NCCIH Clinical Trial Funding Opportunity Announcements

The National Center for Complementary and Integrative Health (NCCIH) no longer accepts most clinical trial applications through the Parent R01 (See NOT-AT-20-001). NCCIH has published a series of clinical trial-specific Funding Opportunity Announcements (FOAs) for investigators to use instead of the Parent R01. They focus on 1) mind and body intervention studies and 2) natural product studies, targeting support of all phases of clinical intervention development.

Clinical trials are particularly important to NCCIH. We study health interventions widely used by the American public—interventions often used with scarce evidence of efficacy. We see substantial promise in many of these interventions, but we recognize that the evidence supporting their use is often incomplete. Our clinical trial FOAs will help to address gaps in current research and build a strong evidence base.

NCCIH Clinical Trial FOAs Support Continuum of Clinical Research

With the continuum of available NCCIH clinical trial FOAs, we support investigators working on the “building blocks” that bridge the gap from basic research to high-impact clinical trials. We provide pathways via these FOAs to support all developmental steps that may lead to major clinical trials on complementary and integrative health approaches. Applications to nearly all of the NCCIH clinical trial FOAs listed below will be assessed by special emphasis review panels familiar with our research priorities and the goals of each FOA.

The National Institutes of Health (NIH) defines a clinical trial as “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” (NOT-OD-15-015). NIH defines a mechanistic study (which can be a type of clinical trial) as: “A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention.”

NCCIH recognizes a difference between clinical trials that are designed to answer specific questions about the clinical effect of interventions and mechanistic studies that have the primary goal of understanding how an intervention works.

  • A mechanistic study is defined as one designed to understand the mechanism of action of an intervention, a biological process, or the pathophysiology of a disease.
  • A clinical outcome study is defined as one with the objective of determining the clinical safety, tolerability, feasibility, efficacy, and/or effectiveness of pharmacologic, nonpharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions.

NCCIH has developed a range of FOAs to support mechanistic research and research on clinical outcomes that support the full spectrum of human subjects research.

NCCIH Framework for Human Subjects Research

NCCIH clinical trial framework process

How NCCIH Uses the Parent R01 for Human Subjects Research

The NIH now offers three options for the Parent R01 (see comparison of FOA types by clinical trial allowability):

  • Parent R01 Clinical Trial Not Allowed (PA-19-056): NCCIH will continue to accept applications to this FOA for observational studies such as survey studies, cohort studies, or case-control studies, as well as secondary analyses of existing data sets or banked samples.

  • Parent R01 Clinical Trial Required (PA-19-055): NCCIH will only accept applications that propose human mechanistic trials/studies; no applications will be accepted that include any specific aims that propose to assess efficacy or effectiveness of any intervention (see NOT-AT-20-001).

  • Parent R01 Basic Experimental Studies with Humans Required (PA-19-091): NCCIH will accept applications that propose basic science experimental studies involving humans, referred to in NOT-OD-18-212  as “prospective basic science studies involving human participants.” These studies assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind.

NCCIH has developed a suite of clinical trial FOAs to support the full range of clinical trial types for both mind and body and natural product interventions. Investigators are strongly encouraged to apply to one of NCCIH’s clinical trial FOAs (see Tables below) instead of the Parent R01 FOAs. Applicants are encouraged to contact nccihderinquiries@mail.nih.gov for initial advice on choosing an FOA to match their stage of science. Once applicants have chosen a specific FOA and developed a specific aims page, they are encouraged to contact the Scientific Research contact listed in the FOA and in the table below for further feedback prior to applying.

For More Information

Mind and Body Clinical Trial Funding Opportunities


Funding Opportunities for Mechanistic Outcomes (Investigates How the Intervention Works)

Title

NIH Guide #

Released

Expires

Contact

Notice of Special Interest (NOSI): Fundamental Science Research on Complementary and Integrative Health Approaches, Including Natural Products or Mind and Body Interventions (NOT-AT-21-006)

PA-20-185;

PA-20-184;

PA-20-183;

PA-20-195;

PA-20-196;

PA-20-194

03/19/21

09/08/24

Wen Chen;

Inna Belfer;

Craig Hopp;

Erin Quinlan;

Hye-Sook Kim;

Merav Sabri;

This NOSI solicits applications that focus on basic and mechanistic research on complementary and integrative health approaches and investigates the following key aspects:

  • The complementary and integrative health approach/intervention itself
  • Biological, behavioral, psychological, and/or social systems
  • Studies on novel platforms (e.g., cell cultures, animal models, human subjects, or computational models/in silico systems)

In this context, mechanistic research refers to studies examining the interactions between the approach and the systems (e.g., biological, behavioral, psychological, and social). The scientific scope of the work includes (but is not limited) to the following research areas either in animal models or in research participants:

(1) Basic Research: Investigate the connections and interactions of multiple systems (e.g., two or more physiological systems); uncover and evaluate innovative or unique mechanisms or multisystem effects modulated by the complementary and integrative health approach; assess mechanisms or targets of complementary and integrative health approaches in underserved populations.

(2) Research on Mechanisms of Complementary or Integrative Interventions: Investigate the mechanistic effects of complementary and integrative health approaches in a variety of systems, including multiple physiological systems and their interactions or multimodal interventions in one or more physiological systems; investigate novel interoceptive processes; investigate real-time operations in the central nervous system or other physiological systems during meditation and other mind and body approaches; ascertain the interactions of physiological and psychological systems in response to these interventions, and identify and evaluate potential biomarkers that predict the therapeutic response.

(3) Technology or Method Development Research: Develop and evaluate innovative mechanistic studies of complementary and integrative health approaches in a variety of areas, including humanized cellular or organ systems or genetically modified or preclinical animal models; quantitative assessments of interoception processes, myofascial tissues, or lymphatic systems; untargeted bioinformatic approaches to identify active components in a natural product mixture; models capable of illuminating mechanisms of action for natural products and probiotic treatments; and diagnostic procedures.

If this topic aligns with your research interests, please contact us at nccihderinquiries@mail.nih.gov with your specific aims before submitting your application.

Promoting Research on Music and Health: Phased Innovation Award for Music Interventions (R61/R33 Clinical Trial Optional)

PAR-20-266

07/15/20

06/15/23

Wen Chen

The purpose of this Funding Opportunity Announcement (FOA) is to promote innovative research on music and health with an emphasis on developing music interventions aimed at understanding their mechanisms of action and clinical applications for the treatment of many diseases, disorders, and conditions. Given the emphasis on innovation, little or no preliminary data are needed to apply under this FOA. Because of the need for a multidisciplinary approach, collaborations among basic researchers, translational science researchers, music intervention experts, other clinical researchers, music health professionals, and technology development researchers are encouraged. The FOA uses a phased R61/R33 funding mechanism to support mechanistic research and to evaluate the clinical relevance of music interventions. The R61 phase will provide funding to either investigate the biological mechanisms or behavioral processes underlying music interventions in relevant animal models, healthy human subjects, and/or clinical populations, or can be used to develop innovative technology or approaches to enhance music intervention research.” The second (R33) phase” will provide support for further mechanistic investigations in human subjects or animal models, intervention development, or pilot clinical studies. The pilot clinical studies may focus on intervention optimization/refinement, feasibility, adherence, and/or identification of appropriate outcome measures to inform future clinical research. Transition from the R61 to the R33 phase of the award will depend on successful completion of prespecified milestones established in the R61.


Funding Opportunities for Clinical Outcomes (Intervention Development and Testing for Conditions of Interest)

Title

NIH Guide #

Released

Expires

Contact

Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required)

PAR‑21‑240

06/14/21

03/12/24

Peter Murray, Ph.D.

The goal of this funding opportunity is to support early phase clinical trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) for conditions that have been identified by the National Center for Complementary and Integrative Health (NCCIH) as high-priority research topics. This funding opportunity is intended to support feasibility clinical trials, which will provide data that are critical for the planning and design of a subsequent clinical efficacy or effectiveness study or a pragmatic trial. The data collected should be used to fill gaps in scientific knowledge necessary to develop a competitive full-scale clinical trial, including but not limited to the following: examining feasibility and acceptability of interventions lacking published data; adapting an intervention to a specific population; refining the intervention to determine the most appropriate frequency or duration; determining feasibility of recruitment, retention, and data collection procedures; refining and assessing the feasibility of protocolized multimodal interventions; or examining acceptability of and adherence to control conditions. This funding opportunity announcement (FOA) will not support randomized clinical trials that test or determine efficacy or effectiveness, nor will this FOA support repetition of feasibility or acceptability research that has been previously conducted in the same or similar patient populations with the same or a similar intervention (common uses/misuses). Applications that propose solely to write a protocol or manual of operations or to develop infrastructure for a clinical trial are not appropriate for this announcement. Applications must propose to conduct a feasibility clinical trial. The subsequent larger trial should have the potential to make a significant impact on public health.

Prior to submitting to this FOA, applicants are encouraged to contact the appropriate NCCIH scientific/research contact person for the science area of the planned application.

NCCIH Multi-Site Feasibility Clinical Trials of Mind and Body Interventions (R01 Clinical Trial Required)

PAR‑21‑241

06/14/21

03/12/24

Della White, Ph.D.

This Funding Opportunity Announcement (FOA) invites applications for investigator-initiated clinical trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) in National Center for Complementary and Integrative Health (NCCIH)-designated areas of high research priority. Applications submitted under this FOA are expected to propose a multi-site feasibility clinical trial to assess whether the intervention can be delivered with fidelity across sites; demonstrate feasibility of recruitment, accrual, and randomization of participants across sites; demonstrate participant adherence to the intervention, as well as retention of participants throughout the study across sites; and/or demonstrate feasibility of data collection across sites in preparation for a future fully powered, multi-site efficacy/effectiveness trial. The need for multi-site feasibility trials is expected to be justified by sufficient preliminary data from previous single site feasibility or acceptability trial(s) or the published literature. This FOA will not support clinical trials that determine efficacy or effectiveness (common uses/misuses). The data collected should be used to fill gaps in scientific knowledge and be necessary to develop a competitive fully powered multi-site clinical trial that has the potential to make a significant impact on public health.

Prior to submitting to this FOA, applicants are encouraged to contact the appropriate NCCIH scientific/research contact person for the science area of the planned application.

Clinical Coordinating Center for NCCIH Multi-Site Investigator-Initiated Clinical Trials of Mind and Body Interventions (Collaborative UG3/UH3 Clinical Trial Required)*

PAR‑21‑243

06/14/21

03/12/24

Lanay Mudd, Ph.D.

This Funding Opportunity Announcement (FOA) encourages applications for investigator-initiated multi-site clinical trials (e.g., efficacy, effectiveness, or pragmatic trials) to study the effects of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) in National Center for Complementary and Integrative Health (NCCIH)-designated areas of high research priority. Clinical Coordinating Centers should develop and implement the proposed fully powered multi-site clinical trial. The objective of a Clinical Coordinating Center application is to present the scientific rationale and a comprehensive scientific and operational plan for the clinical trial. Clinical Coordinating Center applications are expected to describe plans for project management, participant recruitment and retention strategies, performance milestones, scientific conduct, and dissemination of results. Clinical Coordinating Center applications submitted under this FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) funding mechanism.

In addition, an accompanying Data Coordinating Center application (U24), submitted under PAR-21-242, proposing a data analysis and data management plan for the clinical project is required. Both a Clinical Coordinating Center application and a corresponding Data Coordinating Center application need to be submitted simultaneously for consideration by NCCIH. For additional information about the mission, strategic vision, and research priorities of NCCIH, applicants are encouraged to consult the NCCIH website: (https://nccih.nih.gov/about/plans).

Applicants are encouraged to contact the appropriate scientific/research contact for the area of science for which they are planning to develop an application prior to submitting to this FOA.

Data Coordinating Center for NCCIH Multi-Site Investigator-Initiated Clinical Trials of Mind and Body Interventions (Collaborative U24 Clinical Trial Required)*

PAR‑21‑242

06/14/21

03/12/24

Lanay Mudd, Ph.D.

This Funding Opportunity Announcement (FOA), using the U24 grant funding mechanism, encourages applications for a collaborating Data Coordinating Center (DCC) application that accompanies an investigator-initiated multi-site clinical trial (Phase III and beyond) application submitted under PAR-21-243. The DCC application must be specific to the companion Clinical Coordinating Center (CCC) application. The objective of the DCC application is to propose a comprehensive plan that provides overall project coordination and administrative, data management, and biostatistical support for the proposed clinical trial. Both a DCC application and a corresponding CCC application need to be submitted simultaneously for consideration by the National Center for Complementary and Integrative Health (NCCIH).

Trials for which this FOA applies must be relevant to the research mission of NCCIH and considered a high priority by the Center. For additional information about the mission, strategic vision, and research priorities of NCCIH, applicants are encouraged to consult the NCCIH website: (https://www.nccih.nih.gov/).

Applicants are encouraged to contact the appropriate the scientific/research contact for the area of science for which they are planning to develop an application prior to submitting to this FOA.


*UG3/UH3 and U24 are companion announcements. Investigators must submit applications to both FOAs together. The combined budget of the Clinical Coordinating Center and Data Coordinating Center applications determines whether investigators need to request permission to submit an application with a budget greater than $500,000 direct costs in any year. Investigators can learn more about NCCIH’s policy on applications for large budget clinical trials on the NCCIH website.

Natural Product Clinical Trial Funding Opportunities


Funding Opportunities for Mechanistic Outcomes (Investigates How the Intervention Works)

Title

NIH Guide #

Released

Expires

Contact

NCCIH Natural Product Early Phase Clinical Trial Phased Innovation Award (R61/R33 Clinical Trial Required)

PAR-20-218

05/20/20

05/08/23

Wendy J. Weber, N.D., Ph.D., M.P.H.

This FOA encourages applications for investigator-initiated early phase clinical trials of natural products (i.e., botanicals, dietary supplements, and probiotics), which have a strong scientific premise to justify further clinical testing. Under this FOA, trials must be designed so that results, whether positive or negative, will provide information of high scientific utility and will support decisions about further development or testing of the natural product.

This FOA will provide up to two years (R61 phase) of support for milestone-driven testing of bioavailability, pharmacokinetics, and assessment of the natural products effect (i.e., measure of mechanism of action) when used by humans on a biological signature(s). If milestones in the R61 phase are achieved, up to 3 years of additional support (R33 phase) may be awarded to replicate the impact of the natural product on the biological signature(s) when used by humans and assess whether there is an association between the degree of the impact on the biological signature and functional or clinical outcomes in a patient population. Applications can design R33 studies to determine how to optimize the impact of the natural product on the biological signature by (1) optimizing the delivery of the natural product by dose or formulation; (2) combine the natural product with another treatment approach that is known to impact the same biological signature; or (3) study the impact of the natural product in a target population that is more responsive.  This FOA will not support efficacy or effectiveness trials, nor will it support trials to test natural products for the treatment or prevention of cancer.

NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required)

PAR-20-217

05/20/20

05/08/23

Wendy J. Weber, N.D., Ph.D., M.P.H.

This FOA encourages applications for investigator-initiated early phase clinical trials of natural products (i.e., botanicals, dietary supplements, and probiotics), which have a strong scientific premise to justify further clinical testing. Under this FOA, trials must be designed so that results, whether positive or negative, will provide information of high scientific utility and will support decisions about further development or testing of the natural product.

This FOA will provide up to 3 years support for studies to replicate the impact of the natural product on the biological signature(s) when used by humans and assess whether there is an association between the degree of the impact on the biological signature and functional or clinical outcomes in a patient population. Applications can design studies to determine how to optimize the impact of the natural product on the biological signature by (1) optimizing the delivery of the natural product by dose or formulation; (2) combine the natural product with another treatment approach that is known to impact the same biological signature; or (3) study the impact of the natural product in a target population that is more responsive. This FOA will not support efficacy or effectiveness trials, nor will it support trials to test natural products for the treatment or prevention of cancer.


Funding Opportunities for Clinical Outcomes (Intervention Development and Testing for Conditions of Interest)

Title

NIH Guide #

Released

Expires

Contact

NCCIH Natural Product Mid Phase Clinical Trial Cooperative Agreement (U01 Clinical Trial Required)

PAR-20-216

05/20/20

05/08/23

Wendy J. Weber, N.D., Ph.D., M.P.H.

This Funding Opportunity Announcement (FOA) invites cooperative agreement applications for investigator-initiated clinical trials of natural products to treat clinical symptoms such as those associated with sleep disturbance, pain conditions, or some mental health conditions (e.g., mild to moderate depression, anxiety, and post-traumatic stress), or examine the effects of probiotics and other natural products on gut-microbiome interactions with the brain and/or immune system. All applications submitted under this FOA must be supported by sufficient preliminary data of bioavailability and documentation that the natural product produces a replicable and measurable biological signature (i.e., measure of the mechanism of action), whenever it is possible or practical to measure and used by the patient population of interest.

Clinical Coordinating Center for NCCIH Multi-Site Investigator-Initiated Clinical Trials of Natural Products (Collaborative UG3/UH3 Clinical Trial Required)

PAR-20-215

05/20/20

05/08/23

Wendy J. Weber, N.D., Ph.D., M.P.H.

This FOA encourages cooperative agreement applications for investigator-initiated multi-site clinical trials (Phase III and beyond) to study the effects of natural products in NCCIH designated areas of high research priority. Applicants should describe plans for a Clinical Coordinating Center to develop and implement the proposed multi-site clinical trial. The objective of the Clinical Coordinating Center is to provide the design scientific rationale and a comprehensive scientific and operational plan for the clinical trial. The Clinical Coordinating Center is expected to be responsible for project management, participant recruitment and retention strategies, performance milestones, scientific conduct, and dissemination of results. Clinical Coordinating Center applications submitted under this FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) funding mechanism.

In addition, an accompanying Data Coordinating Center application, submitted under PAR-18-697, proposing a data analysis and data management plan for the clinical project is required.

Both a Clinical Coordinating Center application and a corresponding Data Coordinating Center (DCC) application must be submitted simultaneously for consideration by NCCIH.

Natural Product, Multi-Site, Clinical Trial, Data Coordinating Center (Collaborative U24 - Clinical Trial Required)

PAR-20-219

05/20/20

05/08/23

Wendy J. Weber, N.D., Ph.D., M.P.H.

This FOA encourages applications for a collaborating Data Coordinating Center (DCC) application that accompanies investigator-initiated, multi-site clinical trials (Phase III and beyond) applications submitted under PAR-18-696. The DCC application must be specific to the collaborating Clinical Coordinating Center (CCC) application. The objective of the DCC application is to propose a comprehensive plan that provides overall project coordination, and administrative, data management and biostatistical support for the proposed clinical trial. Both a DCC application and a corresponding CCC application must be submitted simultaneously for consideration by NCCIH.


*UG3/UH3 and U24 are companion announcements. Investigators must submit applications to both FOAs together. Investigators should be familiar with NCCIH’s policy on applications for large budget clinical trials.