Consolidated Notice on NCCIH Clinical Trials Policies

Notice Number: NOT-AT-20-001

Key Dates
Release Date: October 8, 2019

Related Announcements

NOT-AT-19-011

PAR-18-113

PA-18-141

PA-18-159

PA-18-322

PA-18-323

PA-18-937

PA-18-939

PA-18-943

PA-18-944

PA-18-945

PA-18-946

PA-19-053

PA-19-055

PA-19-056

PA-19-091

PA-19-092

PA-19-200

PA-19-201

Issued by
National Center for Complementary and Integrative Health (NCCIH)

Purpose

The purpose of this Notice is to inform applicants that NCCIH accepts only mechanistic clinical trials when applications are submitted using NIH Parent Announcements and Funding Opportunity Announcements (FOAs) listed in the “Related Announcements” section. Clinical trials that propose to test the safety or demonstrate efficacy or effectiveness of an intervention will only be accepted using the NCCIH-issued FOAs (PAR-18-662 or PAR-18-696). NOT-AT-19-011 previously identified that NCCIH only accepts Clinical Trial applications proposing mechanistic studies for the “Parent Research Project Grant (Parent R01 Clinical Trial Required)” (PA-19-055).This Notice reminds applicants of this continued policy and also extends the NCCIH clinical trials policy to FOAs that are Clinical Trial Required NCCIH FOAs for Mechanistic Studies; and Clinical Trials Optional NCCIH FOAs for Fundamental Science studies (PA-18-323, PAR-18-322, PAR-18-113).

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

Studies that are designed to test the safety or demonstrate the efficacy/effectiveness of an intervention should be submitted under the appropriate NCCIH Clinical Trial FOA. Please see NCCIH’s Clinical Trials Funding Opportunity Announcements web page for further information.

The following types of clinical trials are not intended to be supported by NCCIH under parent announcements or mechanistic clinical trial (optional or required) announcements:

  • Early-stage trials of complementary or integrative treatment approaches in humans that aim to test feasibility for a future efficacy or effectiveness study of clinical outcomes.
  • Studies to develop or conduct tests of the clinical efficacy/effectiveness of treatments (e.g. analysis of effect size and/or statistically significant difference on clinical outcomes).
  • Studies that have safety, clinical efficacy, clinical management, and/or implementation as its principle aim.

Examples of mechanistic clinical trials that are allowable under parent announcements include, but are not limited to:

  • Studies in which a manipulation (physiological or behavioral) is used to answer basic science questions about normal physiological function.
  • Studies to develop, validate, and/or apply novel measures of biochemical, physiological, and neural circuits contributing to healthy behaviors in humans as well as biomarkers of physiological processes.
  • Studies that use an experimental manipulation (e.g., natural product, mind and body intervention, or cognitive task activating a specific neural circuit) in order to understand normal functioning or the pathophysiology of a disorder, but do not aim to demonstrate efficacy on clinical outcomes.
  • Studies that involve the prospective use of complementary or integrative interventions (e.g., natural product, behavioral, mind and body intervention, other therapeutic approaches) with demonstrated efficacy, where the intent is to obtain biospecimens (e.g., blood, patient-derived induced pluripotent stem cells) to identify genetic risk associations, novel biomarkers, examine the disease process, or characterize mechanisms of therapeutic response.
  • Studies in which a complementary or integrative intervention with demonstrated efficacy for that population is being studied to understand mechanisms of response, non-response, or risk of adverse effects of the efficacious intervention.

NCCIH strongly encourages applicants to consult with NCCIH Program Officials prior to submitting an application with human subjects to determine which available FOA would best support the proposed research.

This Notice supersedes the prior NCCIH Policy Notice, NOT-AT-19-011, and applies to subsequent reissues of the Funding Opportunity Announcements mentioned above in the “Related Announcement” sections.

Inquiries

Please direct all inquiries to:

Wen G. Chen, MMSc, PhD
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-451-3989
Email: chenw@mail.nih.gov