Special Considerations for NIDA Funding Opportunities and Awards

If your recipient institution wishes to do a press release or is planning media outreach around your Notice of Award (NOA), please closely coordinate with the NIDA Press Office, which can be reached at media@nida.nih.gov. Please note that NIDA and NIH do not publicly discuss any funding or grant until it has been officially posted in NIH RePORTER, which is updated on a weekly basis. We therefore advise that recipients hold all public statements announcing your award (on social media, websites, through the press, etc.) until that time. 

In order to most effectively disseminate research results, advance notice should be given to NIDA that research findings are about to be published so that we may coordinate accurate and timely release to the media, by emailing the NIDA press office at media@nida.nih.gov.This information will be embargoed until the publication date. Any press materials issued by the recipient institution must also adhere to the Acknowledgment of Federal Funding Requirement (as specified in the NIH Grants Policy Statement).

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 here - NACDA Guidelines for Administration of Drugs to Human Subjects.

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 Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants

 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 for further details.

Applications proposing research on cannabis or its main psychotropic constituent delta-9-THC are required to measure and report results using a standard delta-9-THC unit in all applicable human subjects’ research.  The goal is to increase the comparability across cannabis research studies. A standard delta-9-THC unit is defined as any formulation of cannabis plant material or extract that contains 5 milligrams of delta-9-THC.  A justification should be provided for human research that does not propose to use the standard unit. Please see NOT-DA-21-049 for additional details.

Can NIH-supported researchers purchase or possess cannabis products containing > 0.3% delta-9-tetrahydrocannabinol from state-legal cannabis dispensaries for research purposes?               
NIH-funded researchers must possess a Schedule I research registration from the Drug Enforcement Administration to conduct research with cannabis products with more than 0.3% delta-9-tetrahydrocannabinol (THC) on a dry weight basis. Purchasing or handling such products without an appropriate registration is a violation of federal law and therefore a violation of the terms/conditions of an NIH research award. NIDA encourages grant applicants to contact the Drug Enforcement Administration with specific questions about whether the DEA would approve a Schedule I research registration for research using such cannabis products obtained from state-legal dispensaries.

Please see information below regarding research involving syringe services programs (SSPs) and drug paraphernalia distribution:

1. Prohibition on Purchase of Sterile Needles or Syringes and Restriction on Distribution of Sterile Needles or Syringes (Section 527 of Consolidated Appropriations Act, 2022 (Public Law 117-103)               
   “Notwithstanding any other provision of this Act, no funds appropriated in this Act shall be used to purchase sterile needles or syringes for the hypodermic injection of any illegal drug: Provided, that such limitation does not apply to the use of funds for elements of a program other than making such purchases if the relevant State or local health department, in consultation with the Centers for Disease Control and Prevention, determines that the State or local jurisdiction, as applicable, is experiencing, or is at risk for, a significant increase in hepatitis infections or an HIV outbreak due to injection drug use, and such program is operating in accordance with State and local law.”                
   Per the above statement, the grantee must ensure:

   • NIH funds are not to be used to purchase sterile needles or syringes for the hypodermic injection of any illegal drug.
   • If NIH funds are used for elements of a program other than making such purchases:
     • Your State or local health department, in consultation with the Centers for Disease Control and Prevention, has determined that the State or local jurisdiction, as applicable, is experiencing, or is at risk for, a significant increase in hepatitis infections or an HIV outbreak due to injection drug use; and 
     • The program is operating in accordance with State and local law.

   Please see listed legislative mandates in effect.

2. Jurisdictions Determined to be Experiencing or At-risk of Significant Increases in Hepatitis Infection or an HIV Outbreak Due to Injection Drug Use Following CDC Consultation               
   Please see CDC’s table of the jurisdictions that have consulted CDC and have been determined to have adequately demonstrated need for a SSP.
3. Federal Drug Paraphernalia Law               
   Per 21 U.S.C. § 863(a), “It is unlawful for any person to (1) sell or offer for sale drug paraphernalia; (2) to use the mails or any other facility of interstate commerce to transport drug paraphernalia; or (3) to import or export drug paraphernalia.” Section 863(d) defines the term “drug paraphernalia” as “any equipment, product, or material of any kind which is primarily intended or designed for use in manufacturing, compounding, converting, concealing, producing, processing, preparing, injecting, ingesting, inhaling, or otherwise introducing into the human body a controlled substance, possession of which is unlawful under this subchapter.” Examples of drug paraphernalia are provided in Section 863(d). Grantees are encouraged to reach out to their legal counsel with questions about this law.

Purpose/Background

The mission of the National institute on Drug Abuse (NIDA) is to advance science on drug use and addiction and apply that knowledge to improve individual and public health by supporting and conducting a wide range of clinical research. Effective clinical research relies on the ability of researchers to meet recruitment and retention goals. Recruitment and retention goals should include consideration, as appropriate, for inclusion and retention of women, members of racial and ethnic minority groups, and populations across the lifespan, in accordance with National Institutes of Health (NIH) policies.

NIDA strives for effective and efficient recruitment and retention of participants in all supported active clinical research, and this policy specifies the approach for monitoring recruitment and retention of participants in NIDA-supported clinical research to facilitate the achievement of research objectives and to ensure that NIDA remains a responsible steward of public funds.

NIH-funded research involving human subjects brings with it special considerations throughout the grant life cycle. The terms outlined here are in addition to and not in lieu of other NIH policies, including the Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan in the SF424 Application Guide and the Research Performance Progress Report (RPPR) which require annual reporting, at a minimum, per NIH reporting requirements for study enrollment.

Policy

The Recruitment and Retention Monitoring and Reporting of Clinical Research Awards Supported by the National Institute on Drug Abuse policy, as described in NOT-DA-23-033, specifies the requirement for the monitoring and reporting of recruitment and retention of participants in identified NIDA-supported contracts, grants and cooperative agreements that are active as of October 1, 2023 (FY2024) and support human subjects research (clinical research) as defined by the National Institutes of Health (NIH).

This policy applies to any active NIDA-supported clinical research which may include clinical trials, clinical research projects, and/or clinical research studies, regardless of size, to enable NIDA staff to more effectively monitor the recruitment and retention of participants.  NIDA-funded clinical trials will be subject to enhanced reporting of recruitment data (and retention data, at the discretion of the PO/COR) minimally twice per year. Identified NIDA-funded clinical research may be deemed by the Program Official (PO) or Contracting Officer’s Representative (COR) as requiring additional reporting and/or oversight. This policy ensures that investigators work with their PO/COR to establish recruitment and retention milestones of a clinical trial, clinical research project, and/or a clinical research study and establishes that progress must be reported based on the identified need by the PO/COR throughout the course of the award. This NIDA policy is aligned with the NIH Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®, Policy for the Enrollment of Participants in Clinical Trials.

In addition to the NIH reporting requirements, Principal Investigators (PIs) will be prompted by an automatically generated email from the NIDA Tracking Recruitment Assessment Query (TRAQ) system (from the address nidatraqnotifications@mail.nih.gov with subject line “NIDA TRAQ: …”) to update recruitment data within the NIH Human Subjects System (NIH HSS) and, as appropriate, retention data (see Procedures and Definitions below) within the NIDA TRAQ system. PIs can use their eRA commons username and password to enter these data.

Procedures

Planned enrollment data must be established in the Inclusion Enrollment Report (IER), by the PI, for all NIDA-supported clinical trials, regardless of size. Cumulative (actual) enrollment data for all active NIDA-supported clinical trials must be entered via the NIDA TRAQ system minimally twice per year through HSS, while enrollment data for all other identified NIDA-supported clinical research projects and/or clinical research studies must be entered at the frequency deemed appropriate by the PO/COR. Retention data (e.g., participants that complete and those that withdraw from the clinical trial, clinical research project, and/or the clinical research study) must be entered in the NIDA TRAQ system for all identified active NIDA-supported clinical research deemed by the PO or COR as requiring additional oversight.

Recipients can access the NIH HSS through the Human Subjects link in the RPPR or the eRA Commons Status page to update inclusion enrollment reports. For more information, see: https://www.era.nih.gov/erahelp/HSS_External/about_hss_external.htm?Highlight=milestone.

When developing milestones for recruitment and retention, consideration must be given, as appropriate and in accordance with NIH policies, to recruitment and retention of women, members of racial and ethnic minority groups, and participants of all ages. In addition, consideration must be given to the timing of milestones to ensure that recruitment and retention will take into consideration the necessary study start-up time and end with enough time remaining within the proposed project period to allow for necessary follow-up and analysis. The identified milestones, or targets, are to be cumulative in nature to eventually meet the total sample of the proposed study. The planned start and end dates for recruitment and cumulative recruitment targets are entered into the NIH HSS, and milestones should be updated at the time of the annual RPPR on the Human Subjects and Clinical Trials Information Form in HSS.

Retention data are entered into the NIDA TRAQ system, as needed. PIs can use their eRA commons username and password to enter these data.

• After the recruitment start date, and in accordance with the terms and conditions of the award, the PI submits this data through the NIH HSS.
• At any time during the project period, if modification of the total number of participants is needed based on scientific results or other unexpected events, the PI, via email from the AOR, notifies the assigned PO/COR and GMS/CMS (and other relevant regulatory bodies, as appropriate) and proposes an adjusted target number of participants. The requested changes will be evaluated, approved or disapproved by the PO/COR and GMS/CMS staff.
• If changes to the total number of participants are approved by the PO/COR and GMS/CMS, in accordance with the terms and conditions of the award, the PI submits modified recruitment targets via NIH HSS for approval by the PO/COR and continues to provide NIDA with cumulative actual recruitment updates in accordance with NIH policies or as deemed by the PO/COR if additional oversight is deemed necessary. For clinical trials, NIDA-approved (and other relevant regulatory bodies, as appropriate) modifications to trial protocols must be submitted to ClinicalTrials.gov.
• If changes to the interim (but not total) recruitment targets are needed, the PI must provide an explanation for the changes via email to the PO/COR and enter adjusted interim target numbers in the NIH HSS for PO/COR approval.
• The PO/COR will review the enrollment report, and, as necessary, will follow up with the PI to discuss recruitment challenges and efforts to improve enrollment. At the PO’s/COR’s discretion, a remediation plan and changes to the frequency in reporting may be implemented (e.g., every 1, 3, 6, months or any frequency that is deemed appropriate by the PO/COR).
• Once a PO/COR requests remediation, the PI will be prompted by an automatically generated email from the NIDA TRAQ system to update recruitment/enrollment data within the NIH HSS system and, as appropriate, retention data (e.g., participants that complete and those that withdraw from the clinical research project and/or the clinical research study) within the NIDA TRAQ system at the established frequency. If recruitment does not show adequate improvement, the NIDA team will determine viable options depending on the severity and duration of the recruitment shortfalls. If the deficiencies persist, the NIDA team will take further action, in accordance with NIH policy, which could include orderly phaseout, suspension, termination, or withholding of support.⁶ 

Responsibilities

• Principal Investigator(s) (PI), determines the preliminary and updates to actual recruitment milestones for the recruitment phase of the study, ensures recruitment plans for appropriate representation of women, minorities and participants across the lifespan in accordance with the approved application and NIH policies, submitting updated data on participant recruitment and enrollment at the required frequency via the eRA Commons, in the NIH HSS (typically when submitting the annual RPPR)  and ensures studies required to register at ClinicalTrials.gov are reported accordingly. Also, in the RPPR, the PI must update the Clinical Trial Milestone Plan for all studies involving clinical trials.  In addition, and upon request, the PI submits interim recruitment and retention reports into the NIH HSS and NIDA TRAQ systems, respectively, and, as appropriate, provides additional information via the Authorized Organization Representative (AOR) to NIDA officials regarding recruitment remediation efforts, as needed.
• NIDA Program Officials (POs) or Contracting Officer’s Representatives (CORs) review the proposed recruitment and retention milestones for appropriateness and feasibility, and request any additional information needed from the PI/AOR throughout the course of the award. The PO/COR, together with Grants Management (GM)/Contracts Management (CM) staff, will discuss and determine the terms and conditions of the award and inform the PI/AOR. In coordination with GM/CM staff, the PO/COR will monitor recruitment and retention and determine whether the recruitment goals are being met in accordance with the terms and conditions in the Notice of Award. PIs are expected to work with their POs/CORs should any modifications to approved targets or reporting frequency are needed.
• NIDA Grants Management Specialists (GMSs) and/or Contract Management Specialists (CMSs) ensure that NIDA actions comply with federal regulations and NIH policy. They are responsible for the business management and other non-programmatic aspects of the award,  receive official documents for inclusion in the official grant or contract files and specify the appropriate terms and conditions for the award notice.
   

Definitions

• Clinical Research: Research with Human Subjects that is: 1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanism of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies. (2) Epidemiologic and behavioral studies. (3) Outcomes research and health services research. Note: Studies falling under Exemption 4 for human subject research are not considered clinical research by this definition.
• Clinical Trial: A research study¹ in which one or more human subjects² are prospectively assigned³ to one or more interventions⁴ (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.⁵
  • Note: Basic Experimental Studies with Humans (BESH) are studies that meet both the definition of basic research and the NIH definition of a clinical trial. BESH therefore are subject to NIH clinical trials policies such as registration and results reporting. All BESH meet the NIH definition of a clinical trial, but not all clinical trials are BESH.
• Enrollment Data: Provides race and ethnicity data for the cumulative number of human subjects enrolled in an NIH-funded clinical research study since the protocol began.
  • Includes the estimated total number of participants to be enrolled (target number) or the actual total number of participants that are enrolled in the clinical study. Definition will be specific to each clinical research study and/or project and should be determined between the PI(s) and PO/COR of the respective study and/or project.
    • Note: "Enrolled" means a participant’s, or their legally authorized representative’s, agreement to participate in a clinical study following completion of the informed consent process. Potential participants who are screened for the purpose of determining eligibility for a study, but do not participate in the study, are not considered enrolled, unless otherwise specified by the protocol.
• Retention Data: 
  • Completers: Generally, individuals who completed the study, defined as those with primary study outcome assessment data available. Definition will be specific to each clinical research study and/or project and should be determined between the PI(s) and PO/COR of the respective study and/or project.
  • Dropouts: Generally, individuals who enrolled in the study who withdrew/were withdrawn prior to primary outcome assessment, with no primary outcome data available. Definition will be specific to each clinical research study and/or project and should be determined between the PI(s) and PO/COR of the respective study and/or project.   

Resources

• ClinicalTrials.gov
• NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research
• NIH Policy and Guidelines on Inclusion Across the Lifespan in Research Involving Human Subjects
• eRA commons
• NIH Human Subjects System
• NIH Grant Policy Statement
• NIH and Other PHS Agency Research Performance Progress Report (RPPR) Instruction Guide
• Federal Acquisitions Regulations

References

1. See Common Rule definition of research at 45 CFR 46.102 (l)
2. See Common Rule definition of human subject at 45 CFR 46.102 (e)(1).
3. The term “prospectively assigned” refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.
4. An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.
5. Health-related biomedical or behavioral outcome is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.
6. See NIH Grants Policy Statement 8.5.2 at https://grants.nih.gov/grants/policy/nihgps/nihgps.pdf  and Federal Acquisition Regulations Part 49 at https://www.acquisition.gov/far/part-49?searchTerms=Federal%20Acquisition%20Regulations%20Part%2049.