NIAMS Clinical Trial Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)

NIAMS Clinical Trial Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) is sponsored by National Institutes of Health (NIH). Supports implementation of clinical trials in musculoskeletal, rheumatic, and skin diseases.

PAR-25-141: NIAMS Clinical Trial Implementation Cooperative Agreement (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 National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Funding Opportunity Title NIAMS Clinical Trial Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement Notices of Special Interest associated with this funding opportunity 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 This Notice of Funding Opportunity (NOFO) solicits cooperative agreement (UG3/UH3) applications for implementation of investigator-initiated, single or multi-site, interventional clinical trials (all phases).

Investigators who have completed all necessary preparation (e.g., the trial design, protocol synopsis, data analysis plan, etc.) through other means may apply for a NIAMS UG3/UH3. The UG3 phase is designed to allow the investigators to prepare the final aspects needed to start the trial, (e.g., establishing the single IRB (sIRB), contracts and reliance agreements with sites, hiring of staff, etc.).

Transition to the UH3 phase to begin the trial is dependent upon completion of the UG3 milestones proposed by the investigator and approved by NIAMS. UG3 projects that meet their milestones will be administratively considered by NIAMS and prioritized for transition to the UH3 phase. NIAMS expects trials to be hypothesis-driven and have the potential for high clinical impact within the research mission of NIAMS.

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 Clinical research is a significant NIAMS investment aimed at answering critical questions about a particular disease or disease process.

It is essential to support clinical trial studies to test promising new interventions with the potential to improve health and impact clinical care. NIAMS is committed to improving health through effective approaches for arthritis and musculoskeletal and skin diseases and disorders. Improving health through the generation of high-quality data from well-designed and executed clinical trials is a high priority for NIAMS.

A clinical trial is defined by NIH as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes."

Clinical Observational studies (studies that do not involve an intervention) that aim to obtain information necessary for designing future clinical research studies; Exploratory Clinical Trial grants for studies with a relatively small number of subjects and short-term intervention; Phased Clinical Trial Implementation Cooperative Agreements for trials involving greater number of subjects, greater complexity, or higher risk.

Please see the NIAMS Clinical Research webpage for a listing of Investigator-Initiated clinical research opportunities. Large, more complex trials require substantial planning and preparation prior to beginning enrollment of human subjects, and investigators are expected to be ready to begin milestone completion for the start of the trial when the UG3 phase is awarded.

NIAMS strongly encourages prospective applicants to pay special attention to advanced preparation and planning in order to avoid delaying: (1) the conduct of these important studies, and (2) analysis of data and dissemination of results. All prior planning and preparation for the trial must be completed prior to applying for the phased UG3/UH3 award.

The 1-year UG3 phase is milestone driven and will allow an investigator to accomplish the final activities (e.g., establishing the single IRB (sIRB), contracts and reliance agreements with sites, hiring of staff, etc.) that are often necessary prior to implementing the clinical trial when transitioning to the UH3 phase.

Investigators who feel that they have already completed planning activities are strongly encouraged to consult with NIAMS staff in advance. Investigators considering applying to NIAMS for a clinical trial award should refer to the information found on the NIAMS Clinical Trial Policies, Guidelines, and Templates webpage .

This NOFO will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) mechanism consisting of a start-up phase of up to one year (UG3) and a full enrollment and clinical trial execution phase (UH3). There should be clear objectives for both a UG3 and a UH3 phases.

The UG3 phase will support the development of case report forms and other resources necessary to the performance of the trial; further development and finalization of study partnerships including signed contracts with performing clinical sites; single Institutional Review Board approval as well as NIAMS appointed Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), manual of operations, and clinical trial project management plans.

Applications are required to provide a clinical trial project management plan that delineates how the study will monitor and evaluate critical processes impacting feasibility of trial launch, conduct, and completion, coupled with on-time and on-budget performance milestones. All regulatory approvals should be obtained prior to the end of the UG3 award.

Procurement of the necessary drugs, matched placebos, or other resources should be planned for availability at the start of the UH3 award to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase.

Subject to NIAMS funding availability and scientific priorities, UH3 awards will be made after administrative review of a transition application with particular attention to the extent to which agreed upon milestones have been met.

The UG3 award supports the planning period and is not designed for the collection of preliminary data (neither clinical nor pre-clinical studies) about the efficacy or effectiveness of an intervention, or the collection of prospective data to support the rationale for a clinical trial.

Investigators will be asked to submit their UH3 phase transition application 2 months prior to transition, so the majority of UG3 phase milestones should be completed 2 months prior to transition to the UH3 phase. All milestones must be achieved prior to transition to the UH3 phase. The use of milestones is a key characteristic of this NOFO.

A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Plans must be guided by milestones that will be reached at the end of the UG3 phase. Milestones are to be objective and performance-based to achieve completion of the trial on time and on budget.

UG3 projects that have met milestones will be assessed administratively to determine eligibility for transition to the UH3 implementation phase. In situations when the milestones are not met, the transition will either be delayed until the milestones are completed and/or subsequent funding years may not be approved and may lead to phasing out the award.

This NOFO will support applications that include a series of milestones for completion of the clinical trial (UH3 phase) and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of NIAMS.

If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIAMS will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress. NIAMS staff will closely monitor progress at all stages, milestones, accrual, and safety.

UG3 Phase Milestones (as applicable) Development of data management system, and case report forms; Development of tools for data and quality management; Enrollment, retention, plans to minimize losses to follow-up, and acceptable attrition rates; Development of recruitment and retention strategies; Finalization of protocol, manual of procedures, and consent forms; Finalization of statistical analysis plan (including interim analyses, if appropriate); Initiation of contracts and training of clinical site personnel (NIAMS expects the initiation of all study sites to occur in the start-up stage; if a large number of sites is needed, a plan that describes how additional sites will be added after the initiation of the study should be included); Initiation of processes for including proposed international clinical sites, if applicable; Plans for site activation, execution of contracts and training of additional clinical sites, including any international sites, if applicable; Protocol approval from IRB and NIAMS appointed Data and Safety Monitoring Board.

UH3 Phase Milestones (as applicable) 1. Begin enrollment and follow-up of all subjects; 2. Register trial at www.

clinicaltrials. gov; 3. Register results with www.

clinicaltrials. gov as per FDAAA 801 requirements ; 4. Submit the primary publication within one year of completion of subject follow-up; 5.

Provide a complete, cleaned, and de-identified dataset and any supporting documentation (including but not limited to the study protocol, statistical analysis plan, and data dictionary) required for the analysis of the data within one year of the primary publication or within 18 months of the last study visit of the last subject, whichever occurs first. See the NIH guidelines on sharing research data .

The use of innovative and efficient study designs, such as adaptive dose-finding designs, designs incorporating plans for sample size recalculation, or futility designs, is encouraged.

Engaging People with Lived Experience and Other Collaborators People with lived experience (e.g., patients, patient advocates, caregivers, families, community leaders) have important insights that can improve meaningful outcomes, uptake of research findings, and health equity across the continuum of research from basic through implementation studies.

The perspectives of other relevant collaborators (e.g., health service providers, payors, public health agencies, community-based organizations, biotech, pharma) can further improve research impact. This announcement strongly encourages applicants to specify their plan for meaningful engagement of people with lived experience and other collaborators in the research process.

Meaningful engagement will vary with the focus of the research but should at minimum ensure that researchers are connecting with relevant collaborators and incorporating their perspectives throughout the conception, implementation, and dissemination of the research. Meaningful engagement should address what the researchers will learn and how the people with lived experience and/or collaborators will benefit from the partnership.

To promote health, as is relevant for the research proposed, it is recommended that at least two people with lived experience from populations who experience health disparities should be meaningfully engaged in these efforts. See this resource for more information in engaging people with lived experience: https://aspe. hhs.

gov/lived-experience . Submitting an Application for Clinical Trial Implementation Consultation with NIAMS staff prior to submitting the UG3/UH3 Clinical Trial Implementation Cooperative Agreement application is highly recommended. Applications that propose multi-site studies with multiple domestic sites are subject to the NIH sIRB policy as well as the sIRB requirement under the cooperative research provision ( 45 CFR 46.

114 ) . Information to guide investigators for preparation of clinical trial implementation can be obtained from the NIAMS Scientific/Research staff. NIAMS clinical research policy and guidance information as well as NIAMS templates for writing the manual of operating procedures and the data and safety monitoring plan are available at the NIAMS Clinical Study Tools and Templates website.

Examples of studies that might be supported by this NOFO include, but are not limited to: Clinical trials focusing on the prevention or treatment of a rheumatic, musculoskeletal, or skin disease or disorder; Clinical trials to investigate safety, efficacy, or effectiveness of novel therapeutic approaches for a rheumatic, musculoskeletal, or skin disease or disorder; Clinical trials testing methods to increase preventive health behaviors for a rheumatic, musculoskeletal, or skin disease or disorder.

Applications Not Responsive to this PAR: Studies involving animals are not responsive. Studies involving only Basic Experimental Studies Involving Humans (BESH) are not responsive. Applications that include intervention data collection in the UG3 phase are not responsive.

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 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. Applications budgets are limited to $250,000 direct costs for the UG3 phase, but are not limited for the UH3 phase. However, budgets need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The project period is limited to six years: up to one year for the first phase (UG3) and up to five years for the second phase (UH3). 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) 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 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. If parts of the costs of the trial are to be provided by sources other than NIAMS, these contributions must be presented in detail in the budget justification.

Third party support of the proposed research activity (if approved) will be incorporated as a specific term and condition in the Notice of Award. If the Third Party support ceases and the trial is no longer tenable without the Third Party support, a close-out plan may be requested.

Applicants are reminded that although Cost Share is not required; if these types of costs are included in the research application and peer reviewed, it is expected that these costs will not be covered by NIAMS. 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: Specific Aims: The goals of the trial and the expected outcome(s) should be concisely stated in the Specific Aims section. The specific objectives of the trial must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured.

There should be a clear explanation of the importance of various endpoints. Research Strategy: The Research Strategy should include the following information: Note: Discuss the following without duplicating information collected in the PHS Human Subjects and Clinical Trials Information Form . Describe the milestones to be completed during this 1-year time, including their rationale and justification.

These can include, for example, establishing the sIRB, contracts and reliance agreements with sites, production of case report and consent forms, and hiring of staff.

The research approach section should include A description of the supporting data (including strengths and weaknesses of the published literature), the study team's clinical trial experience, the experimental approach, and a milestone plan; A discussion of the overall strategy, methodology for the proposed research, and the types of analyses that will be conducted; A discussion of the significance of the problem being studied and how the study will test the hypothesis(es) proposed.

Address the need for this clinical trial to test either the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy; A discussion of the scientific rationale and how it supports the need to test the proposed hypothesis or intervention.

The scientific rationale should be well-supported by preliminary data, information in the literature or knowledge of biological mechanisms; A discussion of potential biases or challenges in the study and how they will be addressed; A description of how the study organizational structure and administration, including external committees, will contribute to the success of the project.

Discuss the impact of the organizational structure and administration on the scientific goals of the project; A description of any ethical issues surrounding the trial and the disease or condition under study; and If proposing an NIH-defined Phase III clinical trial, a review of the evidence to show whether or not clinically important sex and racial/ethnic differences in the intervention effect are to be expected.

The application must address plans for the valid analysis of group differences on the basis of sex, race, and ethnicity unless there is clear evidence that such differences are unlikely to be seen. Further, if the NIH-defined Phase III trial also meets the definition of an applicable clinical trial , additional requirements for reporting results of valid analyses in clinicaltrials. gov must be followed.

See NOT-OD-18-014 . 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.

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. Section 5 - Other Clinical Trial-Related Attachments 5.

1 Other Clinical Trial-Related Attachments The application must contain the following information, according to the instructions below, to provide evidence that the investigator(s) has planned a feasible clinical trial. The information provided here supports the Research Strategy and should not duplicate it. The following documents must be uploaded as separate .

pdf files with the names indicated below. Attachments may be appended as needed for each study record (e.g., "Clinical Monitoring Plan1. pdf" for study record 1, etc.).

1. Clinical Monitoring Plan: The Clinical Monitoring Plan is a required attachment and must use the filename "Clinical Monitoring Plan. pdf."

Applications lacking this attachment will be considered incomplete and will not be reviewed.

The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s): Describe the persons/entity responsible for conducting the clinical monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, independent study monitor from the Clinical Coordinating Center); Describe the frequency of planned monitoring activities (e.g., study initiation, interim visits, study close out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center), and what data will be reviewed; Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions.

Include methods to monitor study data collected and systems to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities, such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens.

Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements; Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, data and safety monitoring body, FDA if applicable, OHRP, institutional officials, and NIH; Describe methods and systems to ensure confidentiality and subject privacy; Describe process for locking the final trial datasets.

2. Study Timeline: Applicants should provide detailed project performance objectives and corresponding timeline. The proposed milestones must include achievable goals for each stage of the project as follows: 1.

Development of data management system and case report forms; 2. Development of tools for data and quality management; 3. Enrollment, retention, plans to minimize losses to follow-up, and acceptable attrition rates; 4.

Development of recruitment and retention strategies; 5. Finalization of protocol, manual of procedures, and consent forms; 6. Finalization of planned analyses (including interim analyses, if appropriate); 7.

8. Protocol approval from IRB and DSMB; 9. Initiation of contracts and training of clinical site personnel (NIAMS expects the initiation of all study sites to occur in the start-up stage; if a large number of sites is needed, a plan that describes how additional sites will be added after the initiation of the study should be included); 10.

Initiation of processes for including proposed international clinical sites, if applicable; 11. Plans for site activation, execution of contracts and training of additional clinical sites, including any international sites, if applicable; 12. Completion of start-up activities (finalization of protocol, contracting of sites, registration in ClinicalTrials.

gov, completion of any final regulatory approvals, etc.) 1. Earliest possible enrollment date; 2. Enrollment of 25%, 50%, 75% and 100% of the targeted