, 93.242

Key Dates
Release/Posted Date: April 3, 2008
Opening Date: May 16, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not required
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: May 8, 2011

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute on Drug Abuse and the National Institute of Mental Health invites research applications to reduce prescription drug misuse while supporting the appropriate medical use of therapeutic agents that carry an abuse liability. A range of research is being solicited to combat prescription drug misusefrom epidemiologic research specifying the extent and nature of the problem (including health and social consequences) as it relates to each specific drug and identifying determinants and trajectories of use. Basic science applications to determine mechanisms of action at the cellular level and possible mechanisms or medications to block or lessen the abuse potential are encouraged, as are health services applications with the goal of discovering effective clinical practices that identify those at risk and designing and disseminating prevention and treatment interventions.
• Mechanism of Support. This FOA will use the NIH Exploratory/Developmental (R21) grant mechanism and runs in parallel with a FOA of identical scientific scope, PA-08-127, that encourages applications under the R01 and PA-08-129 that encourages applications under the R03 mechanism.
• Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism, numbers, quality, duration, and costs of the applications received.
• Budget and Project Period. The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. The R21 is not renewable.
• Research Plan Component length: Item 3 of the Research Plan of the R21 application may not exceed 6 pages, including tables, graphs, figures, diagrams, and charts. For information on NIH Exploratory/Developmental Research Grant Award (R21) seehttp://grants1.nih.gov/grants/funding/funding_program.htm.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Include Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization 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 support.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
• Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement).
• Renewals. Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation) applications will not be accepted.
• Application Materials. See Section IV.1 for application materials.
  All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.
• General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
  • SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
  • General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose:

This Funding Opportunity Announcement (FOA) issued by the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH), National Institutes of Health (NIH), encourages research aimed at reducing prescription drug misuse while supporting appropriate medical use of therapeutic agents with abuse liability. To promote the Nations health, research is needed to understand the factors contributing to prescription drug abuse, to characterize the adverse medical 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, and economic studies.

Background:

Prescription drug abuse is a major public health concern. The 2006 National Survey on Drug Use and Health (NSDUH) published by the Substance Abuse and Mental Health Services Administration reports an estimated 7.0 million persons age 12 and over or 2.8 percent of the United States population were current (last month) nonmedical users of prescription-type psychotherapeutic drugs. Of these, 2 million used pain relievers in 2006, an increase from 4.7 million in 2005. 1.4 million used tranquilizers and 1.0 million used stimulants. From 2005 to 2006, the rate of past month nonmedical use of prescription-type psychotherapeutic drugs increased from 2.8 to 3.2 percent among males aged 12 or older, mirroring an increase in the nonmedical use of pain relievers (from 2.1 to 2.5 percent).

Of particular concern is that 2.6 million persons aged 12 or older used psychotherapeutics nonmedically for the first time within the past year. The numbers of new users of specific psychotherapeutics in 2006 were 2.2 million for pain relievers, 1.1 million for tranquilizers, and 845,000 for stimulants. More persons age 12 and over initiated misuse of pain relievers (2.2 million) than any other illicit substance. By comparison, 2.1 million started using marijuana in the year prior to the interview.

Reports from the Drug Abuse Warning Network show approximately 598,542 visits to emergency departments during 2005 involved the non-medical use of prescription drugs or over-the-counter medications with the majority involving multiple drugs (Drug Abuse Warning Network, 2005).

Prescription drug misuse is a growing problem for the baby boom cohort whose lifetime rates of illicit drug use are higher than those of older cohorts and are now developing many chronic age-related conditions. Alcohol and prescription drugmisuse may affect as many as 17% of older adults according to SAMHSA reports. In addition, proper treatment of many medical conditions requires the use of medicationsthat can be misused, abused, and/or lead to dependency. As a result, concerns have been raised about increasing substance abuse amongolder adults (age 60 and older) and the need for substance abuse treatmentResearch studying the specific treatment needs of this population, as well as treatment of those with chronic medical conditions and prescription drug misuse, ex. chronic pain and opioid misuse are responsive to this FOA. Another research priority is the need for a large scale randomized controlled study to determine the most effective way to treat chronic non-cancer pain with opioid medication.

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.Research studying the effect of new methods to control prescription misuse such as prescription monitoring programs is needed. 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., adversehealth outcomes such as drug overdose and drug interactions and behavioral and social consequences such as cognitive impairment, absenteeism, andaccidents). 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 should take into account the patients age, gender, race/ethnicity, medical and psychiatric diagnoses and current symptomatology,and past and present treatments, as well as the clinical appropriateness orinappropriateness of prescribing practices. Clinical neurobiologicalinvestigations using a variety of brain imaging methods also can allow for abetter understanding of how these prescription drugs affect brain processesand systems over the life span. Studies are also necessary to determine howattitudes, knowledge, and patterns of prescribing vary across categories ofpatients 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.

In general, prescription drug abuse in older adults begins with misuse due toinappropriate prescribing or lack of patient compliance with medicationregimens. 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 increaseduse/misuse/abuse and adverse consequences such as impaired functionalcapacity and cognition.

There is a need for research to develop new, and further validate existing 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 adults including the elderly.

The increased use of prescription drugs among high school and college ageyouth remains a great concern. In addition to the high prevalence of prescription opioids noted above, stimulant use is a growing concern. Prescription of methylphenidate and other stimulants to treat attention-deficit hyperactivity disorder (ADHD) has increased in recent years. Studies are needed on the extent of misuse and abuse of prescribed stimulant medications the reasons for misuse, 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 otherhealth 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.The impact of professional monitoring organizations on recovery and ability to insure safe practice standards is of interest, especially with the growing movement to eliminate these programs.

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. Evidence-based practices and training protocols for health care workers require research not only on the most effective approach, but also the most effective methods to disseminate new science into the field.

Program Description

A range of research is needed to combat prescription drug abuse--fromspecifying the extent and nature of the problem (including health,behavioral, and social consequences) to developing, evaluating, anddisseminating 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, andthose 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 oftechnologies (for example, from genetic, imaging, proteomic, metabolic 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

• 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 dosingregimens.
• 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.
• 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 theInternet and direct-to-consumer advertising in shaping attitudes and ininfluencing beliefs about the risks associated with prescription drugs.
• 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.
• Studies to evaluate whether prolonged treatment with prescriptionpsychoactive drugs for conditions such as ADD/ADHD, sleep disorders, pain,obesity, anxiety disorders, etc. contributes to drug abuse or relapse to drugabuse in vulnerable individuals.
• Studies to evaluate whether noncompliance with prescription drug dosingincreases the likelihood of transition from misuse to abuse, possibly byinducing sensitization.
• Studies to determine how prescription drug misuse and abuse, particularlyby pregnant women, children, and adolescents, might increase the risk ofabuse/addiction of illicit drugs over the life span.
• Studies of the factors that predispose an individual to over-rely on and tomisuse psychoactive prescription and over-the-counter drugs (e.g., healthbeliefs and practices, health promotion behaviors, reliance on media, familyand cultural practices).
• Studies of the adverse behavioral, social and economic consequences associated with prescription drug misuse, abuse, and dependence, such as impairment in school performance, driving, parenting, job performance, independent living for theelderly, etc.
• Studies to determine incidence and prevalence of medical and healthconsequences of prescription drug misuse and abuse. Of particular interestare studies in those with HIV/AIDS, hepatitis, and other infectious diseasesthat are prevalent in drug abusers.
• Studies to identify, design, and evaluate prevention interventions forthose adolescents and college-age youth at increased risk for prescriptiondrug 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.
• 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.
• Studies that theoretically and empirically explore the impact of existingevidence-based drug abuse prevention approaches, or variants of existingapproaches, onprescription drug abuse patterns.

Basic Preclinical and Clinical Research

• Employ basic studies using animal models to probe the effects ofprescription drugs on neurobiological, neurochemical, and neurobehavioralprocesses.
• Study possible associations between physical dependence, produced by either medical or nonmedical prescription drug use, or the development of addiction.
• 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).
• Conduct pharmacogenetic studies examining the genetic variation inphysiological homeostasis, neurocognitive processes, biological systems and/or metabolic effects of prescription drugs and vulnerability to addiction.
• 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.
• 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.
• Determine how prescription drug abuse has a differential effect on brainprocesses across adulthood, particularly in elderly populations. For example, what are the effects of prescription drugs on normal aging processesin the brain, and do they place individuals at increased risk (or earlier expression) of neurodegenerative diseases such as Parkinsons disease, Alzheimers disease, and other neurocognitive disorders?
• Assess the risk of addiction to prescribed medications as a function of themedical condition for which the drug is prescribed. For example, is the riskof 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.
• The effect of opioid hyperalgesia on the effectiveness of opioid medications and the relationship to tolerance and addiction.
• Cross-sensitization and relapse. In animal models determine if exposure to prescription drugs can precipitate relapse or lead to cross-sensitization to other drugs.
• 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.
• Assess whether prescription drugs affect the toxicity of other abusedsubstances. 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.
• Study the acute and chronic interactions between prescription drugs andillicit substances at the behavioral and cognitive level of analysis. Mostnotably, what are reinforcing characteristics of drug combinations?
• 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 andmanagement) to enable pattern recognition and analysis to facilitateunderstanding of emerging patterns of use, vulnerabilities, drug use anddisease relationships, economic relationships, and other factors related toprescription drug abuse.

Treatment and Services Research

• Research on the development, testing, and economic evaluation 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 and Integrative Treatment Development Program Announcement’s (R01: (http://grants.nih.gov/grants/guide/pa-files/PA-06-486.html; R21: http://grants.nih.gov/grants/guide/pa-files/PA-06-487.html; and R03: http://grants.nih.gov/grants/guide/pa-files/PA-06-488.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.
• Studies to develop and evaluate treatment approaches that maintainabstinence from prescription drug abuse and prevent relapse.
• Studies of brief behavioral treatment interventions for prescription drugmisuse and abuse in primary care settings.
• Studies to develop, test, and economically evaluate age-appropriate, gender-sensitive, andculturally-relevant treatment approaches for prescription drug abusingindividuals.
• Studies to adapt existing treatments for other drugs of abuse, or for otherconditions, for use with individuals who abuse prescription drugs.
• Studies to develop and evaluate new and innovative therapies to treatprescription drug abuse that are based on promising findings from basicbehavioral and cognitive research.
• Studies to develop and test, or to adapt, developmentally-appropriatebehavioral treatments for adolescents who abuse prescription drugs, withparticular attention to the types and patterns of drug use among adolescentsand the challenges to engaging adolescents in treatment.
• Studies to develop and evaluate therapies for individuals who abuseprescription drugs and have comorbid mental disorders, such as depression,anxiety disorders, post-traumatic stress disorder, and eating disorders orcomorbid physical disorders such as sickle cell anemia, HIV/AIDS,musculoskeletal disease, etc. associated with chronic pain.
• Studies which utilize e-health tools such as computers and portable digitaland wireless devices to improve access to treatment for prescription drugabuse and/or augment provision of treatment by health care providers.
• 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.
• 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.
• Research on effective detoxification strategies for various classes ofprescribed drugs with abuse liability.
• Pharmacotherapy studies to evaluate the use of medications for newindications in the treatment of prescription drug abuse (e.g., buprenorphinefor oxycodone abuse).
• Studies to improve the screening, assessment, and recognition ofprescription drug misuse, abuse, and dependence among patients being treatedin health care settings for medical and/or psychiatric illnesses, especiallythose which are chronic in nature.
• Studies to improve the recognition and referral for intervention ofemployee 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.
• 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.
• Studies to identify organizational characteristics (e.g., climate, culture,age, and size), financing, and managerial approaches to providing the mostaccessible and effective treatment for prescription drug abuse and addiction,including factors that enhance motivation to participate and remain intreatment, 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.
• Research to develop and evaluate effective strategies/approaches fordisseminating science-based information on the recognition, prevention, andtreatment 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.
• Research to develop and evaluate innovative health professionalprescription drug education programs using new technologies, e.g. palm pilot,interactive computer based programs, virtual reality, etc.
• Research in pharmaco-economics 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.

NIMH Areas of Interest:

Increased understanding of prescription drug abuse and its adverse consequences on mental health is of great interest to NIMH. The use of benzodiazepines is primarily to treat mental disorders and further basic science research on the mechanism of action of benzodiazepines may lead to efficacious treatments for anxiety that do not have significant drug abuse potential. It is also of great interest to NIMH to support research grant application in advancing knowledge that will reduce the burden of suicidality. The increase in the diversion of prescription drugs (especially opioids) among the nation's youth may play a role in both accidental and intentional overdose that can lead to medical morbidity or mortality among this vulnerable population.

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. 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 Web site at http://www.nida.nih.gov/about/organization/nacda/CouncilStatement.html.

The evolution and vitality of the biomedical sciences require a constant infusion of new ideas, techniques, and points of view.These may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data.By using the R21 mechanism, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research.

The R21 mechanism is intended to encourage new exploratory and developmental research projects. For example, such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area.These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism.For example, long-term projects, or projects designed to increase knowledge in a well-established area, will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel.These studies should break new ground or extend previous discoveries toward new directions or applications.Projects of limited cost or scope that use widely accepted approaches and methods within well established fields are better suited for the R03 small grant mechanism.Information on the R03 program can be found at http://grants.nih.gov/grants/funding/r03.htm.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

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1. Mechanism of Support

This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 3.4, Modular Budget Component, of the Application Guide).

All Foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

(You must select all categories that apply. Bulleted items may be included or excluded but not changed. Make sure this list is the same as that included in the Executive Summary.)

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization 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 support.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model.Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically.Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation) applications will not be accepted.

Applicants may submit a resubmission, but such application must include an Introduction addressing issues raised in the previous critique (Summary Statement).

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

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To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/applicants/get_registered.jsp) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered.

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual(s) designated as PDs/PIs on the application must be registered also in the NIH eRA Commons.In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
• Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an NIH Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
• When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization.PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
• This registration/affiliation must be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PIs assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., Special Instructions, regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic [non-U.S.] Entities)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

• Request budgets in U.S. dollars;
• Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component)(see NOT-OD-06-096);
• Not include any charge-back of customs and import fees;
• Comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF;
• If appropriate, request funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) ( see NOT-OD-01-028, March 29, 2001);
• Comply with Federal/NIH policies on human subjects, animals, and biohazards; and
• Comply with Federal/NIH biosafety and biosecurity regulations (see Section VI.2., Administrative and National Policy Requirements)

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 13 of the SF424 (R&R) Cover component.All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI.Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission.The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component.Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts.The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component.All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form.See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only.Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 3.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date:May 16, 2008 (Earliest date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): Not required.
Application Due Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time(of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

• If everything is acceptable, no further action is necessary. The application will automatically move forward to the Division of Receipt and Referral in the Center for Scientific Review for processing after two weekdays, excluding Federal holidays.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if it is determined that some part of the application was lost or did not transfer correctly during the submission process, the AOR/SO will have the option to Reject the application and submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to ensure that the issues are addressed and corrected. Once rejected, applicants should follow the instructions for correcting errors in Section 2.12, including the requirement for cover letters on late applications. The Reject feature should also be used if you determine that warnings are applicable to your application and need to be addressed now. Remember, warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two weekdays if no action is taken. Some warnings may need to be addressed later in the process.
• If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or did not transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Registration FAQs Important Tips -- Electronic Submission of Grant Applications.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide (MS Word or PDF) are to be followed, incorporating "Just-in-Time" information concepts, and with the following requirements for R21 applications:

• R21 applications will use the modular as well as the non-modular budget formats and "Just-in-Time" information concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 two-year period. No more than $200,000 in direct costs will be allowed in any single year. All Foreign applicants must complete and submit budget requests using the Research & Related Budget component.
• Item 3 of the Research Plan of the R21 application may not exceed 6 pages, including tables, graphs, figures, diagrams, and charts.
• Introduction (required for a resubmission application) is limited to one page.
• Preliminary data are not required but may be included if available.
• Renewal (formerly competing continuation or Type 2) applications are not permitted.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the required page limitations may be delayed in the review process.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Indicate how the proposed project has specific relevance to the mission and objectives of the IC and has the potential for significantly advancing the health sciences in the United States.

Resource Sharing Plan(s)

Not applicable.

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(a) Data Sharing Plan: Not Applicable

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Section V. Application Review Information

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1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established Public Health Service (PHS) referral guidelines.

Applications that are complete will be evaluated for scientific and technical merit by (an) appropriate scientific review group(s) in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/) using the review criteria stated below.

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

• 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 rating;
• Receive a written critique; and
• Receive a second level of review by review by the appropriate national advisory council or board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

The NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research.

Because the Research Strategy is limited to 6 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria 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 an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious impact/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.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

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Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications from Foreign Organizations. Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

2.C. Resource Sharing Plan(s)

Not applicable.

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or impact/priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

• Data Sharing Plan. Not Applicable
• Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

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1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his/her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

For general inquiries and services research:

Richard A. Denisco M.D., M.P.H.
Division of Epidemiology, Services and Prevention Research
National Institute on Drug Abuse, NIH. DHHS
6001 Executive Boulevard, Room 5193
Bethesda, Maryland 20892
Telephone: 301-594-4371
E-mail: [email protected]

For basic science research:

Dave Thomas, Ph.D.
Division of Basic Neuroscience and Behavioral Research
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Blvd.
Room 4247, MSC 9555
Bethesda, MD 20892
Telephone: (301) 435-1313
FAX: (301) 595-6043
Email: [email protected]

For inquiries related to behavioral and integrated treatment research:

Lisa Onken, Ph.D.
Division of Clinical Neuroscience and Behavioral Research
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Blvd., MSC 9551
Bethesda, Maryland 20892-9551
Telephone: 301-443-2235
Fax: 301-443-8694
E-mail: [email protected]

National Institute of Mental Health:

Mi Hillefors, M.D., Ph.D.
Chief, Psychotic Disorders Treatment Development Program &
Mood and Anxiety Disorders Treatment Development Program
Experimental Therapeutics Branch
Division of Adult Translational Research and Treatment Development
National Institute of Mental Health
National Institutes of Health
6001 Executive Blvd., Room7125 MSC 9632
Bethesda, MD 20892-9632
Rockville, MD 20852 (Visitors, FedEx, UPS, etc.)
Telephone: 301-443-1692
Fax: 301-443-1425
E-mail: [email protected]

2. Peer Review Contacts:

Not applicable.

3. Financial or Grants Management Contacts:

Edith Davis
Grants Management Branch
National Institute on Drug Abuse
6101 Executive Boulevard, Room 260
Bethesda, MD 20892-8403
Telephone: 301-443-6710
Fax: 301-594-6849
Email: [email protected]

Section VIII. Other Information

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Required Federal Citations

Vertebrate Animals:
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 (45 CFR 46) 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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 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 funding opportunity 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.

Inclusion of Women, Minorities, and Children:
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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is 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 SF424 (R&R) application; 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 Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical 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 (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 applications for research involving human subjects and individuals designated as key personnel. The policy is available 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-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicines PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) 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 HHS 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. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles.Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance 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 Part 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 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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.