Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required) is sponsored by National Institute on Aging (NIA), NIH. This NOFO invites applications for bundled independent protocols for phase 1 and phase 1b/phase 2a clinical trials to streamline early-stage evaluation of promising pharmacological interventions for AD and ADRD.

PAR-25-226: Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Funding Opportunity Title Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to invite applications that bundle independent protocols for phase 1 clinical trials with phase 1b/phase 2a clinical trials to streamline the early-stage evaluation of promising pharmacological interventions for Alzheimer's disease (AD) and AD-related dementias (ADRD).

Candidate interventions evaluated through this program, which can include small molecules or biologics for example, must engage non-amyloid/non-tau mechanisms and aim to address cognitive and/or neuropsychiatric symptoms in individuals across the spectrum, from pre-symptomatic to more severe stages of disease. This NOFO uses a phased award activity code.

Applications must include prespecified, go/no-go safety and tolerability milestones that must be met to advance from phase 1 to latter stages of clinical development. Funding Opportunity Goal(s) To encourage biomedical, social, and behavioral research and research training directed toward greater understanding of the aging process and the diseases, special problems, and needs of people as they age.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions 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 Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 The biggest risk factor for Alzheimer's disease (AD) is age.

AD is the most common cause of dementia in those aged 65 and older. As populations age worldwide, this disorder, as well as AD-related dementias (ADRD), will reach epidemic proportions even in best-case scenarios, with an enormous human and economic burden.

Dementia is one of the most persistent and devastating neurodegenerative diseases because it eventually leads to widespread brain and neuropsychological dysfunction, and the loss of the ability to interact with others and to function independently. It is estimated that over 6 million Americans aged 65 and older are living with AD today. This number could grow to 12.

7 million by 2050. From an economic perspective, estimates suggest AD/ADRD cost society over $355 billion in 2021. These human and economic costs are untenable, and it is critical to accelerate the development of interventions to prevent, slow, or cure AD.

Recent biomedical advances inspire optimism for the path ahead. In 2022, the Food and Drug Administration (FDA) approved the disease modifying anti-amyloid agent, Aduhelm, for the treatment of AD via the accelerated approval pathway. Subsequently, and also via the accelerated approval pathway, the FDA approved the disease modifying anti-amyloid agent, Leqembi, in early 2023.

Leqembi is the first medicine to demonstrate a modest yet significant slowing of cognitive decline. Together, these medications represent important advancements in the ongoing fight to effectively treat AD. Nevertheless, additional efforts remain necessary to tackle the devastating effects of AD/ADRD.

To meet the congressionally mandated goal of preventing and treating AD/ADRD, it is critical that we have efficient mechanisms to fund clinical trials pursuing a myriad of therapeutic targets and approaches to prevent, delay, and treat AD/ADRD. This NOFO directly addresses a gap noted in the 2021 NIH AD Summit and the corresponding new AD/ADRD Milestone 4.

Y by accelerating the early clinical development of novel (non-amyloid/non-tau) candidate therapeutic agents (small molecules/biologics). The purpose of this NOFO is to invite applications that bundle independent protocols for phase 1 clinical trials with phase 1b/phase 2a clinical trials to streamline the early-stage evaluation of promising pharmacological interventions for AD/ADRD.

Candidate interventions evaluated through this program, which can include small molecules or biologics for example, must engage non-amyloid/non-tau mechanisms and aim to address cognitive and/or neuropsychiatric symptoms in individuals across the spectrum, from pre-symptomatic to more severe stages of disease.

This NOFO supports the evaluation of promising novel pharmacological interventions for AD/ADRD by facilitating the timely, successive progression of candidates from phase 1 clinical trials to phase 1b/2a trials based on prespecified, go/no-go safety and tolerability criteria.

Candidates, including small molecules and biologics evaluated through this program, must engage non-amyloid/non-tau mechanisms and aim to address cognitive and/or neuropsychiatric symptoms in individuals across the spectrum from pre-symptomatic to more severe stages of disease. The UG3 mechanism will be used to plan and execute phase 1 studies.

The UH3 mechanism can support additional Phase 1-level studies but is primarily intended to support the execution of the phase 2a clinical trial. Transition to the UH3 will depend on successfully reaching agreed-upon milestones and go/no-go criteria.

This NOFO invites clinical trial applications that propose activities including, but not limited to, the following focus areas: Evaluation of safety and pharmacokinetics of novel therapeutics in healthy volunteers or the target population, as appropriate Projects directed at a phase I trial that will be able to reference prior Good Laboratory Practice (GLP) toxicology studies (e.g., repeat dose toxicology in rodents and large animals, genotoxicology, human Ether-à-go-go-Related Gene (hERG) and safety pharmacology) Good manufacturing practice (GMP) of drug substance/product needed for the proposed clinical trials Preparation of protocols, and acquisition of regulatory approvals Evaluation and optimization of dose, formulation, safety, tolerability, or pharmacokinetics of an intervention to enable FDA required (cite guidance or provide documentation from FDA with their specific request) activities for start of phase 2a in healthy volunteers, or the target population Aims focused on the acquisition and analysis of biomarkers Evaluation of whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, target engagement, dose-response trends, pharmacodynamic response) in a human “proof of concept” trial Examples of interventions for evaluation that are appropriate for this NOFO include, but are not limited to, the following: Pharmacological interventions, including small molecules and biologics that target eradication or progression of disease Pharmacological interventions, including small molecules and biologics that target disease symptomatology including neuropsychiatric symptoms Repurposed drugs that have promise for AD/ADRD treatment, such as chemotherapeutic agents or drugs for insulin dysregulation/diabetes This NOFO supports phase 1, phase 1a, phase 1b, food effect studies, and phase 2a clinical trials.

Applications should aim to generate data that informs further clinical development of the proposed intervention. The earliest studies should be designed to provide important initial information regarding the intervention (e.g., safety, tolerability, dosing).

Phase 1 studies may include randomization and blinding and must yield data that allows for a clear go/no-go decision (typically based on safety/tolerability data) regarding whether the intervention should proceed to latter stages of evaluation. Participants within trial cohorts must be heterogeneous. Timely access to trial data and associated biosamples to the broader research community is required.

This NOFO is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy; although, where appropriate, exploratory studies of preliminary efficacy can be a secondary aim. Applications to implement definitive efficacy trials (e.g., Phase 3 trials of drugs/biologics or pivotal trials) will be considered nonresponsive to this NOFO.

Applicants are strongly encouraged to consult with NIA Program staff as plans for an application are being developed (see Section VII, Agency Contacts) no later than 12 weeks prior to the anticipated application submission date. This early contact will provide an opportunity to clarify NIA processes and guidelines, as well as to discuss how to develop an appropriate project timeline and milestone plan, which is subject to peer review.

NIA Program staff are also available to discuss strategies for recruitment and inclusion, including the recruitment and inclusion of women and members of racial and ethnic minority groups. UG3/UH3 Exploratory/Developmental Phased Award This NOFO uses the UG3/UH3 phased award activity code. The UG3/UH3 application must be submitted as a single application at the time of the initial application.

Applications must include prespecified, go/no-go safety and tolerability milestones that must be met to advance from phase 1 (UG3) to latter stages of clinical development (UH3). During the UG3 phase, researchers will plan and execute phase 1 studies. The UG3 phase will permit both scientific and operational planning activities.

During the UH3 phase, additional phase 1-level studies maybe supported, but this phase is primarily intended to support the execution of the phase 2a clinical trial. The UH3 phase of the award will support the clinical trial of the small molecules and biologics. Transition to the UH3 will depend on successfully reaching agreed-upon milestones and go/no-go criteria .

Only UG3 projects that have met scientific milestones and feasibility requirements will be approved to transition to the UH3 phase. Clinical Research Operations Management System: NIA utilizes 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 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. Non-Responsiveness Criteria (Applications Not Responsive to this NOFO) The following types of applications will be considered non-responsive and will be withdrawn prior to review Applications to implement definitive efficacy trials (e.g., Phase 3 trials of drugs/biologics or pivotal trials) Applications that only propose UG3 or UH3 activities Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this NOFO. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period. The proposed project period for the UG3 phase must not exceed 2 years.

The total duration of the UG3/UH3 phases combined must not exceed 5 years. 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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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 the 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.

Eligible Individuals (Program Director/Principal Investigator) 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.

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. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility 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 Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission 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.

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.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. 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. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: This NOFO encourages the submission of applications for the clinical testing of novel candidate therapeutics engaging non-amyloid/non-tau mechanisms (small molecule and biologics), as well as for repurposed drugs.

Candidate interventions evaluated through this program, which can include small molecules or biologics for example, must engage non-amyloid/non-tau mechanisms and aim to address cognitive and/or neuropsychiatric symptoms in individuals across the spectrum, from pre-symptomatic to more severe stages of disease. Investigators are strongly encouraged to incorporate pharmacodynamic biomarkers in the design.

Investigators are also expected to collect and store blood and other biosamples for future genomic and other 'omic' analyses aimed at interrogating treatment responsiveness and examining predictors of decline and progression. Additional guidance for this section is provided below, based on the clinical trial phase.

The application must describe the specific aims for each of the two phases (UG3 and UH3) on the single Specific Aims attachment. Include headers indicating the UG3 specific aims and the UH3 specific aims.

UG3 Phase (Phase 1/1a Studies) Applications for therapeutic agents against known target(s) are expected to include information on the mechanism of action for the therapeutic agent, information regarding the target's role in disease pathogenesis and clinical relevance of the target, and information on the predicted optimal disease stage (e.g. pre-symptomatic, Mild Cognitive Impairment, mild, moderate or severe AD) to engage the target from preclinical development studies.

Applicants proposing a multi-target therapeutic should summarize the available information on the pathogenic pathways that the agent engages and provide a strong clinically-relevant rationale for this approach.

If the specific molecular target of the therapeutic agent is not known, applications should summarize what is known about the agent's mechanism of action and whether the agent engages a disease-relevant pathophysiological process. The application must include prespecified, go/no-go safety and tolerability milestones that must be met to advance from phase 1 (UG3) to latter stages of clinical development (UH3).

Transition to the UH3 will depend on successfully reaching agreed-upon milestones and go/no-go criteria . Only UG3 projects that have met scientific milestones and feasibility requirements will be approved to transition to the UH3 phase. UH3 Phase (Phase 1b/2a Studies) If available, applicants must provide evidence of safety from earlier phase clinical trials and must include further evaluation of safety in the proposed trial design.

Applications containing phase 2a clinical trials must be designed as proof of mechanism/target engagement/proof of concept studies. For applications proposing phase 1b or food effects studies in the UG3 phase, applicants should also provide evidence of safety from earlier phase clinical trials and should include further evaluation of safety in the trial design.

Significance and Biological Relevance Applications should describe the significance of the proposed Phase 1 and Phase 2 clinical trials in the context of the status of therapeutics for the disease and the costs and benefits of the proposed study intervention. The application must state how the trial will test the hypotheses proposed and how the results of the trial (positive or negative) will advance the field.

The application must summarize plans for future clinical development of the intervention in the event the exploratory trial yields promising results and explain why the proposed exploratory trial is necessary to inform the design of a subsequent clinical trial for efficacy.

This should include details about the clinical indication (e.g., disease stage, target population), the plan for use of biomarkers in the course of further clinical development (i.e., biomarkers for target engagement, responsiveness to treatment, and/or tracking of disease progression), and a clinical development timeline. The application must describe how the proposed intervention will likely be an improvement over existing therapies.

The application must detail the major findings of the preclinical and clinical studies that led to the proposed exploratory trial. Applicants must ensure that the data supporting the proposed trial meets the NIH scientific rigor guidelines. If the proposed trial plans to study the intervention(s) are based on preclinical mechanism studies, the application should summarize and reference the results from these studies.

Applicants must describe the rigor, robustness, and transparency of supporting data that are being used to justify the proposed trial and address any gaps identified. The proposed research plan should include a detailed description of the proposed UG3 and UH3 activities as described above. The application must describe the rationale for the trial design, population(s) and hypotheses being tested, and control groups.

Potential biases and/or challenges in the study design and protocol should be identified and addressed. The proposed study design should enable the rigorous assessment of outcomes focused on safety, tolerability, dosing, target engagement, or other appropriate measures. Participants within trial cohorts must be heterogeneous.

Timely access to trial data and associated biosamples to the broader research community is required. NIA urges investigators to follow the NIH's guidance for rigor and transparency in grant applications . This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully.

These recommended research practices include, where applicable, expressing clear rationale for the chosen primary/secondary endpoint(s), describing tools and parameters clearly, blinding, randomizing, ensuring adequate sample size, pre-specifying inclusion/exclusion criteria, appropriately handling missing data and outliers, implementing appropriate controls, preplanning analyses, and using appropriate quantitative techniques.

It is also strongly recommended to indicate clearly the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications. All trials, regardless of stage, must have clear go/no-go criteria for proceeding with a subsequent clinical trial(s).

The application should include a page listing the names and institutions of all providers of letters of support. If some trial costs are to be borne by sources other than NIH, include documentation of this support, signed by individuals who have the authority to make a commitment on behalf of the organization they represent, if it is available at the time of submission.

This may include, for instance, an agreement by a pharmaceutical company to donate study drug and placebo. 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. The Resource Sharing Plan must address which biosamples will be shared, where biosamples will be stored, and how approved parties will access these resources.

Biosamples must be available for sharing at the time of publication of the primary results or within 9 months of database lock, whichever comes first.

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. Applicants should describe the proposed methods and systems for data collection and quality control, and for ensuring data confidentiality and privacy, and the process for locking the final dataset and providing for data sharing.

Applicants should also describe the plans, if any, to use non-traditional data collection approaches (e.g., digital/mobile/sensor technologies and web-based systems) and why these are appropriate. Sharing of clinical trial data (participant level and summary level data, raw and processed) is expected at the time of publication of the primary results or within 9 months of database lock, whichever comes first.

The Data Management and Sharing Plan must address which data will be shared, where data will be stored, and how approved parties will access the data. NOT-OD-21-015 provides guidance regarding allowable costs associated with data management and sharing. The Data Management and Sharing Plan must also specify where the data will be stored.

Appropriate data repositories can be publicly supported or can be hosted by the home institution. Examples of NIA-supported public repositories include the Alzheimer's Clinical Trials Consortium (ACTC) and the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) . 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. Section 2 – Study Population Characteristics 2.

4 Inclusion of Women and Minorities Applicants must include a plan to enroll women and racial and ethnic minorities. The plan must also consider translation of