NIH – Behavioral & Integrative Treatment Development Program (R01, R34 Clinical Trial Optional)

March 12, 2019 by ssw3an@virginia.edu

The following description was taken from the R01 version of this FOA.

The goal of this Funding Opportunity Announcement (FOA) is to encourage research grant applications on the development and testing of behavioral and integrative treatments for drug and alcohol use, abuse and dependence. This FOA reaffirms the continued commitment of NIDA, NIAAA and OBSSR to major programs of research on behavioral and integrative treatments. The term “behavioral treatments” is used here in a broad sense and includes but is not limited to: psychotherapies, cognitive, relapse prevention, remediative, rehabilitative, skills training, counseling, family, and exercise therapies. Screening, brief, computerized, adherence, prevention interventions for HIV risk behaviors, and interventions that target therapist training and fidelity also are included. Integrative refers to combinations with other treatments, including pharmacotherapies or other complementary approaches. The development and testing of putative targets and mechanisms of behavior change, as well as the use and development of valid and reliable assessment tools are crucial to the three stages of treatment research supported under this initiative:

Stage I (treatment generation, refinement) encompasses all activities related to the creation of a new behavioral intervention. This stage also includes the modification, adaptation, or refinement of an existing intervention (Stage IA). Stage I culminates in feasibility and pilot testing (Stage 1B). For example, one can conduct Stage I studies in research settings, with research therapists and research subjects; or in community settings with community providers.

Stage II (“Efficacy”) research consists of experimental testing of promising behavioral interventions in research settings, with research-based therapists/providers.

Stage III (“Efficacy in Real-World”) research consists of experimental testing of promising behavioral interventions in community settings, with community-based therapists/providers and patients, while maintaining a high level of control necessary to establish internal validity.

Stages I, II, and III all include a focus on theory-derived, targets/putative moderators, mediators, and change mechanisms that underlie the treatment, and studies that optimize combined, sequential, or integrated behavioral/pharmacological treatments.

Significance

Behavioral treatments play a critical role in most evidence-based substance abuse interventions, and often constitute the entire treatment. This FOA (in conjunction with the companion FOA, PAR-19-213, using the R34) will support Stages II and III behavioral and integrative intervention research with the goal to advance science, including treatments and interventions that are intended to be more efficient, better tailored to individuals, or more readily transported to the community. Over the past two decades, numerous evidence-based behavioral and integrative treatments for addiction have been created. With advances in neuroscience and pharmacology, it is evident that to improve clinical outcomes, more needs to be done to incorporate new scientific discoveries into behavioral treatment and intervention development. In addition, as more information is elucidated about how treatments work and for whom, and new technologies become available, more can be done to make treatments more easily transportable to community settings. The Behavioral and Integrative Treatment Development Program seeks to achieve these goals.

For alcohol abuse and dependence, most of the treatments available in the U.S. have been behavioral in nature. A large number of clinical trials demonstrated effectiveness for several types of behavioral therapies, including cognitive behavioral therapy, motivational enhancement therapy, marital family therapy, brief interventions, and the community reinforcement approach. Although progress has been made in a broad range of behavioral interventions to treat alcohol abuse and dependence, many alcohol-dependent individuals do not respond adequately to currently available behavioral therapies. For alcohol abuse and dependence, this FOA supports research to develop new innovative behavioral therapies or modify existing treatments to improve their effectiveness and devise ways to improve the engagement, retention, adherence, and outcome of alcoholism treatment across various populations of alcohol dependent and abuse subjects.

The Stage Model describes behavioral intervention development as composed of six stages: basic science (Stage 0), intervention generation, refinement, modification, and adaptation and pilot testing (Stage I); traditional efficacy testing (Stage II); efficacy testing with real-world providers (Stage III); effectiveness research (Stage IV) and; dissemination and implementation research (Stage V). Under this FOA, only stages I, II and III are supported. Intervention development with the stages should be viewed as iterative, recursive, and bidirectional.

Stage I: Stage I encompasses all activities related to the creation of a new behavioral intervention, or the modification, adaptation, or refinement of an existing intervention (Stage IA), as well as feasibility and pilot testing (Stage 1B). Stage I may involve translational basic to applied (sometimes referred to as “T1”) research. Stage I also may involve the modification or adaptation of interventions for ease of implementation in real-world settings. For example, projects can be conducted in: research settings with research therapists/providers, but they also can be conducted in “real world” or community settings with community therapists/providers. One goal of a Stage I project is to provide necessary materials and information to proceed to a later phase Stage I, Stage II or Stage III project. An equally important goal is to obtain scientific knowledge of the processes that lead to behavior change (i.e., behavioral, cognitive, social or biological change mechanism at multiple levels of analysis).

Stage I research is iterative and may involve: 1) identifying promising basic or clinical scientific findings relevant to the development or refinement of an intervention; 2) generating/ formulating theories relevant to intervention development and putative change mechanisms; 3) operationally defining, and standardizing new or modified principle-driven interventions; 4) initial or pilot testing of the intervention; 5) experimentally testing the mechanisms and principles of behavior change of the intervention; and 6) as necessary, further refining the intervention.

This Stage Model presumes that intervention development is incomplete if no materials and methods are available to ensure faithful administration of an intervention. Therefore, therapist/provider training and fidelity assessment and enhancement methods are an integral part of behavioral intervention development.

Stage I research can be conducted to generate, modify, refine, adapt, or pilot-test: 1) behavioral treatment interventions; 2) HIV prevention interventions; 3) medication adherence interventions; 4) components of a behavioral intervention; 5) therapist/provider training and supervision interventions; 6) interventions to ensure maintenance of the fidelity of intervention. The proposed study can be conducted prior to taking the intervention to an efficacy study, or after an intervention has proven efficacious.

Stage II: Stage II research consists of the testing of promising behavioral interventions in research settings, with research therapists/providers while maintaining a high level of control necessary to establish internal validity. This treatment stage also involves examining mechanisms of behavior change. Stage II does not specify a particular research design. Testing of interventions may be done in randomized clinical trials, but may also be conducted using other methodologies as appropriate (e.g., adaptive designs, multiple baseline single-case designs, A-B-A designs, etc.). Stage II studies may include exploration of intervention components, dose-response, and theory-derived moderators.

Proceeding from Stage I to Stage II (or Stage III in the case of an intervention developed in or ready for a community setting) presumes that promising pilot data exist. If sufficiently strong evidence of promise does not exist, but if there is a good rationale for additional modification of the intervention, such modification can be proposed in a subsequent Stage I study.

Information obtained from Stage II studies may be used to inform future Stage I studies. For example, if it is shown that an intervention works for some people, but not for others, especially if such a moderator effect makes conceptual sense, a Stage II study may lay the groundwork for a Stage I application aimed at developing an intervention (or modifying the intervention) for people who were unresponsive to the initial intervention.

Stage III: Stage III research determines efficacy in community settings, with community therapists/providers. Although Stage III occurs in real-world settings, investigators should maintain a high level of control to establish internal validity. Proceeding directly from Stage I to Stage III requires Stage I research to be promising and requires the existence of methods to ensure fidelity of delivery of an intervention, along with therapist training materials (as required by the intervention).

Stage III does not specify a particular research design. Testing of interventions may be done in randomized clinical trials but may also be conducted using other methodologies (e.g., adaptive designs, multiple baseline single-case designs, A-B-A designs, etc.). Stage III studies may include examinations of intervention components, dose-response, and theory-derived moderators.

Information obtained from Stage III – or Stage II – studies may be used to inform future Stage I studies. For example, if it is shown in Stage III that an intervention works for some people, but not for others, a Stage III study may lay the groundwork for a Stage I application aimed at developing an intervention (or modifying the intervention) for people who were unresponsive to the initial intervention.

Examination of the mechanism of action of interventions is considered to be an integral part of all Stages of intervention development research.

The objective of this announcement and its companion funding opportunity is to ensure sufficient emphasis and support for Stages I through III of behavioral and integrative treatment research. The supported studies will support translation of scientific knowledge into more efficient behavioral, combined behavioral and pharmacological, integrative and complementary treatments so that they ultimately can be effectively transported from research to the community.

Specific Areas of Research Interest

The overarching goal of this funding opportunity announcement (FOA) is to produce maximally efficacious behavioral interventions (individual and group) – to treat substance abuse, promote medication/treatment adherence, and prevent HIV – that take advantage of new knowledge in neuroscience, new technologies and pharmacotherapies that may improve tangible outcomes of behavioral interventions (e.g., improving cognitive function). This FOA underscores the importance of fostering research aimed at boosting intervention effects to produce targeted treatments for different types of substance abusing populations (including pregnant women, populations with comorbid psychiatric disorders, and prisoners) or populations with pain. Stages of treatment development will include Stage I, Stage II and Stage III efficacy studies (randomized clinical trials, adaptive designs, SMART designs, experimental therapeutics approach) of behavioral, combined, or integrated treatment interventions, adherence interventions, and prevention interventions for HIV risk behaviors. This includes treatment dose-response studies, and studies of the optimal sequencing of treatment, adherence, and HIV prevention interventions. Research on the treatment of any substance of abuse, including illicit drugs, prescription medications, nicotine (including e-cigarette cessation), alcohol and multiple drugs is encouraged. Of particular interest are studies that seek to determine basic mechanisms of behavior change, within the context of behavioral treatment research. Therefore, applicants are strongly encouraged to include (and if necessary develop) measures of proposed mediators, moderators, and mechanisms of behavior change relevant to their intervention. This may include, for example, behavioral, cognitive, social, affective, and/or neurobiological targets. Grant applications submitted under this PAR should indicate and make explicit the stage of treatment development, as described above (hybrid studies are acceptable).

Specific areas of interest include, but are not limited to:

  • Research to elucidate purported mechanism of action and targets of behavioral interventions at multiple levels of analysis. This includes determination of underlying biological and/or neurobiological mechanisms (e.g., as measured by imaging methodologies, skin conductance, or other biological/physiological indices) of the interventions associated with the behavioral, cognitive, affective, or social mechanisms of interventions.
  • Research that uses innovative technologies (digital therapeutics, including mobile applications and other platforms, virtual reality, wireless monitoring and biofeedback, imaging tools for biofeedback) to develop, improve and systematically measure behavioral interventions including the use of imaging methods to predict outcomes from behavioral interventions. Additionally, neuromodulation devices to augment behavior therapies.
  • Research that incorporates of genetic/epigenetic methodologies to help understand the variability in outcomes as result of therapeutic interventions.
  • Research that evaluates the use of medications to improve the efficacy of behavioral interventions.
  • Research on the essential components of a behavioral treatment, adherence or therapist training intervention
  • Stage II and III treatment development research aimed at facilitating the implementation of an intervention, testing behavioral interventions within primary care settings
  • Research to promote adherence to pharmacotherapies, such as buprenorphine, methadone, depot naltrexone, lofexidine, naloxone, or HAART, in substance abuse treatment populations.
  • Studies that develop safe and effective psychosocial interventions to improve the outcomes of pharmacotherapies for SUDs including OUD and overdose reversal.
  • Research on tobacco harm reduction strategies such as switching from combustibles to e-cigarettes.
  • Research to adapt or modify scientifically supported substance abuse treatments, adherence interventions, or HIV prevention interventions for drug and alcohol users to enhance the application of and boosting treatment potency among health disparities populations.

Special Considerations

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.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Applications under this FOA are encouraged, but not required, to apply approaches and tools developed under the NIH Common Fund’s Science of Behavior Change (SOBC) Program. These include: use-inspired research on mechanisms of change at multiple levels of analysis; assays for self-regulation, interpersonal processes and stress that have evidence as malleable targets for behavior change (see https://osf.io/zp7b4) developed under the SOBC program; and an experimental medicine approach which requires a clear a priori specification of the intended mechanistic target(s) of an intervention, and methods that test the degree to which an experimental manipulation or intervention engages those targets. For more information about the SOBC program, please see: https://commonfund.nih.gov/behaviorchange.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA’s credibility and reputation within the scientific community.  Please see (http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding-) for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit:  NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org).  Please see NOT-DA-12-008 (https://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details

Deadlines:  July 23, 2019; March 23, 2020; July 23, 2020; March 23, 2021, July 23, 2021, March 23, 2022 (for both AIDS and non-AIDS proposals; letters of intent due 30 days prior to the deadline)

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Filed Under: Funding Opportunities