PRESCRIPTION DRUG ABUSE RELEASE DATE: June 16, 2004 PA NUMBER: PA-04-110 December 8, 2006 - The R01 portion of this funding opportunity has been replaced by PA-07-123, which now uses the electronic SF424 (R&R) application for February 5, 2007 submission dates and beyond. March 2, 2006 (NOT-OD-06-046) Effective with the June 1, 2006 submission date, all R03, R21, R33 and R34 applications must be submitted through using the electronic SF424 (R&R) application. This announcement will stay active for only the May 1, 2006 AIDS and AIDS-related application submission date for these mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms expires on the date indicated below. Other mechanisms relating to this announcement will continue to be accepted using paper PHS 398 applications until the stated expiration date below, or transition to electronic application submission. Replacement R03 (PA-06-340) and R21 (PA-06-339) funding opportunity announcements have been issued for the submission date of June 1, 2006 and submission dates for AIDS and non-AIDS applications thereafter. EXPIRATION DATE for R03 and R21 Non-AIDS Applications: March 2, 2006 EXPIRATION DATE for R03 and R21 AIDS and AIDS-Related Applications: May 2, 2006 Expiration Date for R01 Non-AIDS Applications: November 2, 2006 Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) ( COMPONENT OF PARTICIPATING ORGANIZATION: National Institute on Drug Abuse (NIDA) ( CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.279 THIS PROGRAM ANNOUNCEMNT (PA) CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanisms of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE OF PA This PA supersedes PA-01-048, "Prescription Drug Abuse," issued on February 12, 2001 in the NIH Guide for Grants and Contracts at In revising and reissuing this PA, NIDA continues to encourage research aimed at understanding and reducing prescription drug abuse while supporting appropriate medical use of therapeutic agents with abuse liability. To promote the Nation’s health, research is needed to understand the factors contributing to prescription drug abuse, to characterize the adverse medical, behavioral, and social consequences associated with this abuse, and to develop effective prevention and service delivery approaches and behavioral and pharmacological treatments. Applications to address this issue are encouraged across a broad range of experimental approaches including basic, clinical, epidemiological, prevention, and treatment studies. RESEARCH OBJECTIVES Background Prescription drug abuse is a major public health concern. The 2002 National Survey on Drug Use and Health (formerly known as the National Household Survey on Drug Abuse) reports that 6.2 million Americans age 12 and older are current users of prescription drugs for nonmedical purposes. An estimated 4.4 million used pain relievers, 1.8 million used tranquilizers, 1.2 million used stimulants, and 0.4 million used sedatives. Lifetime nonmedical pain reliever prevalence among youths aged 12 to 17 increased from 2001 (9.6%) to 2002 (11.2%), continuing an increasing trend from 1989 (1.2%). Among young adults aged 18 to 25, the rate increased from 19.4% in 2001 to 22.1% in 2002. The young adult rate had been 6.8% in 1992. Lifetime nonmedical use of stimulants increased steadily from 1990 to 2002 for youths aged 12 to 17 (0.7 to 4.3%). For young adults aged 18 to 25, rates declined from 1981 to 1994 (from 10.9 to 5.9%), then increased to 10.8% in 2002. Rates increased between 2001 and 2002 for both youths (3.8 to 4.3%) and young adults (10.2 to 10.8%). The number of new initiates to nonmedical pain reliever use increased from 628,000 in 1990 to 2.7 million in 2000. About half (52%) of the new users in 2001 were females. In 2001, the number was 2.4 million, not significantly different from 2000. First use of stimulants increased during the 1990s from 270,000 in 1991 to 983,000 in 2000 and 808,000 in 2001. Initiation of tranquilizer use increased steadily during the 1990s, from 373,000 initiates in 1990 to 1.3 million in 2000 and 1.1 million in 2001. The number of sedative initiates has remained below 300,000 per year since 1981. Drug Abuse Warning Network (DAWN) data show that rates per 100,000 of emergency room mentions of narcotic analgesics/combinations (category consists of drugs containing narcotic analgesics alone as well as narcotics in combination with other drugs) have increased 138.7% from 1995 to 2002 and 18.5% from 2001 to 2002. In 2002, the Monitoring the Future study added new questions on the nonmedical use of Vicodin and OxyContin. In both 2002 and 2003, past year use of Vicodin (hydrocodone) and OxyContin (oxycodone hydrochloride) by 12th graders has been about 4% while past year use of Vicodin has been about 10%, raising serious concern about prescription opioid abuse among youth. In addition, concerns have been raised about increasing substance abuse among older adults (age 60 and older) and the potential impact of the aging of the baby boom generation on the need for substance abuse treatment (Gfroerer et al., Drug Alcohol Depend. 69, 127-135, 2003). Alcohol and prescription drug misuse may affect as many as 17% of older adults [Substance Abuse Among Older Adults, SAMHSA/CSAT Treatment Improvement Protocol (TIP) Series 26]. Yet, proper treatment of many medical conditions requires the use of medications that can be misused, abused, and/or lead to dependency. Applications are sought to define the extent of the problem of prescription drug abuse, to characterize this problem in terms of class of drug abused, etiology of abuse, and populations most affected (including racial/ethnic minority and gender analyses). Studies are needed on all classes of prescription drugs with abuse liability, including analgesics, stimulants, sedative/hypnotics, anxiolytics, and muscle building/performance enhancing drugs such as anabolic steroids. Researchers are encouraged to study the relationship between the prescription medication, the indication for which the medication was prescribed (e.g., pain, sleep disorder, anxiety disorder, obesity), and the environmental and individual factors contributing to abuse. Studies are also needed on the factors leading to diversion of prescription drugs into channels of illicit drug distribution and on measures to lessen this diversion, such as science-based education of health professionals. The recent proliferation of internet sites offering controlled substances for sale without a prescription (Forman, JAMA, 290, 889, 2003) requires further investigation. Research is needed to describe the populations most at risk for abuse of particular classes of drugs (including demographic factors and reasons for use), the social norms and social contexts associated with use, the source(s) of these drugs, and the consequences of drug use (e.g., adverse health outcomes such as drug overdose and drug interactions and behavioral and social consequences such as cognitive impairment, absenteeism, and accidents). To reduce prescription drug abuse, research is needed on prevention approaches, service delivery, and behavioral and pharmaco- therapies targeted to particular populations (e.g., the elderly, women, adolescents, health professionals, and those with comorbid substance abuse and mental health disorders and/or medical disorders). Clinical studies are needed that take into account the patient’s age, gender, race/ethnicity, medical and psychiatric diagnoses, and current symptomatology and past and present treatments, as well as the clinical appropriateness or inappropriateness of prescribing practices. Clinical neurobiological investigations using a variety of brain imaging methods also can allow for a better understanding of how these prescription drugs affect brain processes and systems over the life span. Studies are also necessary to determine how attitudes, knowledge, and patterns of prescribing vary across categories of patients and health care providers and how these contribute to inappropriate prescribing practices and disparities in health care. For example, pharmacies may not stock opioid pain medications in racial and ethnic minority communities or low-income communities, and there may be disparities in physicians prescribing practices to minority and low socioeconomic status (SES) patients. Conversely, women are much more likely than men to be prescribed abusable prescription drugs, and prescription drug misuse/abuse among older women is a serious problem that has received little attention and often goes unrecognized by health professionals (CASA Report, June 1998). In general, prescription drug abuse in older adults begins with misuse due to inappropriate prescribing or lack of patient compliance with medication regimens. Continued misuse may progress to abuse and dependence. Older adults may be more vulnerable to prescription drug abuse because of age- related physiological changes that may influence the metabolism and response to prescription drugs, greater likelihood of having undiagnosed psychiatric and medical comorbidities, and difficulties in compliance with complex multiple drug regimens that may increase the likelihood of drug interactions. For example, benzodiazepines are frequently prescribed to older adults, but age-related changes in drug metabolism, interactions with other prescription and over-the-counter medications, and use of alcohol may lead to increased use/misuse/abuse and adverse consequences such as impaired functional capacity and cognition. Yet, older Americans, their families, and their health care and service providers are frequently uninformed about the potential problems with psychoactive prescription drugs and, therefore, do not recognize these problems when they occur. The aging of the baby boom cohort may enhance the occurrence of substance abuse, including prescription drug abuse among older Americans because of this cohort’s prior use and abuse of psychoactive compounds. There is a need for research to develop screening, assessment, and diagnostic instruments (especially for use by health professionals in primary care settings) and prevention and treatment approaches targeted to prescription drug misuse and abuse in older adults. The increased use of prescription drugs among high school and college age youth is also of great concern. In the 2003 Monitoring the Future study, among twelfth graders, annual prevalence of Vicodin use was second only to marijuana use. Young people frequently mix prescription drugs with other drugs of abuse, such as marijuana and alcohol, putting them at risk for drug interactions and overdose. Prescription of methylphenidate and other stimulants to treat attention-deficit hyperactivity disorder (ADHD) has increased in recent years. A new, stand-alone question on nonmedical Ritalin (methylphenidate) use was added to the Monitoring the Future survey in 2001, (Secondary School Students, 2002). Using this new question, annual prevalence rates among twelfth graders was 4.0%; about half (1.9%) reported using only once or twice in the past year, but 0.9% reported using 10 or more times during the year. Studies are needed on the extent of misuse and abuse of prescribed stimulant medications and on the extent to which youth share prescribed stimulants with their peers. There is also a need for developmentally appropriate therapies that can engage and retain adolescents in treatment for prescription drug abuse. In addition, doctors, nurses, dentists, pharmacists, veterinarians, and other health professionals are at risk because of their ready access to prescription drugs with abuse liability. Research is needed to identify the components of effective prevention and treatment approaches targeted toward health professionals. Furthermore, while some health professionals may contribute to the misuse and abuse of prescription drugs because of inappropriate prescribing behaviors, others may provide inadequate pharmacotherapy for pain and other conditions because of fear that their patients will become addicted or that they will incur regulatory scrutiny. There is a need to develop and evaluate innovative science based education approaches for health professionals. Best practices and training protocols for health care workers require research not only on approaches, but also on methods to transfer science into the field. Program Description A range of research is needed to combat prescription drug abuse--from specifying the extent and nature of the problem (including health, behavioral, and social consequences) to developing, evaluating, and disseminating effective prevention and treatment approaches. Research is needed to identify addiction risk factors, including those associated with the chronic therapeutic use of analgesics, stimulants, and sedative-hypnotics for psychiatric and other medical illnesses. Improved means of screening, assessing, and diagnosing those at high risk of abusing or becoming addicted to prescribed psychoactive medications are needed. Research is needed to examine the interaction of patient behavior, social and physical environment, and medical and drug abuse treatment practice to improve prescribing, screening, referral, and treatment processes in the health care system. Treatment studies are needed to develop and evaluate behavioral therapies and combined behavioral and pharmaco-therapies for prescription drug abuse, with particular attention to populations at highest risk (adolescents, women, patients with comorbid psychiatric and/or physical illness, the elderly, and those with a history of polydrug abuse). Basic preclinical and clinical research is needed to understand the neurobiological, behavioral, pharmacological, and genetic basis of prescription drug abuse. Research is needed to identify interactions between abused prescription drugs and other abused drugs and alcohol. Across levels of analysis and research domains, there is also an interest in stimulating development and integration of technologies (for example, from genetic, imaging, proteomic, metabolomic information and approaches) to observe and understand the etiology and biological and behavioral mechanisms associated with prescription drug abuse. Areas of research interest include, but are not limited to, the following: Epidemiology and Prevention Research o Studies, by class of drug, on the nature and magnitude of prescription drug diversion from both licit and illicit sources. Research to identify sources of illicit prescription drugs in different population subgroups. Studies of the demographics of populations abusing each class of prescription drugs, including regional variations and rural-urban gradients. Studies should consider the methodological aspects of measuring prescription drug abuse such as the nomenclature for prescription drugs used in various population groups and the accuracy of recall and reporting of medication names and dosing regimens. o Research on the factors that influence temporal trends in abuse of prescription drugs such as changes in the health care system, prescriptive practices, and sources of prescription medications (local pharmacy, mail order, internet, other) and in the training of health care providers regarding prescribing medications with abuse liability. o Studies on the role of the internet as both a source of prescription drugs and a source of information about these drugs. Studies on the role of the internet and direct-to-consumer advertising in shaping attitudes and in influencing beliefs about the risks associated with prescription drugs. o Studies to identify patient populations who are under- or over-medicated or have difficulty obtaining adequate treatment with controlled substances. Studies on prescribing practices and attitudes of physicians (by specialty area, including primary care physicians) toward prescribing medications with abuse liability to different patient populations (such as children and adolescents, women, the elderly, racial/ethnic minorities, uninsured) and patients with current or past substance abuse problems. o Studies to evaluate whether prolonged treatment with prescription psychoactive drugs for conditions such as ADD/ADHD, sleep disorders, pain, obesity, anxiety disorders, etc. contributes to drug abuse or relapse to drug abuse in vulnerable individuals. o Studies to evaluate whether noncompliance with prescription drug dosing increases the likelihood of transition from misuse to abuse, possibly by inducing sensitization. o Studies to determine how prescription drug misuse and abuse, particularly by pregnant women, children, and adolescents, might increase the risk of abuse/addiction of illicit drugs over the life span. o Studies of the factors that predispose an individual to over-rely on and to misuse psychoactive prescription and over-the-counter drugs (e.g., health beliefs and practices, health promotion behaviors, reliance on media, family and cultural practices). o Studies of the adverse behavioral and social consequences associated with prescription drug misuse, abuse, and dependence, such as impairment in school performance, driving, parenting, job performance, independent living for the elderly, etc. o Studies to determine incidence and prevalence of medical and health consequences of prescription drug misuse and abuse. Of particular interest are studies in those with HIV/AIDS, hepatitis, and other infectious diseases that are prevalent in drug abusers. o Studies to identify, design, and evaluate prevention interventions for those adolescents and college-age youth at increased risk for prescription drug misuse and abuse. Types of prescription misuse and abuse among youth include: 1) the mixing of prescription drugs with other drugs of abuse (e.g., marijuana, alcohol), which places them at risk for drug interactions and overdose; 2) misuse and abuse of prescribed stimulants and providing these drugs to their peers; 3) abuse of dextromethorphan (DXM), an over-the-counter drug, alone and in combination with other drugs of abuse; 4) use of stimulants on college campuses for appetite suppression, wakefulness, increased attention, and euphoria. o Studies to design and evaluate prevention interventions for individuals who may be at increased risk for prescription misuse and abuse in the following populations: 1) individuals with illnesses, such as arthritis, back pain, insomnia, fatigue, obesity, anxiety, eating disorders, etc., who are prescribed abusable prescription drugs; 2) health care professionals; and 3) the elderly. o Studies that theoretically and empirically explore the impact of existing evidence-based drug abuse prevention approaches, or variants of existing approaches, on prescription drug abuse patterns. Basic Preclinical and Clinical Research o Employ basic studies using animal models to probe the effects of prescription drugs on neurobiological, neurochemical, and neurobehavioral processes. o Study possible associations between physical dependence, produced by either medical or nonmedical prescription drug use, and the development of addiction. o Study the pharmacokinetics, pharmacodynamics, and pharmacogenetics of drug- drug interactions between abused prescription drugs and other illicit drugs, as well as between prescription drugs and dietary supplements and drugs for treatment of infections (e.g., antiretrovirals). o Conduct pharmacogenetic studies examining the genetic variation in physiological homeostasis, neurocognitive processes, biological systems and/or metabolic effects of prescription drugs and vulnerability to addiction. o Conduct studies to determine the health consequences of prescription drug abuse and their underlying pathophysiology in diverse populations, e.g., those with HIV/AIDS and other infectious diseases, adolescents, the elderly, women. Consequences may include developmental, psychiatric, metabolic (including nutritional), endocrine, pharmacokinetic/pharmacodynamic drug-drug interactions, or other physiological system effects caused by, or associated with the abuse of prescription drugs. o Research is needed to determine the extent and mechanisms by which abused prescription drugs affect neurobiological mechanism and behavioral processes during development (including prenatal exposure), adolescence and adulthood, including older adulthood. o Determine how prescription drug abuse has a differential effect on brain processes across adulthood, particularly in elderly populations. For example, what are the effects of prescription drugs on normal aging processes in the brain, and do they place individuals at increased risk (or earlier expression) of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and other neurocognitive disorders? o Assess the risk of addiction to prescribed medications as a function of the medical condition for which the drug is prescribed. For example, is the risk of addiction to opioids lessened as a function of the degree of pain present? If so, the mechanism responsible for this variation needs to be examined. o Cross-sensitization and relapse. In animal models determine if exposure to prescription drugs can precipitate relapse or lead to cross-sensitization to other drugs. o Determine the mechanism responsible for feelings of well-being induced by certain steroids (e.g., prednisone). Is the euphoria sufficient to maintain drug-seeking? Do steroids stimulate relapse under, for example, conditions of psychomotor stimulant abstinence? Determine if steroids reduce the aversive effects of drug withdrawal. o Assess whether prescription drugs affect the toxicity of other abused substances. For example, fluoxetine is used in the treatment of depression and obsessive-compulsive disorder (OCD), but it is being misused/abused in an attempt to protect from the neurotoxic action of methamphetamine, ecstasy, and other "club drugs." Studies are needed to determine the consequences of these drug combinations on neural mechanisms and behavioral. o Study the acute and chronic interactions between prescription drugs and illicit substances at the behavioral and cognitive level of analysis. Most notably, what are reinforcing characteristics of drug combinations? o Develop and apply interoperable and scalable analytic, modeling and other computation and information tools (such as those for dynamic semantic profiling, social and other network analysis, and data integration and management) to enable pattern recognition and analysis to facilitate understanding of emerging patterns of use, vulnerabilities, drug use and disease relationships, economic relationships, and other factors related to prescription drug abuse. Treatment and Services Research o Research on the development and testing of effective and comprehensive treatment approaches that may include behavioral, pharmacological, alternative or complementary therapies for individuals who abuse or become dependent on prescription analgesics, stimulants, anxiolytics, or sedative- hypnotics. Behavioral treatment and combined behavioral and pharmacological studies should be informed by the stage model of therapy development, described in detail in the Behavioral Therapies Development Program Announcement ( Treatment studies are encouraged to include tests of the mediators, moderators, key ingredients, and/or mechanisms of action at all stages of therapy development. o Studies to develop and evaluate treatment approaches that maintain abstinence from prescription drug abuse and prevent relapse. o Studies of brief behavioral treatment interventions for prescription drug misuse and abuse in primary care settings. o Studies to develop and test age-appropriate, gender-sensitive, and culturally-relevant treatment approaches for prescription drug abusing individuals. o Studies to adapt existing treatments for other drugs of abuse, or for other conditions, for use with individuals who abuse prescription drugs. o Studies to develop and evaluate new and innovative therapies to treat prescription drug abuse that are based on promising findings from basic behavioral and cognitive research. o Studies to develop and test, or to adapt, developmentally-appropriate behavioral treatments for adolescents who abuse prescription drugs, with particular attention to the types and patterns of drug use among adolescents and the challenges to engaging adolescents in treatment. o Studies to develop and evaluate therapies for individuals who abuse prescription drugs and have comorbid mental disorders, such as depression, anxiety disorders, post-traumatic stress disorder, and eating disorders or comorbid physical disorders such as sickle cell anemia, HIV/AIDS, musculoskeletal disease, etc. associated with chronic pain. o Studies which utilize e-health tools such as computers and portable digital and wireless devices to improve access to treatment for prescription drug abuse and/or augment provision of treatment by health care providers. o Studies to develop and evaluate effective treatment approaches for the management of pain, anxiety, sleep disorders, obesity etc., in substance abusing patients and people with a history of substance abuse. Therapies are needed for patients who are self-medicating in an attempt to manage comorbid medical and/or psychiatric problems. o Studies to develop and evaluate behavioral treatments to improve medication adherence and prevent misuse of prescribed medications among substance abusing patients with comorbid medical illnesses or mental disorders. o Research on effective detoxification strategies for various classes of prescribed drugs with abuse liability. o Pharmacotherapy studies to evaluate the use of medications for new indications in the treatment of prescription drug abuse (e.g., buprenorphine for oxycodone abuse). o Studies to improve the screening, assessment, and recognition of prescription drug misuse, abuse, and dependence among patients being treated in health care settings for medical and/or psychiatric illnesses, especially those which are chronic in nature. o Studies to improve the recognition and referral for intervention of employee prescription drug misuse and abuse in the workplace to ensure timely and appropriate referral for treatment. Research is needed on educational approaches to increase workforce awareness of prescription drug misuse and abuse. o Studies to determine the factors that may affect access to treatment for prescription drug abuse and addiction, including treatment entry, readiness for treatment, retention in treatment, compliance with treatment, and treatment outcomes among prescription drug abusing women, adolescents, older adults, and racial/ethnic minorities. o Studies to identify organizational characteristics (e.g., climate, culture, age, and size), financing, and managerial approaches to providing the most accessible and effective treatment for prescription drug abuse and addiction, including factors that enhance motivation to participate and remain in treatment, compliance with treatment, and relapse avoidance. Research to identify the value added by linkages to relevant treatment services such as psychiatric, wellness, and social services is also welcome. o Research to develop and evaluate effective strategies/approaches for disseminating science-based information on the recognition, prevention, and treatment of prescription drug abuse to health professionals and community- based health care providers. Research to determine the most effective approaches for enhancing utilization of science-based information and whether these approaches actually change practice behaviors. o Research to develop and evaluate innovative health professional prescription drug education programs using new technologies, e.g. palm pilot, interactive computer based programs, virtual reality, etc. o Research in pharmacoeconomics to study optimum drug therapy and health outcomes utilizing quality-of-life assessment and outcomes research. Such studies would provide economic information to inform clinical prescribing decisions and allocation of healthcare resources. MECHANISMS OF SUPPORT This PA will use the NIH research project (R01), small research grant (R03) (PA-03-108: NIH SMALL RESEARCH GRANT PROGRAM (R03), and exploratory/developmental research grant (R21) PA-03-107: NIH EXPLORATORY/DEVELOPMENTAL RESEARCH GRANT AWARD (R21) award mechanisms. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This PA uses just-in-time concepts. It also uses the modular budgeting as well as the non-modular budgeting formats (see Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format. Otherwise follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign institutions/organizations o Faith-based or community-based organizations INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific/research issues to: Dorynne Czechowicz, M.D. Division of Clinical Neurobiology, Development and Behavioral Treatment National Institute on Drug Abuse, NIH, DHHS 6001 Executive Boulevard, Room 4231, MSC 9551 Bethesda, Maryland 20892-9551 Rockville, Maryland 20852 (for express/courier service) Telephone: (301) 443-2237 Fax: (301) 443-8674 E-mail: Lynda Erinoff, Ph.D. Division of Epidemiology, Services and Prevention Research National Institute on Drug Abuse, NIH, DHHS 6001 Executive Blvd., Room 5153 MSC 9589 Bethesda, MD 20892-9589 Rockville, Maryland 20852 (for express/courier service) Telephone: 301-402-1972 Fax: 301-480-2543 E-mail: o Direct your questions about financial or grants management matters to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse, NIH, DHHS 6101 Executive Boulevard, Suite 270, MSC 8403 Bethesda, MD 20892-8403 Telephone: (301) 443-6710 FAX: (301) 594-6849 E-mail: SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: The title and number of this program announcement must be typed on line 2 of the face page of the application form and the YES box must be checked. APPLICATION RECEIPT DATES: Applications submitted in response to this program announcement will be accepted at the standard application deadlines, which are available at Application deadlines are also indicated in the PHS 398 application kit. SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget grant format. The modular budget grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001) at includes step-by-step guidance for preparing modular grants. Additional information on modular grants is available at SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: Applications requesting $500,000 or more in direct costs for any year must include a cover letter identifying the NIH staff member within one of NIH institutes or centers who has agreed to accept assignment of the application. Applicants requesting more than $500,000 must carry out the following steps: 1) Contact IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study; 2) Obtain agreement from IC staff that the IC will accept your application for consideration for award; and, 3) Identify, in a cover letter sent with the application, the IC staff member who agreed to accept assignment of the application. This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to: Center for Scientific Review National Institutes of Health, NIH, DHHS 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) APPLICATION PROCESSING: Applications must be mailed on or before the receipt dates described at The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an Introduction addressing the previous critique. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. PEER REVIEW PROCESS Applications submitted for this PA will be assigned on the basis of established PHS referral guidelines. Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures ( will evaluate applications for scientific and technical merit. As part of the initial merit review, all applications will: o Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by an appropriate national advisory council or board. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to evaluate application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the application’s overall score, weighting them as appropriate for each application. o Significance o Approach o Innovation o Investigator o Environment The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. SIGNIFICANCE: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? INNOVATION: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? ENVIRONMENT: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score: PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below) INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed. ADDITIONAL REVIEW CONSIDERATIONS Sharing Research Data Applicants requesting more than $500,000 in direct costs in any year of the proposed research are expected to include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score. BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Relevance to program priorities REQUIRED FEDERAL CITATIONS ANIMAL WELFARE PROTECTION: Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (, as mandated by the Health Research Extension Act of 1985 (, and the USDA Animal Welfare Regulations (, as applicable. HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II), efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: SHARING RESEARCH DATA: Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (; a complete copy of the updated Guidelines are available at The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at and at Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s)for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG ABUSE: Researchers funded by NIDA who are conducting research in community outreach settings, clinical, hospital settings, or clinical laboratories and have ongoing contact with clients at risk for HIV infection, are strongly encouraged to provide HIV risk reduction education and counseling. HIV counseling should include offering HIV testing available on-site or by referral to other HIV testing service for persons at risk for HIV infection including injecting drug users, crack cocaine users, and sexually active drug users and their sexual partners. For more information see NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS: The National Advisory Council on Drug Abuse recognizes the importance of research involving the administration of drugs to human subjects and has developed guidelines relevant to such research. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Home Page at under the Funding, or may be obtained by calling (301) 443-2755. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the Standards for Privacy of Individually Identifiable Health Information , the Privacy Rule, on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website ( provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on Am I a covered entity? Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284 and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at 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.

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