Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

The NIAMS is committed to identifying effective approaches to address the burden of 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 the 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 intervention (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." See more at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html. It is highly recommended that applicants consult with NIAMS Scientific/Research staff to determine if the U34 is the appropriate mechanism.

The NIAMS has redesigned its clinical trials program in order to support the spectrum of such studies with funding mechanisms tailored to different levels of complexity. For clinical trials involving a relatively small number of subjects and short-term interventions, applications should be submitted to PAR-14-192, Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R21). Clinical observational studies (studies that do not involve an intervention) that aim to obtain information necessary for designing future clinical trials and feed into the other components of the NIAMS overall program should be submitted to PAR-15-115, Clinical Observational (CO) Studies in Musculoskeletal, Rheumatic, and Skin Diseases (R01)." For trials involving greater numbers of subjects or of greater complexity or risk, investigators should apply for funding through the NIAMS Clinical Trial Implementation Cooperative Agreement (U01) for a single- or multi-site trial. These larger and more complex trials require substantial planning and preparation prior to opening for recruitment, and investigators are expected to be able to begin the trial without further planning activities when the U01 is awarded. In order to accomplish necessary planning with NIAMS support, investigators may apply for a NIAMS Clinical Trial Planning Grant (U34) prior to submitting an application for the U01 to implement the trial. The planning grant will allow an investigator to accomplish the planning activities (preparation of the manual of operating procedures, FDA approvals, etc.) that are often necessary for actually implementing a clinical trial. Investigators who have already completed planning activities either by a previously awarded NIAMS U34, R34, or other means may also submit a U01 implementation application, but are strongly encouraged to consult with NIAMS staff in advance. Investigators considering applying to the NIAMS for a clinical trial award should refer to the NIAMS Clinical Trials Policy web site.

Investigators are strongly encouraged to contact the Scientific/Research contact listed in Section VII. Agency Contacts prior to submitting applications for a U34 clinical trial planning application or a U01 clinical trial implementation application. This FOA, NIAMS Clinical Trial Planning Cooperative Agreement (U34), addresses the planning phase; a companion FOA addressing the second part of the process for implementing a Clinical Trial Implementation Cooperative Agreement (U01) is also available PAR-15-165.

Background

Clinical research is a significant NIAMS investment aimed at answering critical questions about a particular disease or disease process. It is essential to support studies to test promising new interventions with the potential to improve health practices and clinical care. Special attention must be paid to enabling these important studies to get through the administrative processes at a reasonable pace so that the conduct of the study, analysis of data, and dissemination of results are not delayed.

The NIAMS has determined that investigator-initiated, interventional clinical trials requesting NIAMS

support should undergo a rigorous planning, design, and documentation phase before a decision is made to implement a study with a substantial fiscal and human resource investment. The implementation of a clinical trial requires extensive administrative planning (e.g., protocol finalization, manual of operations development, establishing collaborations and estimating recruitment potential) before participant recruitment can occur. The NIAMS is offering this two-part process that separates planning from subject recruitment and study implementation to provide adequate support and facilitate the timely implementation of the studies important to the mission of the Institute. In addition, use of the cooperative agreement mechanism will allow NIAMS programmatic input during the early planning stages and throughout the conduct of the actual clinical trial.

The U34 planning grants will give investigators the time and funds necessary to complete detailed clinical trial planning to meet NIAMS and NIH standards and regulatory requirements. A structured planning process will allow studies to determine the optimal design strategy and to complete the administrative activities as expeditiously as possible so that the implementation phase (U01) can start and finish the required activities within a five-year grant period.

Part 1: Clinical Trial Planning Phase (U34)

The U34 planning grant is expected to precede the submission of a clinical trial cooperative agreement (U01) application, although this is not a requirement. The U34 will provide support to complete the administrative and planning activities that are required prior to subject recruitment. These activities may include, but are not limited to: establishing the research team, identifying collaborators and clinical sites, developing the protocol and clinical investigators brochure, writing of the manual of operating procedures (MOP), establishing a data and safety monitoring plan, developing tools for data collection and data management, and initiating the IRB approval process (the NIAMS strongly encourages the use of a central IRB) and submitting an application to the Food and Drug Administration (FDA) for an Investigational New Drug (IND) application, IND exemption, or Investigational Device Exemption (IDE), etc. Guidelines to help investigators develop a MOP and data and safety monitoring plan can be found on the NIAMS clinical research page.

The NIAMS U34 is intended to support necessary administrative study activities before recruitment of subjects into the future clinical trial begins. The U34 cannot be used to recruit subjects. In addition, it cannot be used to collect data on research participants unless those data are only to define recruitment strategies on a potential pool of interested and eligible subjects (e.g., through conducting model recruitment using focus groups, questionnaires, etc.).

The study design and protocol for the proposed trial should be presented in the U34 application in sufficient detail so that a review group can judge the feasibility of the proposed approach and the potential significance of the trial. In instances where basic protocol development can best be completed with U34 funding, the application should indicate why this is the case and indicate how the funding will be used to complete the design of the study.

The U34 is not designed for the conduct of pilot studies to support the rationale for a clinical trial or the collection of preliminary data. Additionally, enrollment into the proposed future clinical trial cannot begin under the NIAMS U34. Please refer to PAR-14-192 "Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R21)" or PAR-15-115 "Clinical Observational (CO) Studies in Musculoskeletal, Rheumatic, and Skin Diseases (R01)" for clinical trial/observational study funding opportunities supported by the NIAMS.

Prospective applicants should note that funding of a U34 planning grant does not guarantee or imply funding for a subsequent application for a U01 clinical trial. The U34 cooperative agreement will provide up to two years of support; although it is expected most will only need one year of support.

Part 2: Clinical Trial Implementation Phase (U01)

The product of an awarded U34 planning grant that has met its milestones, as submitted in the application and as approved by the PD/PI and the NIH Program Official, will be an application (U01) to conduct the clinical trial. It is expected that a U34 planning grant will lead to the timely submission of an application for support of the full-scale study which incorporates the elements developed under the planning grant. If the planning phase is not successful, an investigator may decide not to proceed to an application for the U01 clinical trial.

It is expected that all investigators who are considering submitting an application for a U01 Clinical Trial Implementation Cooperative Agreement will begin by submitting a U34 application. However, an applicant may not need a U34 planning grant if all of the administrative activities relating to the start-up of the study (e.g., the U34 milestones) are complete. If a clinical trial is ready for implementation without a planning phase, and readiness is adequately supported by documentation, a U01 application may be submitted without a preceding U34. The investigators must be ready to implement the proposed trial by the time the U01 is to be awarded. Note that for U01 applications which have direct costs of $500,000 or greater in any year, prior approval for submission must be obtained from the NIAMS per the NIH large grant policy. Please refer to (NIAMS website) for details on what should be included in the request to NIAMS.

All U01 clinical trial cooperative agreement applications will be peer-reviewed, and the NIAMS will consider the results of the peer-review process when deciding whether to support the study.

Scope of the U34 Planning Grant

The U34 planning grant process is designed to permit early peer review of the rationale for the proposed clinical trial and to provide support for the applicant to establish the research team, develop tools for data management and oversight of the research, define recruitment strategies, develop and finalize the clinical protocol and all essential elements of the study required for the clinical trial including all the appropriate documents.

The activities proposed in the U34 planning grant will depend on the type and complexity of the study (e.g., drug trial, surgical, or behavioral intervention). Activities supported by the U34 planning grant include, but are not limited to, the following examples:

• Assess potential design strategies to capture the optimal intervention, dose, and target population
• Develop a final study protocol
• Develop a manual of operating procedures (MOP) including details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed
• Develop an investigator’s brochure or equivalent
• Develop consent form(s) and, if applicable, assent form(s)
• Develop a recruitment plan including the inclusion of women and minorities, and children
• Conduct model recruitment as described above
• Obtain required Office of Human Research Protections (OHRP) assurances if not already in place
• Satisfy all regulatory elements of the FDA
• Initiate the IRB approval process; the NIAMS strongly encourages the use of a central IRB
• Develop a complete set of suitable documents for submission to the appropriate regulatory authorities (i.e., IND or IND exemption, or IDE application)
• Develop a safety monitoring plan to address how risk to subjects in the clinical trial will be minimized and the process for collecting and reporting of adverse events to the appropriate regulatory bodies
• Develop a detailed project timeline and budget for conduct and completion of the clinical trial including funding for orderly close-out of clinical sites and preparation of a final study report
• Identify collaborators and clinical site(s), which may include negotiating sub-contracts
• Develop training materials and training/certification plans for study staff who will carry out the study
• Negotiate agreements with industry, as needed, to provide drugs, devices, or other resources

In the event of an award, the NIAMS and the PD/PI will agree on a list of milestones to be completed during the U34 project period. They are derived from the specific activities that need to be completed before an implementation trial can be initiated. The submission of the application for the U01 may be one of the milestones and may precede the end of the U34. The milestones will be incorporated into the notice of grant award (NoA).

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

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)

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

Other

• Independent School Districts
• ublic 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 Institutions) 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 SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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. 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 NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Anna Nicholson, MSHS,
Telephone: 301-594-2463
Fax: 301-402-7478
Email: nicholsona@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: The following items should be included in the Research Strategy:

Rationale/Significance - Provide the rationale for the proposed clinical trial, documenting the significance and need to perform the study, detailing potential risks and benefits. Also provide justification of the need for the planning activities prior to conducting the trial. Describe the potential of the clinical trial to affect health care, policy or practice. Include sufficient background information to enable reviewers to assess appropriateness of design, selection of experimental and comparator arms, and appropriateness of proposed study population.

Study Design- Sufficient details of the clinical trial (such as overall study design, primary objective, inclusion and exclusion criteria, proposed study population, proposed study agent(s), sample size, study end points and duration of recruitment and follow-up) should be included to permit assessment of the scientific importance and feasibility of the trial. In instances where basic protocol development can only be completed with U34 funding, the application should indicate why this is the case and indicate how the support will be used to complete the design of the study. The application must describe and address the availability of the requisite patient/subject population and plans for recruitment outreach and follow-up. In addition, plans for addressing issues and challenges regarding adherence to the proposed intervention protocol should be included.

Planning Activities - Specify how the planning period will be used. The application should include the rationale for the planning period, descriptions of the activities to be carried out, and a clear explanation as to how each aim and activity will be completed during the planning period. Enough information should be provided to allow reviewers to evaluate how the clinical trial documents will be developed. Clear milestones and a timeline for completion of each should be provided.

Research Team - The application must include a description of the leadership and proposed organization of the clinical trial, including proposed clinical sites (letters of commitment are not required at this stage). This includes the ability of the PD/PI to bring together the necessary study network. Describe the mechanism for identification and selection of additional collaborators.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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 SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Prior consultation with the NIAMS is strongly encouraged for submission of the NIAMS Clinical Trial Planning (U34) Grant application, including new and resubmission applications. NIAMS staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and whether it is appropriate to conduct it as an investigator-initiated clinical trial, but will not evaluate the technical and scientific merit of the proposed trial. Technical and scientific merit will be determined during peer review. In the presubmission consultation phase, if the proposed trial does not meet the goals and mission of the NIAMS, applicants will be so informed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Will the future trial lead to a better understanding of mechanisms of health and/or disease, change clinical practice, community behaviors or health care policy? Is there a clear rationale for the proposed hypothesis or intervention in the planned trial? Is the premise for the proposed intervention well supported by preliminary data, information in the literature or knowledge of biological mechanisms? Are the proposed planning activities well justified? Do the specific aims of the planning grant identify areas that are needed for the future clinical trial? Do the proposed planning activities address all major barriers to the future clinical trial and prepare for timely recruitment of subjects and implementation of the future clinical trial? Has a clear rationale been presented to justify the development of each study document? For projects where basic trial design is not yet complete, is justification provided as to why funds are needed to complete its development? What is the potential of the proposed project to effectively address all key issues that currently prohibit completion of the trial design?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Are the investigators involved in the planning period and are their roles in the future clinical trial clearly specified? Are the expertise and ability of the investigator (and the clinical trial team) adequate to develop, organize, manage, and execute the proposed trial?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: Does the application take on an important clinical question or apply rigorous methodology to an outstanding clinical question?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Specific to this FOA: Are the aims and activities of the planning period clearly and adequately described, such as the specification of the study documents, data and safety monitoring plans, subject recruitment plans, identification of collaborators and sites, staff training, and protocol/study development? Is there an appropriate and feasible timeline for these activities and are clear milestones presented? For projects where basic trial design is not yet complete, is there an adequate plan to do so? Are appropriate milestones provided for the design, implementation and evaluation of the planning phase? How feasible is the plan and how appropriate is the plan for the development and preparation of the subsequent trial?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: Is there evidence for adequate resources, such as a data coordinating center or study personnel that would allow for adequate trial performance, including safety monitoring, compliance with human subjects protection, and monitoring of data integrity?

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.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Not Applicable

Not Applicable

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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAMS, in accordance with NIH peer review policy and procedures, 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:

• 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.
• Will receive a written critique.

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 FOA. Following initial peer review, recommended applications will receive a second level of review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC). 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.

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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 (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 awardees 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 award 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

All aspects of the study, including any modification of study design, conduct of the study quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators, including setting up and convening any external advisory or steering committees. The awardee agrees to accept close coordination, cooperation, and participation of NIAMS staff in those aspects of scientific and technical management of the study as stated in these terms and conditions:

• Carrying out the activities essential to the planning of the clinical trial.
• Research design and protocol development, including definition of objectives and approaches, planning, implementation, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.
• Establishing a Steering Committee to coordinate and manage the project. Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically, according to established timeline.
• Developing and adhering to the study milestones and timeline and submitting interim progress reports, when requested, to the NIAMS Program Director.
• Attendance and participation in Steering Committee activities and workshops, if proposed.
• Awardees who do not accomplish the negotiated milestones shall submit a milestone report which will include a discussion of why the milestones were not met in the agreed upon timeframe, and propose a corrective action plan. The corrective action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NIAMS staff. The plan shall be provided to NIAMS staff no later than 2 months following the missed milestone.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

The NIAMS Project Collaborator will:

• Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAMS staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
• Attend Steering Committee meetings or other external advisory committee meetings or workshops, as appropriate.
• Review and comment on critical stages of the planning grant development and assess the overall study progress based on the established milestones.
• Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration;
• Retain the option of recommending modification or additional endeavors to planning projects within the constraints of the approved budget to meet the goals of the planning phase.
• Implement adjustments to the study if appropriate performance milestones are not achieved.
• In addition, an agency program official or IC program director may be responsible for the normal scientific and programmatic stewardship of the award and may be named in the award notice.

Areas of Joint Responsibility include:

• Participation in Steering Committee meetings and other external meetings or workshops organized by the awardee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees 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 progress report, 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Shahnaz Khan, MPH
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-2463
Email: Khanshah@mail.nih.gov

Anna Nicholson, MSHS
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-2463
Email: nicholsona@mail.nih.gov

Charles Washabaugh, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-496-9568
Email: washabac@mail.nih.gov

Mark Langer
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-451-8216
Email: langerM@mail.nih.gov

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 45 CFR Part 75.