Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Approximately 40% of older Americans report living with chronic pain. Of these, 60-70% describe pain in multiple body sites, and over 60% describe multiple types of pain. Leading causes of chronic pain in this population include musculoskeletal conditions (e.g., arthritic and degenerative spine disease, myofascial syndromes), neuropathies (e.g., secondary to herpes zoster, diabetes, radiculopathy, chemotherapy), cancer-related pain, and headaches. Chronic pain is associated with substantial morbidity due to impaired mobility, activity avoidance, depression, anxiety, sleep impairment, substance use, and social isolation. Suicidal ideation among individuals with chronic pain is three times higher than those without chronic pain. Chronic pain also incurs a substantial economic burden with regard to healthcare utilization, durable medical equipment, premature disability claims, and numerous opportunity costs.

Treatment of pain in later life is complex and often inadequate. Acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and atypical analgesics are the mainstays of pharmacologic treatment. However, limited efficacy and/or risk of adverse effects limits their use in older adults. Topical analgesics and non-pharmacologic therapies like cognitive behavioral therapy, physical activity regimens, acupuncture, and electrical stimulation may avoid the pitfalls of systemic pharmacologic therapy for older adults, but they have variable efficacy and uptake.

A potential novel approach to treatment of chronic pain in older adults involves psychedelic-assisted therapy (PAT). Research with psychedelics was inspired by millennia of Indigenous experience incorporating sacred plant medicines in ceremonial healing practices. In the mid-20^th century, psychedelic-assisted therapy developed as an emerging treatment strategy for a variety of important clinical conditions. PAT uses psychedelic agents in combination with psychological support or psychotherapy in a conducive environment (“set and setting”). Evidence for the efficacy of PAT has been particularly notable in depression, anxiety (especially existential distress), post-traumatic stress disorder (PTSD), and substance use disorders, among other indications.

For the purposes of this NOFO, the term psychedelic includes “classic” psychedelics, typically understood to be 5-HT2 agonists such as psilocybin, N,N-Dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and mescaline, as well as entactogens or empathogens such as methylenedioxymethamphetamine (MDMA). Synthetic analogs of these agents are also included. Cannabis, ketamine, and their related products are not considered psychedelic agents for the purpose of this NOFO.

Clinically authorized PAT will likely become widespread over the next several years. The United States Food and Drug Administration (FDA) has granted breakthrough therapy status to a select number of psychedelic agents, and is actively developing regulatory frameworks for approval of these compounds, which is anticipated in the near future. The FDA released draft guidance on psychedelic drug considerations for clinical investigations in June 2023. Several states and municipalities across the country have enacted legislation, or have pending legislation, to decriminalize or legalize psychedelic agents. As a result, clinical use of psychedelic agents will likely outpace the evidence base for their safety and efficacy across heterogeneous populations seeking these treatments. Although previous and ongoing trials of PAT have included limited numbers of older adults who have tolerated treatment well without significant adverse effects, more focused safety and efficacy studies in older adults are needed.

Research Objectives

This NOFO will support a clinical trials network involving multiple institutions to collect safety and early efficacy data in defined groups of older adults living with specific chronic pain conditions through a biphasic mechanism. The first phase will involve safety and efficacy studies in healthy older adults, and the second phase will involve expanded safety and efficacy studies in older adults with chronic pain conditions. This funding structure is expected to lead to a higher level of collaboration, planning, and harmonization than would be possible through multiple individually funded grants. Studies supported by this NOFO should provide an evidence base to inform safe and efficacious PAT across heterogeneous populations of older adults living with chronic pain.

PAT involves psychological support, behavioral therapy, or psychotherapuetic approaches complementing psychedelic administration. Given the variety of interventional elements of PAT, the consortium should conduct multiple studies serially and/or in parallel as appropriate to optimize safety and therapeutic effects of PAT for the populations and conditions involved. These elements may include, but are not limited to, the following:

• Psychedelic agent. Different agents may have differential effects, pharmacokinetic properties, temporal profiles, and other characteristics. The types of psychedelic agents acceptable for support through this NOFO are noted above. Psychedelic agents must have reliable sourcing and quality assurance.
• Dosing strategy. Investigators may test single or multiple doses along with variations in timing interval between doses. “Booster” doses, administered weeks or months after initial dosing, may be considered. Concomitant administration of medications intended to counteract potential side-effects of psychedelics, such as anti-emetics or anti-hypertensives, may be considered.
• Preparation and integration modalities. A variety of behavioral therapeutic modalities may be tested as part of the “set” component of PAT. These may include cognitive-behavioral strategies, acceptance and commitment therapy, motivational enhancement, mindfulness, guided imagery, and other approaches. The consortium is strongly encouraged to use, adapt, and/or develop manualized behavioral therapeutic approaches to increase likelihood of harmonization across studies and successful implementation in practice settings.
• Therapeutic environment. Investigators may test variations in the “setting” through which preparation, dosing, and integration sessions are implemented. These include individual, group, in-person, and/or remote settings; indoor and/or outdoor settings; various components within them including visual, auditory, tactile, olfactory, and other sensory elements; and accommodations for participants with chronic pain, mobility limitations, and/or disability.
• Clinical outcomes. Measures should include pain-related outcomes such as pain intensity, pain interference, pain acceptance, fear avoidance, willingness to engage in physical therapy, and other pain-related behaviors; additional relevant clinical outcomes such as mood, physical function, cognitive function, quality of life, sleep, drug usage (both prescription and non-prescription), and non-pharmacologic treatments.
• Other outcomes. Studies should include measures of participants’ subjective experience to elucidate its relationship with therapeutic effects; measures of blinding of participants and study staff to control for expectancy effects; qualitative and quantitative measures of feasibility (e.g., recruitment and retention), acceptability, tolerability, willingness to participate, and possible stigma associated with participation; measures of participant characteristics that may influence therapeutic effects, such as personality measures, subjective well-being, self-efficacy, life-orientation, and self-compassion.
• Safety and adverse events. Studies must include standardized adverse event collection and reporting. Older adults may be more likely to experience certain adverse events compared to younger participants that have populated most published PAT studies to date. Some participant experiences that are typically considered adverse events, such as hallucinations and altered mood, may be expected with PAT. As such, the consortium may consider developing evidence-based approaches to inform adverse event reporting for future PAT research.
• Trial design and analysis. Investigators may employ various comparators such as inert placebo, active placebo, or low-dose psychedelics; parallel arm, cross-over, factorial, adaptive, and other designs; and innovative statistical approaches to address heterogenous participant populations and other study factors.

In addition to conducting multiple clinical trials to generate safety and early efficacy evidence, the consortium may also conduct observational studies, ancillary studies to ongoing trials, and secondary analyses of existing datasets where available to inform the overall goal of this initiative. Investigator meetings are also appropriate to identify knowledge gaps and research opportunities, establish core outcome sets, develop a roadmap for additional PAT research needs, and other consensus-building activities. Additionally, the consortium should include dissemination activities, such as for best practices of PAT research and implementation in older adult populations.

Investigators must ensure heterogeneity among study participants including geographic, racial, ethnic, sex, and gender, and study materials and interactions must be tailored to the backgrounds and cultures of study participants. Additionally, investigators should consider design elements that will facilitate translation of best practices and equitable access across heterogeneous populations in future practice settings.

Applicants should propose a Coordinating Center to organize all activities of the consortium. Applicants may choose to consolidate clinical, data, and other coordinating functions at one institution or to distribute these functions among multiple institutions within the geographically diverse consortium. 

UG3/UH3 Exploratory/Developmental Phased Award

This NOFO uses the  UG3 / UH3 activity code. Each phase is structured as follows: 

The UG3 Exploratory/Developmental Phase (Phase 1)

The UG3 phase is the first phase. This phase provides up to two years of support for exploratory/developmental activities. This phase should involve preliminary studies in healthy older adults across a broad age range to evaluate safety, pharmacokinetic, and pharmacodynamic properties of psychedelic agents. Additionally, the UG3 phase should involve preliminary testing of study elements (examples of which are described above) that will inform further development and testing in the UH3 phase (phase 2). 

The UH3 Implementation Phase (Phase 2)

The UH3 phase is the second phase. This phase provides up to three years of support for implementation activities. UH3 studies will include expanded safety and efficacy studies in older adults living with chronic pain conditions such as cancer, musculoskeletal pain, peripheral neuropathy, post-herpetic neuralgia, and recurring headaches. This phase must include participants living with non-contraindicated co-occurring conditions representative of real-world older adults; for example, depression, anxiety, PTSD, diabetes, age-related cognitive impairment, chronic kidney disease, and fatty liver disease. Phase 2 studies must incorporate appropriate designs and adequately powered analyses to account for the expected heterogeneity of enrolled participants. 

Both Phases

In both phases of the award, participants across a broad range of ages must be included, with particular attention to strata at the upper age range (i.e., 75-80 years, and 80+ years old). Unless deliberate efforts are made to enroll individuals from these age groups, they will likely be underrepresented or omitted altogether. 

Both phases must ensure that participant risk:benefit is justified for all studies. Studies must focus on human populations; animal studies are outside the scope of this NOFO.

Prior to each trial in each phase, the awardee must have satisfied all regulatory and infrastructural requirements for PAT studies including Drug Enforcement Agency (DEA) licensure, Investigational New Drug (IND) approvals, Institutional Review Board (IRB) approvals, psychedelic agent sourcing, and quality assurance.

Transition from the UG3 to UH3 Phase

Attainment of recipient-specified milestones in the UG3 phase will be required to proceed to the UH3 phase of the award. The recipient must submit a transition package no less than 3 months prior to the end of the UG3 phase that describes progress made vis-à-vis the milestones and plans for the UH3 phase. Specific information of required materials will be provided after award. NIA program staff will evaluate the transition package to determine whether to award the UH3 phase. Proposed milestones must be specific, measurable, achievable, relevant, and time-bound (SMART) goals. Examples of milestones include, but are not limited to:

•  Attainment of infrastructural needs for PAT studies, such as DEA license, IND approvals, IRB approvals, psychedelic agent sourcing and quality assurance
•  Completion of pharmacokinetic and pharmacodynamic studies in healthy older participants
• Demonstrated safety outcomes in healthy older adult populations
• Optimal dosing strategies of psychedelic agent(s)
• Optimal parameters for set and setting approaches
• Adequate enrollment of age strata across the older age spectrum
• Adequate enrollment of participants from diverse backgrounds and heterogeneous populations

Project Oversight

Several bodies will be established to oversee the awarded consortium.

An External Advisory Panel (EAP) will be established to review the consortium’s progress in meeting its aims and provide recommendations to the PIs. NIA will appoint members of the EAP with input from the study PI(s). Membership may include study investigators and independent scientific experts in areas appropriate to the project.

NIA will appoint a Data and Safety Monitoring Board (DSMB) with expertise relevant to proposed studies.

A Steering Committee comprised of the study PI(s), NIA program officer, and NIH project scientist(s) will be established as part of this cooperative agreement award.

See Section VI Cooperative Agreement Terms and Conditions for more information about the Steering Committee. 

Non-Responsiveness Criteria

The following types of applications will be considered non-responsive to this NOFO and will be administratively withdrawn prior to scientific peer review:

• Applications that focus on cannabis, ketamine, or their related compounds
• Applications that do not involve behavioral therapy, psychological support, or psychotherapeutic approaches complementing psychedelic administration
• Applications that do not address both UG3 and UH3 phases
• Applications proposing animal studies

Additional information

A pre-application webinar will be held to discuss this NOFO and answer prospective applicants' questions. Information about the pre-application webinar and answers to frequently asked questions regarding this NOFO, can be found on NIA's webpage for this NOFO. Applicants are encouraged to check this site periodically, as it will be updated regularly.

NIA’s Commitment to Inclusivity

NIA is committed to supporting and conducting research on aging that improves the health and well-being of all people. Therefore, NIA will prioritize the advancement of science that appropriately represents, in terms of race, ethnicity, sex, age, and comorbidity, the population affected by the condition being studied. Applicants should ensure as applicable that they 1) include proposed planned enrollment tables representative of the population affected by the disease/condition, and 2) are appropriately inclusive of NIA Health Disparities Framework priority populations; participants across the lifespan; as well as other populations experiencing health disparities.

Clinical Research Operations Management System

NIA uses a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. NIA Clinical Research Operations & Management System (CROMS) is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. NIA investigators of grants, contracts, and cooperative agreements that are active as of July 1, 2021, including clinical trials funded as pilots, exploratory studies, or other projects through this Consortium, and support human subjects research as defined by the DHS HHS OHRP regulations at 45 CFR 46 will be required to interact with and use existing and future components of CROMS as required by NIA throughout the lifecycle of the grant, as described in NOT-AG-23-017. Data to be submitted to NIA CROMS includes those elements reported in the standard NIH requirement annual progress report (GPS 4.1.15.7). Details regarding the standard operating procedures for CROMS can be found on the NIA CROMS website.

When applicable, all NIA grantees must ensure:

1. The study’s Informed Consent Document (ICD) lists “The National Institutes of Health (NIH) and its authorized representatives” as one of the organizations that may look at or receive copies of information in participants’ study records. According to DHS HHS OHRP 45 CFR 46 §46.116, all ICDs must contain “A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained.” If using the NIA informed consent template, please see Section 6: Statement of Confidentiality. 

2. An assigned NIH ClinicalTrials.gov identifier (NCT number) is reported in its respective CROMS study record within three months after assignment, and the reporting of final enrollment data to CROMS is consistent with final enrollment data reported in ClinicalTrials.gov.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

Study teams must have demonstrated experience to successfully achieve the goals of this NOFO, including expertise in psychedelic-assisted therapy, management of chronic pain, geriatrics/aging and multimorbidity, and management of multi-site clinical trials.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

NIA Psychedelic Research
Email: NIAPsychedelicResearch@nih.gov

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

The application must describe how the proposed applicant institutions will provide a conducive research environment, such as previous successful DEA Schedule I licensure, IND approval(s) for psychedelic agents, and other infrastructural needs for PAT research.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

The application must describe the investigators' collective experience to successfully achieve the goals of this NOFO, including expertise in psychedelic-assisted therapy, management of chronic pain, geriatrics/aging and multimorbidity, and management of multi-site clinical trials.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

Applicants should budget for at least yearly meetings of the External Advisory Panel, at least semi-annual meetings of the DSMB, and regular meetings of the Steering Committee. These meetings may be in-person and/or virtual. The NIA expects up to a 5-member DSMB with honoraria up to $1000/member/year. Budgeting should also include study staff time for scheduling DSMB meetings and distributing and collecting DSMB-related materials from study sites.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

The Specific Aims page must describe aims for both the UG3 and UH3 phases.

The 12-page Research Strategy must include descriptions of both UG3 and UH3 phases, as well as a list of milestones (written as SMART goals) that must be achieved by the end of the UG3 phase to warrant transitioning to the UH3 phase. Both phases should describe a series of clinical trials involving varying permutations of intervention elements to achieve the overall goal of this initiative. 

For both UG3 and UH3 phases, applicants must describe plans to enroll participants across a broad range of ages including strata at the upper age range and from heterogeneous backgrounds and populations across geographic, racial, ethnic, sex, and gender representation. In addition, study materials and interactions must be tailored to the backgrounds and cultures of study participants. Both phases must ensure that participant risk:benefit is justified for all studies.

For the UH3 phase, applicants must describe plans to include participants living with non-contraindicated comorbidities representative of real-world older adults; e.g., depression, anxiety, PTSD, diabetes, age-related cognitive impairment, chronic kidney disease, and fatty liver disease. Phase 2 studies must incorporate appropriate designs and adequately powered analyses to account for the expected heterogeneity of enrolled participants. Applicants should describe how they will prioritize pain conditions to be studied in the UH3 phase.

Prior to each trial in each phase, the awardee must have satisfied all regulatory and infrastructural requirements for PAT studies including Drug Enforcement Agency (DEA) licensure, Investigational New Drug (IND) approvals, Institutional Review Board (IRB) approvals, psychedelic agent sourcing, and quality assurance.

Eligibility Criteria

Without duplicating information in the Human Subjects and Clinical Trails form, applications in response to this NOFO must provide rationale that eligibility criteria encourage diversity across multiple factors such as age, race, ethnicity, sex, gender, education, socioeconomic status, geographic location, comorbidities, cognitive status, and other populations experiencing health disparities to diversify and increase participation in clinical trials. The goal is for clinical trial participants to adequately reflect the diversity of the real-world population, so that researchers can determine whether the variables being studied affect women or members of any racial and ethnic population group in accordance with the NIH Revitalization Act of 1993.

Study teams must demonstrate that they have considered inclusive practices including proposed planned enrollment tables representative of the population affected by the disease/condition. Where applicable, study teams should also demonstrate that they have critically evaluated which eligibility criteria from an earlier phase trial should be carried forward into a later phase trial. The eligibility criteria section must:

• Describe how the study results generalize to the wider patient population with this disease/condition.
• Explain how the rationale for selected eligibility criteria justify the level of restriction in the study compared to clinical practice.
• Provide evidence that the eligibility criteria support the proposed research and encourage diversity across multiple sociodemographic factors.

Recruitment and Retention Plan

Without duplicating information in the Human Subjects and Clinical Trails form, applications in response to this NOFO must propose innovative and proactive recruitment strategies for involving historically underrepresented populations to ensure more diverse and inclusive representation as applicable and justified by the scientific goals. An emphasis on diversity across multiple factors such as age, race, ethnicity, sex, gender, education, socioeconomic status, geographic locations, comorbidities, cognitive status, and other populations experiencing health disparities is encouraged. Recruitment and Retention Plans should demonstrate an understanding of the participant burden involved in research participation and strategies for minimizing this burden, as well as leveraging community partners and outreach efforts. The Recruitment and Retention Plan must:

• Describe potential barriers to participation and plans to minimize these barriers.
• Describe a detailed plan for the recruitment of underrepresented populations and a plan to leverage existing relationships with and/or conduct outreach to diverse community groups.
• Describe staff training to be sensitive to cultural, racial, and ethnic differences. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding. 

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Retaining custody of, and have primary rights to, the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• Designing the details of the Consortium funded through this NOFO and retaining primary responsibility for performance of the activities.
• Determining approaches, designing, and setting project milestones, and implementing the project plan for the Consortium.
• Participating in Steering Committee meetings. 
• Providing integrative, organizational, and logistical support for the entire program, including tracking, scheduling, and facilitating in-person, hybrid, or virtual work group meetings, Steering Committee meetings, and other proposed recurring meetings or conference calls, including preparing concise minutes or summaries of meetings with clear action items for distribution.
• Cooperating with all Consortium members in the publication and dissemination of program results and the eventual release of methods, tools, results, research protocols or approaches, and other resources to the scientific and healthcare communities.
• Considering the External Advisory Panel's (EAP's) input regarding implementation of study aims, as well as additions or changes to content and methods during the execution of the cooperative agreement(s). EAP input is not binding on the PD(s)/PI(s) who retain primary responsibility for scientific direction and implementation.
• Responding promptly and cooperatively to requests for information or input from NIA.
• Retaining custody and having primary rights to the data and software at the recipient institution developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and goals of this program. All research, data (it is expected the Consortium will have a Data Management and Sharing Plan that will protect human subjects), and resources generated must have broad availability through a public-facing website to facilitate collaboration, reuse, and replication, as appropriate and consistent with achieving the goals of the program.
• Ensuring that all web resources developed are transferred to any subsequent award recipient should the program be continued beyond the project period.
•  

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• An NIA Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIA Program Official will approve all major stages of the project and all new major additions/changes to planned activities. The NIA Program Official is an ex officio member of the EAP and will approve membership and agendas of the EAP.
• In addition to the NIA Program Official, NIH program staff from participating ICOs will be named as Project Scientists for the Consortium. NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NIH Project Scientists will assist in refining study objectives and activities.
• NIA/NIH staff may participate and/or attend in work groups, implementation teams, and committees, including the Steering Committee and DSMBs, as appropriate. 
• NIA/NIH staff may serve as resources for, or interface with, other ongoing NIH activities that may be relevant to the activities in this Consortium to avoid duplication and facilitate collaboration and communication in overlapping areas.

Areas of Joint Responsibility include:

• Determining the process of setting Consortium priorities, deciding optimal administrative and governance approaches, and contributing to the adjustment of approaches as warranted.
• Developing agendas for Steering Committee meetings and annual research and business meetings.
• Participating in ongoing conference calls among PD(s)/PI(s), NIH Project Scientist(s), and/or other NIH program staff, as scheduled and agreed upon.
• Considering the Steering Committee and the EAP input for modifying the Consortium’s focus to accommodate new scientific opportunities and directions.
• Sharing and reviewing annual progress among components of the Consortium and with external stakeholders. 

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (Responsibility/Qualification in SAM.gov, formerly FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

NIA Psychedelic Research
Email: NIAPsychedelicResearch@nih.gov

Sekai Chideya-Chihota, MD, MPH
National Center for Complementary and Integrative Health (NCCIH)
Phone: 240-552-2994
Email: sekai.chideya@nih.gov

Ramesh Vemuri, PhD
Telephone: 301-496-9666
Email: ramesh.vemuri@nih.gov

Luchelle Stubbs
Email: luchelle.stubbs@nih.gov

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: debbie.chen@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.