The purpose of the National Institute on Drug Abuse's (NIDA) Prevention Research Branch (PRB) is to support a developmentally grounded program of research on the prevention of the initiation of drug use, progression to abuse and dependence, and transmission of drug-related HIV infection. This research involves the use of rigorous scientific methods to test theoretically derived hypotheses to advance our understanding of the science of prevention within diverse populations and settings. The program’s focus involves studies targeting the prevention of many substances (often collectively) including but not limited to nicotine, inhalants, marijuana, cocaine/crack, methamphetamine, club drugs, non-medical use of prescription and over the counter drugs, or any of these drugs in combination with alcohol. Studies that support this purpose include investigations of cognitive, behavioral, and social processes as they relate to 1) the development of novel prevention approaches, 2) the efficacy and effectiveness of newly developed and/or modified (or adapted) prevention programs, 3) the processes associated with the selection, adoption, adaptation, implementation, sustainability, and cost effectiveness of science-based interventions, and 4) methodologies appropriate for studying complex aspects of prevention science. Programs of research are intended to provide pathways toward the discovery of population-level approaches for the prevention of drug abuse and dependence, drug-related problems (e.g., mental health, interpersonal violence, criminal involvement, and productivity loss), and drug-related disorders (i.e., comorbid drug and psychiatric disorders, or infections including HIV, hepatitis B (HBV), and hepatitis C (HCV)), and co-occurring, disorders and illnesses.


Significant progress has been made in understanding effective approaches to prevention of drug abuse over the past few decades, in part because of careful attention given to understanding basic, developmental processes involved in the transition to drug use, abuse and dependence. Drug abuse and dependence are disorders that interfere with the normal, healthy functioning of persons across the lifespan, and are preventable causes of medical and psychiatric problems and disorders, injuries, lost income and productivity, and family dysfunction. While the initiation of licit and illicit drug use, a necessary precursor to abuse and dependence, grows dramatically during the adolescent years, this behavior is preceded by proximal and distal biological, psychological, social, and environmental precursors originating as early as the prenatal period. Furthermore, the misuse and illicit use of drugs extends well beyond adolescence and, for some, begins in adulthood, even in late adulthood.

The life course developmental perspective suggests that individual and environmental factors interact to increase or reduce vulnerability to drug use, abuse and dependence. Vulnerability can occur at many points along the life course but peaks at critical life transitions. Thus, prevention researchers should recognize the significance of timing interventions to coincide with important biological transitions, such as puberty; normative transitions, such as moving from elementary to middle school; social transitions, such as dating; and traumatic transitions, such as the death of a parent. In addition, because vulnerability to drug abuse involves dynamic intrapersonal (e.g., temperament), interpersonal (e.g., family and peer interactions) and environmental (e.g., school environment and neighborhood) influences, prevention intervention research must target interactions between individuals and social systems across the life span. To address this complexity, intervention research needs to test strategies designed to alter specified modifiable mediators to determine which are most related to and effective in reducing drug use initiation and escalation, with what audiences, and under what conditions. There is recognition that developmental patterns may vary by gender, gender identity, race/ethnicity, sexual orientation, and other population-based or cultural factors, and that these need to be better understood so that they can be addressed in interventions as appropriate.  Drug use, abuse, and dependence often co-occur with delinquency and criminal behavior, interpersonal violence, mental health problems, HIV, other sexually transmitted infections, and reproductive health problems. Therefore, understanding the prevention of co-occurring problems and their contribution to elevated levels of risk is important to NIDA's mission.

Successful drug abuse and drug-related HIV prevention programs have utilized a number of theoretical perspectives for predicting differential drug use trajectories and elucidating developmentally grounded mediators, or risk and protective factors, amenable to change. Notable among these theories are Problem Behavior Theory, Social Cognitive Theory, and the Social Development Model. Resulting research has focused on prevention approaches involving positive modification of various precursors of substance use, such as sensation-seeking, emotion regulation, aggressive behavior, academic problems and failure, poor social skills, misperceptions of social norms, poor parent-child attachment, and inappropriate parental expectations and responses. Because theoretical grounding of prevention programs is an essential feature for their success, further progress in prevention research relies on a stronger understanding of successful theories and their application and potentially the development of new theoretical approaches or meta-theories.

Prevention context impacts upon the feasibility, acceptability, and effectiveness of prevention approaches. Successful programs have intervened in multiple contexts, such as schools, health care settings, community service organizations, workplaces, and within the family context. Drug abuse and related HIV prevention research is most successful when there is an existing or created delivery system for prevention interventions to be delivered (e.g., the intervention delivery contexts provide ready access to the target population). That is, the more central the delivery context is to the target audience's existing life routines, the more likely the intervention and associated research will be able to recruit and retain members of the target population and have sustainability of the intervention over time.

Audiences or targets for prevention interventions are generally classified into one of three categories depending on level of risk: universal, selective, or indicated. Universal prevention interventions are targeted to the general public or to a whole population group, such as all children in a school. Selective prevention interventions are targeted to individuals or subgroups of the population with defined risk factors for the development of substance abuse, such as children of drug abusers, children of parents in the criminal justice system, sexual minority youth, and youth in the child welfare system. Indicated prevention interventions are targeted to individuals or subgroups that are identified as having non-clinical but detectable signs or symptoms foreshadowing drug abuse, dependence, and addiction. A tiered approach to prevention interventions incorporates two or more of these levels of intervention with increasing intervention intensity for individuals at greater risk or with greater problem severity.

To advance the field, novel interventions must build on basic science findings from diverse fields. Opportunities exist to expand upon our growing knowledge by incorporating neuroscience, genetics, and physiology to better understand prevention pathways in order to improve effect sizes for successful approaches, increase the breadth of impact, develop personalized prevention approaches, and build efficiency or optimization into the processes of increasing protection or decreasing risk.  Furthermore, because of recent advances in a number of disciplines, important opportunities exist to build upon findings from drug abuse etiology and epidemiology research and the fields of human development, neuroscience, criminology, psychology, sociology, anthropology, and communications. An interdisciplinary approach to prevention, with research teams comprised of scientists bringing complementary expertise and critical and innovative research paradigms, will strengthen prevention efforts. In addition, studies addressing the unique opportunities to examine the interaction between biological, interpersonal, intrapersonal, and environmental variables in the context of the design and implementation of prevention research, need to be developed and tested.

Three underdeveloped areas of drug abuse/drug-related HIV prevention research are discussed briefly here: developmental transitions, differential effectiveness and fidelity of implementation, and emerging technologies. Characteristics and differences that contribute to drug abuse risk during late adolescence and emerging adulthood have not been well studied. This is a particularly important area of research because late adolescence is a significant transition point in human development, and the initiation of use of so-called hard drugs often takes place during this period. Other normative transitions during this life course stage, such as learning to drive, entering college, the military, or the first job; and courtship, marriage and the transition to parenthood as well as non-normative life events such as victimization have not been seriously considered as targets for drug abuse prevention interventions. Moreover, very few prevention interventions for later stages of adulthood have been developed despite the fact that individuals who have used licit and illicit drugs, and prescription drugs for non-medical use, for long periods of time without developing dependency can move toward abuse and dependence as the result of biological (e.g., lower tolerance with aging), medical (e.g., onset or ongoing chronic diseases, endocrine system changes, chronic pain; treatment of major medical conditions), normative (e.g., retirement), social (e.g., making new friends in retirement) or traumatic (e.g., loss of a spouse) transitions. Thus, greater attention to a wide variety of transitions and the risk and protective factors related to them is needed for the development and testing of innovative interventions that target high-risk periods across the life course.

Some effective prevention interventions show differential effectiveness by gender, ethnicity, and other factors. Research is needed to understand underlying biological, psychological and social processes and mechanisms that account for these differences so that interventions can be adapted as needed for specific sub-groups while maintaining the integrity of the intervention core components. Methodologies that help identify core elements, subpopulation effects, and other factors related to effective implementation are in need of further development. The importance of fidelity of implementation is well established, yet there are situations where strict adherence is not possible. Developing a better understanding of what constitutes the core content or effective ingredients of an intervention and how modification can be made while maintaining or boosting effect sizes may be a superior approach to developing a wholly new intervention. Moreover, research to elucidate under what conditions adaptation is indicated would advance our capability to understand how to optimize prevention services.

Emerging technologies, such as, social networking tools, and wireless communication (e.g., texting and cell phone applications), may have application to both intervention design and prevention methodology. While the full impact of such changes on prevention programming and research is unknown, possible improvements to intervention processes and data collection methodology should be explored. Technology-assisted interventions have the potential to be both more personalized, through the use of individualized programs, and more confidential, as they involve less face-to-face contact than more traditional methods. Technologies that are promising for their role in prevention research include hand held devices to collect data and new HIV testing technologies, particularly those that identify early infection.  Less is known about whether the integration of media or other high-tech intervention components into existing interventions boosts intervention effectiveness.  Emerging biological modalities for HIV prevention (e.g., pre-exposure prophylaxis) may have differential utilization and adherence where significant substance use is present and integrated biobehavioral interventions are needed to optimally implement these approaches.

Specific Areas of Research Interest

This FOA for R03 applications seeks to support small-scale research efforts across the spectrum of drug abuse and drug-related HIV prevention research. NIDA's drug abuse prevention research program is comprehensive in nature and fully reflects the prevention research mission, objectives, and study areas advanced by the Department of Health and Human Services and the National Institutes of Health. The following sections address drug abuse prevention research areas of specific interest to NIDA. Under each research section, examples of topics requiring further study are given. However, many areas for future research are not addressed, and there is an ongoing emergence of new areas.  Thus, investigators should not view the examples provided as limiting the areas of research of interest to NIDA.

1. Basic Prevention Research

NIDA recognizes the need to maximize the use of existing underutilized approaches and basic science findings for the development of innovative preventive interventions targeting the initiation and escalation of drug abuse and the prevention of drug-related HIV infection. The goal of basic prevention research is to identify and test new prevention paradigms informed by basic science. Basic science discoveries utilized in basic prevention research include findings from biological (e.g. neurobiology, stress reactivity, pubertal maturation, or physical development), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g., social work, criminology, sociology, urban planning, and communications) sciences that address individual and group vulnerabilities to drug use initiation and escalation from experimentation, to occasional use, to abuse. Investigators’ efforts over the past two decades have focused on the translation of basic research to produce prevention programs with proven efficacy and effectiveness in addition to science-based prevention principles. However, much existing basic science on biological, neurobiological, psychological, and social processes and mechanisms has not been fully utilized for purposes of developing and testing innovative, potentially efficacious, drug abuse prevention interventions. Moreover, recent scientific advances have provided opportunities to integrate knowledge from diverse fields such as biochemistry, biology, biomedicine, health care policy, computational science, computer science, education, economics, engineering, geography, genetics, sociology, urban planning, informatics/information science, mathematics, neurobiology, neuroscience, and physiology.

One opportunity for basic prevention research is the translation of intervention findings into further basic science study. Because preventive intervention trials include at least one non-intervention control group, they have unique contributions to make in advancing our understanding of the mechanisms through which risk and protective factors operate, including how biological, psychological, social and environmental factors interact to influence risk or how such mechanisms operate within and across different phases of development or for groups at risk for different reasons (e.g., LGBT), or at different levels of risk (i.e., accumulated risk, chronic vs. acute). Ultimately, this research will have implications for further development of new intervention paradigms or refinement/improvement of existing programs and strategies, as well as for the natural history of problem behaviors and the effect of intervention on those behaviors.

Most basic prevention science investigations are expected to be human laboratory studies or small-scale field randomized controlled trial (RCT) studies of well-defined hypotheses derived from prior research. When appropriate, researchers can propose basic research applications as stand-alone R03 applications associated with a prevention research study in its early stages.

Possible exploratory/developmental research foci include, but are not limited to:

Small-scale studies that use findings on learning styles, cognitive strategies, and neurocognitive functioning to improve or develop targeted prevention strategies.

Small-scale studies examining the interaction between emotional and cognitive responses to prevention messages to construct messages more likely to elicit appropriate responses (e.g., triggering refusal behaviors when confronted with potential drug use situations).

Secondary analyses of prevention trial data to examine understudied mediators and moderators of program effects on hypothesized primary outcome variables and on conceptually related outcomes such as sexual risk taking behaviors.

Research to discern what theoretical approaches have the greatest promise for informing intervention strategies/modalities leading to durable behavior change.

Small-scale studies using basic science research and emerging technologies to explicate under-explored mechanisms of neurobiological risk and to facilitate understanding of the biological and neurobiological effects of social, emotional, and behavioral preventive interventions.

2. Prevention Intervention Research

Research on prevention intervention programs and strategies should focus on the manipulation of presumed causal, malleable factors derived from basic prevention and other studies on the origins, pathways and mechanisms of vulnerability to drug abuse, addiction, and drug-related HIV. Even relatively modest prevention intervention research trials can address complex and varied questions on drug etiology, theory testing, mechanisms of intervention effects, process measures, fidelity measures, and implementation cost in addition to assessing short term and long term trial outcomes.

Three types of prevention intervention research that will be discussed further here include efficacy, effectiveness, and systems research.

Efficacy trials are designed to establish the impact of the intervention approach on targeted outcomes under ideal and well-monitored implementation conditions. In preparation for efficacy research, pilot studies are typically conducted to gather evidence for feasibility and acceptability, and potential efficacy in advance of proposing an efficacy trial. Mechanisms other than the R01 (e.g., R34, R21, and R03) are often more appropriate for pilot studies and other developmental work, such as the testing of methods and materials and manualization of the intervention.  Efficacy trials may be small-scale trials or more moderate in size depending on the level of current evidence for the work and other considerations regarding the design of the trial.

Efficacy trials utilize small randomized controlled trials (RCTs) or, if well justified, other highly rigorous research designs. Quasi-experimental designs are discouraged, except in cases where the research question cannot be tested using a more rigorous approach. It is essential to articulate a theoretical framework or basis for the intervention effects anticipated. The theoretical or empirical basis of the intervention defines the role of mediating factors, that is, how various programmatic components have been designed to alter these elements in order to impact upon measurable intervention outcomes. An important aspect of efficacy studies is determining the relevance and acceptability of the program for translation to real world settings.

Effectiveness trials replicate efficacious strategies and interventions in less controlled, real-world settings with larger more diverse samples, and generally employ a RCT or equivalent research design (e.g., multiple baseline, cross over, etc.). In addition to determining effectiveness, these studies usually incorporate prevention services research questions related to factors such as participant recruitment and retention, dosage, cost, fidelity of implementation, and implementer training (see below for further discussion). That is, they examine issues that affect the transportability of programs to real world settings, facilitators and barriers to implementation, and generalizability to diverse populations and geographic settings.

Systems research takes prevention programs or strategies with demonstrated efficacy and effectiveness to scale. Systems trials are implemented through existing (e.g., schools, primary care settings, workplaces) or newly created delivery systems with large samples. Random assignment to intervention and control conditions remains the ideal study design. A major emphasis of systems trials is identifying and understanding how factors that affect the sustainability of programming operate. Thus, addressing prevention services research questions is a core goal of this type of study. All three intervention study types, efficacy, effectiveness, and systems, generally incorporate a longitudinal design to allow for the examination of the role of moderators, mediators and a variety of proximal and distal outcomes over time.

An important emphasis of NIDA's prevention research program is on prevention services research questions. Prevention services research involves identifying and determining how features internal and external to interventions contribute to efficacy and effectiveness. Examples of internal features are: content, implementation strategies, fidelity, dosage, delivery setting, and implementer training. Examples of external features are: exposure to other programs, media, enforcement of regulations and laws related to substance use and community norms around substance abuse. One important area of prevention services research is replication of efficacious interventions with other population groups and in alternate contexts in an effort to develop a clear understanding of those features that are essential to program integrity (i.e., core elements) and those that can be adapted to meet the needs of specific groups and settings. Prior research suggests that features such as program duration, reinforcement of prevention messages over time, consistency of messages across settings, use of developmentally appropriate content and materials, use of interactive teaching techniques, use of intermittent reinforcement, client-facilitator fit, grouping of clients, and interactions between these features need further investigation to improve the quality of programming and increase the potential for translation into real-world settings. Questions around these and other features that concentrate on the availability, organization, management, financing and sustainability of prevention interventions fall into the broad category of prevention services research. This also includes understanding community-level decision-making regarding the selection, adoption, adaptation, implementation and sustainability of prevention programs, policies and practices.

Prevention services research is integral to intervention research and forms the link between research and practice. For that reason researchers are encouraged to include services research questions that address or inform real-world implementation issues in efficacy and effectiveness trials as appropriate.  In addition, researchers are encouraged to integrate prevention practitioners into the research process, from inception through to completion to ensure that successful interventions meet identified needs and to foster ownership and sustainability.

Examples of prevention topics appropriate for exploratory/developmental R03 research projects include:


Small-scale studies developing and testing strategies to strengthen existing group and environmental anti-drug norms and characteristics that have been show to be protective against drug abuse and addiction.

Small-scale studies developing and pilot testing preventive interventions designed to strategically target understudied periods in the life course, such as intervening in early childhood to alter precursors, intervening in late adolescence with youth who discontinue their education, or intervening in adulthood with individuals experiencing high stress, such as military personnel, returning veterans and their families, displaced, bereaved, or victimized persons, or sexual minorities.

Small-scale studies on the efficacy of drug abuse prevention programs and strategies that are untested but widely used such as: case management, mentoring, job training, and challenge activities.

Small-scale studies pilot testing the efficacy of drug use and/or HIV/STI screening tests for their potential effects in reducing or preventing drug abuse and dependence and/or HIV/STI infection.

Small-scale studies of the effects of environmental manipulations, such as school policies, state or local laws, and local law enforcement strategies, or the built environment on drug use and drug-related activities such as gang involvement.

Small-scale studies developing and pilot testing the efficacy of brief HIV and drug abuse prevention interventions for specific contexts such as primary care settings, federally qualified community health centers, and college or workplace health programs.

Small-scale studies testing theoretically grounded interventions with demonstrated efficacy for preventing drug use for their effects on sexual risk behaviors.

Small-scale studies for the development and pilot testing of new prevention interventions or adaptation and testing of evidence-based interventions for at-risk groups of children and youth who have been underrepresented in research efforts (e.g., military youth and families, children of parents in the criminal justice system and their families, children in foster care and their foster and biological families, adopted children and their families, lesbian, gay bisexual and transgender (LGBT) youth).

Small-scale studies of structural or environmental interventions designed to prevent drug use and abuse in communities.

Small-scale studies of tiered approaches that include screening and implementation of universal interventions and selective or indicated interventions for those who continue to experience difficulties to increase intervention impact in a setting or with a population.

Small-scale studies to identify core elements of intervention models (e.g., features/elements that need to be retained, or those that can be adapted or eliminated to streamline programming) while maintaining or boosting efficacy.

Small-scale studies of culturally congruent intervention approaches to reduce drug abuse and drug-related HIV among Native Americans, Pacific Islanders, and other understudied minority populations that are adversely affected by the consequences of drug use.

Small-scale studies that examine the efficacy of novel strategies for addressing the rise in prescription drug misuse and abuse that reflect the unique roles of medical and dental providers, social networks, and policy makers in prevention.


Secondary analysis of prevention intervention data to better understand the impact of drug abuse prevention intervention on drug use, drug disorders, and sexual risk taking behaviors among specific subgroups of individuals such as high risk youth, females, ethnic minorities, and LGBT youth in order to elucidate the need for intervention modifications and specialized intervention approaches.

Secondary analysis of prevention intervention trial data to assess factors accounting for variation in response to drug and HIV prevention interventions such as psychiatric disorders, family function, environmental exposures, stress responsivity, and cognitive or neurocognitive functioning.

Small-scale studies on adaptation of effective drug abuse and HIV prevention approaches to understand the added value of efforts to customize prevention for specific populations such as underserved racial and ethnic minority populations.

Small-scale studies examining program effectiveness in reducing HIV sexual and drug use risks as well as risks for acquiring related infections (i.e., other sexually transmitted infections, viral hepatitis), where research takes into account emerging knowledge about HIV risks such as population-based biological vulnerability, and network patterns.


Small-scale studies examining how differences in school environments, including drug abuse rules, and their enforcement, and policies, influence mediators of drug abuse (e.g., attitudes, norms and intentions) and eventually substance abuse behaviors with particular attention to the pattern and duration of the environmental change processes.

Small-scale studies of the initiation, development, and continuity of community coalitions to prevent drug abuse, and impact on selection and implementation of effective drug abuse prevention strategies.

Small-scale studies examining access and adaptability of research-based strategies for training high-risk parents (e.g., those who abuse drugs, or in situations where abusive child-rearing practices have been documented) through existing service delivery systems.

Determination of the cost and cost-effectiveness of brief drug abuse and HIV prevention programs that have been integrated into primary care, mental health and community settings, including federally qualified community health centers.

Small-scale studies that examine community-level decision-making regarding the selection, adoption, adaptation, implementation and sustainability of prevention programs, policies and practices.

Small-scale studies of the impact of prevention policies on the prevention of drug use and abuse in communities.

Small-scale studies that examine dissemination of evidence-based prevention interventions in communities.

3. Methodological Research

Methodological research is needed in the field of drug abuse prevention on promising data collection, data management, analysis, and reporting techniques. Special attention should be given to the hierarchical and longitudinal nature of most prevention trial data, the adaptation of measures for intervention cohorts over the course of time and development, the measurement and analysis of complex theoretical process models including moderating and mediating variables, the development of adaptive designs, the problems of missing data and attrition when following intervention and control subjects over time, and the development of analytic strategies to determine important features of prevention interventions (i.e., core components). NIDA supports the adaptation and assessment of proven scientific procedures from other disciplines to determine their applicability to drug abuse prevention research such as those from systems science. Specific areas of research include:

Development, testing, and application of complex statistical models to examine differential impacts of preventive interventions across individuals, across time, and across contexts.

Designs to improve causal inference from non-experimental and quasi-experimental research and natural prevention experiments.

Research to improve the analysis of longitudinal data—in particular, the analysis of correlated data, the modeling of different sources of error, and techniques for dealing with missing data at various levels of aggregation that may occur in prevention trials, as well as refining methods for evaluating effects in small, high risk subpopulations.

Methodological research to improve the analysis of complex prevention trial data, including the statistical modeling of non-response and other survey errors.

Analytic methods that appropriately model social structures, social processes, and spatial relationships such as social networks, social influence, diffusion, and contextual effects within randomized prevention trial datasets.

Methods for the detection and analysis of non-linear or discontinuous changes in response to preventive interventions.

Methodological research examining complex interactions between qualitative (e.g., process data) and quantitative outcome data.

Applications of systems science to improve the ability of complex trials to model real world clinical operations and decision making.

Research that evaluates ethical issues in the implementation of prevention interventions in particular populations, settings, or policy contexts, including evaluation of specific intervention modalities, study designs, and data collection methods.

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