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 (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of PAR-15-165

Related Notices
  • May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062.
Funding Opportunity Announcement (FOA) Number

PAR-16-447

Companion Funding Opportunity

PAR-16-446, R34 Planning Grant

PAR-15-115, R01 Research Project Grant
PAR-14-192, R21 Exploratory/Developmental Research Grant
PAR-17-293, R21 Exploratory/Developmental Grants

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.846

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites cooperative agreement (U01) applications for implementation of investigator-initiated interventional clinical trials (all phases).  Applications for clinical trials submitted to the NIAMS are normally expected to go through a two-part process, which begins with an R34 planning phase (Part 1) followed by an application for the U01 (Part 2).  Investigators who have completed all necessary pre-trial planning and preparation through other means may apply for a NIAMS U01 without having applied for a R34.  The NIAMS expects such trials to be hypothesis driven, milestone-defined, and have the potential for high impact within the research mission of the NIAMS.

Key Dates

 

Posted Date

September 23, 2016

Open Date (Earliest Submission Date)

February 1, 2017  

Letter of Intent Due Date(s)

30 days before application due date  

Application Due Date(s)

March 1, 2017; July 3, 2017; November 1, 2017; March 2, 2018; July 2, 2018; November 1, 2018; March 1, 2019; July 1, 2019;November 1, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July 2017, October/November 2017, February/March 2018, June/July 2018, October/November 2018, February/March, 2019, June/July 2019, October/November 2019, February, March 2020                    

Advisory Council Review

October 2017, January 2018, May 2018, October 2018, January 2019, May 2019, October 2019, January 2020, May 2020  

Earliest Start Date

December 2017, April 2018, July 2018, December 2018, April 2019, July 2019, December 2019, April 2020, July 2020 

Expiration Date

November 2, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research Instructions for 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.


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

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

  3. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

Table of Contents

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


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
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 clinical studies to test promising new interventions with the potential to improve health practices and clinical care. The NIAMS is committed to identifying effective approaches to address 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 interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

The NIAMS has designed its clinical trials program to support a broad spectrum of research and trial designs by offering funding opportunities that are tailored to different levels.

  • Applications for 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)."
  • Applications for clinical trials involving a relatively small number of subjects and short-term interventions should be submitted to PAR-14-192, “Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R21).”
  • For trials involving greater numbers of subjects, greater complexity or higher risk, investigators should apply for funding through this NIAMS Clinical Trial Implementation Cooperative Agreement (U01) for a single- or multi-site trial. It is worth noting that these larger and more complex trials require substantial planning and preparation prior to beginning enrollment of human subjects, and investigators are expected to be ready to begin the trial without further planning activities when the U01 is awarded. NIAMS strongly encourages prospective applicants to pay special attention to advance preparation and planning in order to avoid delaying: (1) the conduct of these important studies, and (2) analysis of data and dissemination of results.

In order to accomplish necessary planning with NIAMS support, investigators may apply for a NIAMS Clinical Trial Planning Grant (R34) prior to submitting an application for the U01 to implement the trial.  The planning grant will allow an investigator to accomplish the planning activities (manual of operating procedures, FDA approvals, etc.) that are often necessary prior to 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. Information about NIAMS Policies, Guidelines and Sample Templates for Clinical Trials is located at http://www.niams.nih.gov/Funding/Clinical_Research/NIAMS_guidelines.asp

Submitting an Application for Clinical Trial Implementation

Once appropriate planning milestones have been completed, either through an R34 or some other means, investigators may apply for the U01 Clinical Trial Implementation Cooperative Agreement.

Each U01 clinical trial implementation application must include a Clinical Protocol Synopsis, a Clinical and Data Monitoring Plan, an Intervention Document, a Statistical Analysis Plan, and a Milestone Plan.   Applications and associated documents should meet all applicable NIAMS, NIH, Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) policy requirements. Information about Institutional Review Board and Independent Ethics Committee (IRB/IEC) registration and assurances can be found at http://www.hhs.gov/ohrp.  The NIAMS strongly encourages the use of a central IRB for studies proposing to involve multiple domestic sites. Applications received after May 2017 that propose multi-site studies with multiple domestic sites, are subject to the new NIH Single IRB policy as indicated in NOT-OD-16-094

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 following website: http://www.niams.nih.gov/Funding/Clinical_Research/NIAMS_guidelines.asp.

Examples of studies that might be supported by this FOA 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 one or more of these conditions;
  • Clinical trials testing methods to increase preventive health behaviors for one or more of these
  • conditions.

Each NIAMS U01 Clinical Trial Implementation Cooperative Agreement award will support the implementation of a single clinical trial. 

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support 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 FOA.

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

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.

Award Budget

Application budgets are not limited but should reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The project period may not exceed five years.    

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.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

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

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.

Required Registrations

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.

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 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.

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. 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 Instructions for 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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Shahnaz Khan, MPH
Telephone: 301-451-9893
Fax: 301-480-4543
Email: Khanshah@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other 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.

1. Clinical Protocol Synopsis: The complete Clinical Protocol Synopsis is a required attachment.  It should be no more than 10 pages in length, and the attachment must use the filename "Clinical Protocol Synopsis.pdf."  Applications that lack a Clinical Protocol Synopsis or any of the elements listed below will be considered incomplete and will not be reviewed.  Applications that exceed the 10-page limit for the Clinical Protocol Synopsis will not be reviewed.

The Clinical Protocol Synopsis is expected to include the following information that supports the Clinical Trial Protocol Overview section in the Research Strategy:

  • Brief and/or Official Protocol Title
  • Intervention to be tested: A description of the intervention to be tested, and a brief description of the protocol to be followed in each arm of the trial.
  • Intervention / dosage and frequency: If applicable provide a description of the dose frequency and type of administration of the intervention(s).
  • Primary and important secondary endpoints: Specify the endpoints for the primary and, if applicable, important secondary endpoints.
  • Study Population: A description of the study population, including the sample size, gender, age, demographic group, required health status, and geographic location.
  • Inclusion/Exclusion Criteria
  • Recruitment plans: A discussion of the availability of potential participants for the proposed study and the ability of participating sites to recruit and retain the proposed target number of participants.
  • Retention plans: Approaches to be used for retention, cooperation and follow-up of those enrolled and to address any anticipated changes in the composition of the study population over the course of the trial.
  • Group Assignment: Describe methods used to assign participants to study groups (treatment arms) and randomization.
  • Subject Participation Duration: Time it will take for an individual participant to complete all study visits. When possible provide a brief snapshot of the protocol’s schedule of events capturing time points and planned activity at study visits. For example:
  • ·    Week 1 Screening/Baseline Visit (4 hours) - eligibility criteria, obtain informed consent, screening assessment(s), labs, etc.;
  • ·    Week 2,4,6,8, Study Visit(s) (3 hours) – intervention(s), assessment(s), labs, scan(s) etc.;
  • ·    Week 12 and 18 Follow-up visits (3 hours) - assessment(s), labs, scan(s) etc.;
  • ·    Week 24 End of study visit (2 hours) - assessment(s), labs, scan(s) etc.
  • Study Duration: Estimated time (in months) from when the study opens to enrollment until: (a) completion of data collection; and (b) final data analyses.
  • Availability of Investigational Product (IP) and IND/IDE status: If applicable, provide a summary of the availability of IP and support for acquisition and administration. Please indicate the IND/IDE status of the IP, if applicable, and whether or not the investigators have had any interactions with the Food and Drug Administration (FDA). If the agent currently has an IND/IDE number, provide that information. Note that the NIH IC may request consultation with the FDA and the IND/IDE sponsor about the proposed clinical trial after peer review and prior to award.
  • FDA info on early feasibility studies: If applicable, provide FDA info available on early feasibility studies.

2. Clinical and Data Monitoring Plan:  The Clinical and Data Monitoring Plan is a required attachment and must use the filename "Clinical and Data Monitoring Plan.pdf." Applications lacking this attachment will be considered incomplete and will not be reviewed. Each Clinical and Data Monitoring Plan includes 2 parts: (A) The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical monitoring activities, and (B) the Data Monitoring Plan for the quality controls proposed through data monitoring activities.

The NIH requirements for monitoring clinical trials as described below are in addition to the application's Data and Safety Monitoring Plan (DSMP) attachment on the PHS 398 Research Plan form which describes how patient safety in the trial will be monitored, and the regulatory requirement in 45 CFR 46 for on-going review and approval of all non-exempt human subjects research by the IRB of record.

Part A: 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 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 intervention and system 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, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Monitoring Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

  • Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance.
  • Describe methods and systems to ensure data confidentiality and subject privacy.
  • Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

3. Intervention Documents: The Intervention Documents attachment is required and must use the filename "Intervention Documents.pdf." Applications that lack an Intervention Documents attachment will be considered incomplete and will not be reviewed.  The Intervention Documents should include one of the following documents according to the type of intervention(s) to be used in the proposed clinical trial:

  • Investigator's Brochure and Description: (provide for trials in which the interventions are other than behavioral or social). A compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects.
  • Intervention Monitoring Manual(s): (provide for trials in which the interventions are behavioral or social). A document that describes in detail the content and delivery of the intervention, the intervention manual should describe how to conduct the intervention, how to train the interventionists, how to monitor fidelity in delivering the intervention, and the rationale for the specified intervention. 

4. Statistical Analysis Plan: The Statistical Analysis Plan is a required attachment and must use the filename "Statistical Analysis Plan.pdf."  Applications lacking a Statistical Analysis Plan will be considered incomplete and will not be reviewed.  The Statistical Analysis Plan should provide the detailed analysis necessary for the proposed clinical trial and should include:

  • A concise description of the overall strategy, methodology, and analyses to be used to accomplish the goals and specific aims of the trial;
  • A description of the proposed study design and rationale for its selection with respect to the translation of the clinical question into a statistical hypothesis;
  • A description of the statistical methods that are appropriate for the study design, including sample size, duration of the trial; power calculations and the underlying assumptions (and data) used to link these calculations to the endpoints and to the hypothesis(es) being tested should also be described. Provide justification for the primary and secondary outcome variable(s) and data to be collected, and the relevance to the clinical and statistical hypothesis being tested;
  • A description of the methods for randomization, masking, and selection of control groups, and specific analytic techniques and plans for handling dropouts, missed visits, and losses to follow-up.

5. Milestone Plan: A Milestone Plan is a required attachment and must use the filename "Milestone Plan.pdf." Applications that lack the Milestone Plan will be considered incomplete and will not be reviewed.

The Milestone Plan provides detailed project performance and timeline objectives and must include a timeline for the following general milestones, as applicable:

  • Finalization of clinical protocol (with program agreement, if applicable);
  • Registration of clinical trial in ClinicalTrials.gov;
  • Completion of regulatory approvals;
  • Enrollment of the first subject;
  • Enrollment and randomization, if applicable of 25%, 50%, 75% and 100% of the projected study population, including women, minorities and children (as appropriate);
  • Completion of data collection time period;
  • Completion of primary endpoint and secondary endpoint data analyses;
  • Completion of final study report;
  • Reporting of results in ClinicalTrials.gov;
  • Other protocol-specific performance milestones and timeline; these milestones will be negotiated at the time of the award, if appropriate.

There is no page limit for the Milestone Plan, but applicants should not attempt to circumvent application page limits by including irrelevant information that belongs in another section of the application.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

All instructions in the SF424 (R&R) 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:

Clinical Trial Protocol Overview: For the proposed clinical trial, this brief section should provide an overview that includes:

  • A summary of the study protocol’s objectives describing the scientific rationale and clinical need for the trial, the condition or focus of study, the trial’s potential impact, an assessment of the previous preclinical and clinical studies and their quality.
  • A description of the study design which should include the following information:
  • Primary Purpose (e.g., Treatment, Prevention, Diagnostic, etc.);
  • Type of Intervention (e.g., Drug, Biologic, Device, Behavioral);
  • Study Phase (e.g., Pilot, Phase 1, 1/2, 2, 2/3, 3, or 4);
  • Interventional Model (e.g., single-group, parallel, cross-over, factorial);
  • Masking (e.g., open, single blind, double blind);
  • Allocation (e.g., single-arm, randomized, non-randomized).

Applicants should not duplicate information about the protocol that was requested in the attachment called "Clinical Trial Synopsis." 

Other information to be provided in the Research Strategy:

  • A discussion of the significance of the problem being studied and how the trial 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 premise for the trial and how it supports the need to test the proposed hypothesis or intervention; the premise 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 protocol and how they will be addressed;
  • A description of the study organizational structure and administration, including, but not limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any subcontractors or service providers for personnel or facilities, and the impact of the organizational structure on the scientific goals of the project; and
  • If a Phase III trial, describe how the potential findings are likely to be generalizable. Describe any ethical issues surrounding the trial and the disease/condition under study. Provide evidence showing whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected (see Inclusion of Women and Minorities in Clinical Research).
  • This should not duplicate information already covered in other attachment 2, “Clinical and Data Monitoring Plan.”

Applicants planning Phase 2 or Phase 3 clinical trials that require investigational new drug (IND) or investigational device exemption (IDE) applications should provide elements that are consistent with the requirements of the Food and Drug Administration (FDA) IND or IDE. A proposed protocol template for such studies can be found here: http://osp.od.nih.gov/sites/default/files/Protocol_Template_05Feb2016_508.pdf

Data and Safety Monitoring Plan Do not duplicate information already covered in Other Attachment 2, “Clinical and Data Monitoring Plan.” Note that if an application is awarded, the NIAMS will organize an independent Data Safety and Monitoring Board or appoint a Safety Officer based on the risk and complexity of the trial. 

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, with the following modifications:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Applications should describe plans to ensure that the data and biospecimens are collected in a manner that will promote appropriate data sharing and integration into larger databases (e.g., use of common data elements, see http://cde.nih.gov/), consistent with achieving the goals of this program. Applications should address strategies to ensure that data are collected in a manner that could allow other researchers to analyze the data, including conducting meta-analyses, and provisions to support rapid sharing of trial data, as appropriate

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.

PHS Inclusion Enrollment Report

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 10 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.  For information about what to include in the Letter of Request (LOR), applicants are directed to the NIAMS website at   http://www.niams.nih.gov/Funding/Clinical_Research/clinical_letter_request.asp and strongly encouraged to contact the appropriate Program Officer prior to submitting the LOR.

Prior Consultation

Prior consultation with the NIAMS at least 10 weeks prior to the application due date is strongly encouraged for submission of the NIAMS U01 Clinical Trial Implementation 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 pre-submission consultation phase, if the proposed trial does not meet the goals and mission of the NIAMS, applicants will be so informed.  If the NIAMS ascertains that substantial additional planning may be necessary, the investigator(s) will be encouraged to submit an application for the Clinical Trial Planning Grant (R34) FOA, and delay the submission of the U01.

 
Post Submission Materials

Applicants are required to follow our Post Submission Application Materials policy.

Section V. Application Review Information
1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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.

Significance

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:

Is the premise for the proposed intervention well supported by preliminary data, information in the literature or knowledge of biological mechanisms? Are the potential findings likely to be generalizable?  Are there ethical issues surrounding the trial and the disease/condition under study?  Does the status of evidence show whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected; and if so, are these differences to be addressed (see Inclusion of Women and Minorities in Clinical Research)? Is this trial likely to change clinical practice?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have clinical trial-specific expertise and experience; the ability to organize, manage and implement the proposed clinical trial and meet study milestones and timelines? Do they have appropriate capacity in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate?   

Innovation

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 study design/research strategy include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance the field, clinical practice or practice guidelines?    

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in human subjects? 

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?

Specific to this FOA:

If potential threats to the data integrity are known about the proposed research, will these threats affect the feasibility of the proposed research?

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the clinical and statistical hypothesis being tested? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified? Is there a plan to complete data analysis within the proposed period of the award?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure data collection? Is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed?   

Environment

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?   

Additional Review Criteria

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.

Clinical Data Monitoring Plan

Are the procedures for clinical data monitoring and quality control of data adequate? Are standardized systems and controls in place for data monitoring to ensure data integrity and to assess the effect of the intervention?

Study Timeline and Milestones

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are appropriate, evaluative milestones clearly defined for the aims associated? Are the milestones feasible and quantifiable with regard to specific aims and timeline? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Organizational Plan

Is the proposed organizational structure for the single-site or multi-site trial appropriate? What impact does the organizational structure have on the scientific goals of the project? Is there evidence of the ability of the individual center(s) to (1) enroll the proposed numbers, (2) adhere to the protocol, (3) collect and transmit data in an accurate and timely fashion, and (4) operate within the proposed organizational structure?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children 

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

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.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

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 Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 . 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.
3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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:

  • Meeting NIAMS policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. The full NIAMS policy and guidelines are available at: http://www.niams.nih.gov/Funding/Clinical_Research/NIAMS_guidelines.asp;
  • Upon implementation of the protocol, each site, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, data collection, and quality control;
  • Managing involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIAMS;
  • Making all study materials and procedure manuals available in the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIAMS/NIH;
  • 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 recruitment action plan, if appropriate.  The corrective recruitment 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; and
  • 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.

NIH staff has 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, including the Project Collaborator, 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.  In addition, the NIAMS Project Collaborator may:

  • 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;
  • Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from the NIAMS grantees and contractors, advising in management and technical performance, or participating in the preparation of publications;
  • Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting;
  • Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the safety monitoring meetings (or DSMB) and related external advisory committee meetings or steering committee meetings;
  • Monitor progress of study milestones. At each scheduled interim review, compare actual enrollment to the benchmarks and criteria identified in the application and negotiated prior to award;
  • Studies in which recruitment milestones are not met as per criteria established pre-award, or for which regulatory approval has not been met within one year, and are deemed unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress following review and consideration by NIAMS staff (including the Project Collaborator):
  • If a study is finally determined to lack feasibility and will no longer accrue subjects, awardees are required to submit a close-out plan to NIAMS staff (including the Project Collaborator) within three months of a decision either by NIAMS Project Collaborator or the grantee that an awarded study is no longer feasible.  The plan must be approved and signed by the Institutional Official and the PI/PD(s) listed on the award prior to submission;
  • The NIAMS may terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which the NIAMS does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.

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:

Data Safety and Monitoring Board: An independent Data and Safety Monitoring Board will be established by the NIAMS. The Data and Safety Monitoring Board will review interim results periodically as established in the data and safety monitoring plan and report to the NIAMS Project Collaborator. The NIAMS Project Collaborator will report in writing to the PD/PIs on the recommendations of the DSMB and the NIAMS concurrence/non-concurrence of the DSMB recommendations. The PD/PIs will assume responsibility for reporting of the DSMB and the NIAMS recommendations to their respective Institutional Review Boards.

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 PD/PIs, 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.

3. Reporting

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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 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: 301-945-7573

Scientific/Research Contact(s)

Shahnaz Khan, MPH
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-451-9893
Email: Khanshah@mail.nih.gov

Peer Review Contact(s)

Kathy Salaita, ScD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: salaitak@mail.nih.gov 

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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

Authority and Regulations

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.

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