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 Neurological Disorders and Stroke (NINDS)
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Advancing Translational Sciences (NCATS)

Funding Opportunity Title

Network for Emergency Care Clinical Trials: Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) -  Clinical Coordinating Center  (CCC)  (U24)    

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices

  • April 14, 2016 - Notice of Pre-application Informational Webinar for the SIREN Clinical Trials Network. See Notice NOT-GM-16-106.
  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)

Funding Opportunity Announcement (FOA) Number

RFA-NS-16-014

Companion Funding Opportunity

RFA-NS-16-016, U24 Resource-Related Research Projects – Cooperative Agreements
RFA-NS-16-015, U24 Resource-Related Research Projects – Cooperative Agreements  

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

93.853, 93.839, 93.837, 93.838, 93.350 

Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to invite applications for the Clinical Coordinating Center (CCC) of Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN). SIREN will enable conduct of high-quality, multi-site clinical trials to improve the outcomes for patients with neurologic, cardiac, respiratory, hematologic and trauma emergency events. SIREN will consist of one Clinical Coordinating Center (CCC), one Data Coordinating Center (DCC) and up to 10 clinical centers (Hubs).  The CCC will facilitate implementation of clinical trials and will promote high quality and efficient timeliness in trial execution through such methods as master trial agreements and a central Institutional Review Board.  SIREN will implement a total of at least four large (>1,000 patient) simple, pragmatic clinical trials in the emergency department and pre-hospital settings. The clinical trials will be meritorious, peer–reviewed projects which will be awarded under separate funding announcements.

This FOA solicits applications for the Clinical Coordinating Center (CCC) for SIREN. Separate FOAs are issued to solicit applications for the clinical Hubs (RFA-NS-16-016) and the Data Coordinating Center (RFA-NS-16-015).   

Key Dates
Posted Date

March 9, 2016

Open Date (Earliest Submission Date)

May 1, 2016

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

June 1, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

October 2016  

Advisory Council Review

January 2017

Earliest Start Date

February 2017

Expiration Date

June 2, 2016  

Due Dates for E.O. 12372

Not Applicable

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.

There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

Problems accessing or using ASSIST should be directed to the eRA Service Desk.
Problems downloading forms should be directed to Grants.gov Customer Support.
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

The purpose of this funding opportunity announcement (FOA) is to solicit applications for the Clinical Coordinating Center (CCC) of the Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN).  SIREN will provide a robust  and readily accessible infrastructure for rapid implementation and high quality performance of clinical trials  in a breadth of emergency indications related to neurology (e.g., status epilepticus, traumatic brain or spinal cord injury, not cerebrovascular because StrokeNet is the primary network for stroke clinical research), cardiovascular (e.g., cardiac arrest, decompensation of cardiac failure), respiratory (e.g., respiratory arrest, pulmonary embolus), hematology (e.g., exsanguination) and trauma. SIREN will consist of one Clinical Coordinating Center (CCC), one Data Coordinating Center (DCC) and up to 10 clinical centers with their satellite sites (Hub and Spoke clinical site model).  The SIREN infrastructure should be sufficient for implementation at least four simultaneous large (>1,000 patient), simple, pragmatic trials in the Emergency Department (ED) and pre-hospital (e.g. transportation, EMS) settings. The purpose of SIREN is to advance emergency medicine by efficiently enabling performance of rigorous comparative effectiveness studies and assessments of novel therapeutic interventions.

Background

There is a clear public health imperative to stimulate and support research that improves care and clinical outcomes.  According to the Centers for Disease Control and Prevention (CDC), unintentional injuries are the leading cause of death for Americans under the age of 45.  In 2011, the most recent year with data published by the CDC, there were 136 million ED visits in the United States, accounting for about 4% of all health care spending.  Of the 136 million visits, 12%, or some 16 million, resulted in a hospital admission. About half of the top 10 reasons for presentation at an ED (i.e. chest pain, headache, cough, back symptoms, shortness of breath) are neurologic or heart, lung, blood (HLB) conditions and together these make up about 17% of all ED visits.

Clinical emergency care research covers all stages of the provision of emergency care, from pre-hospital emergency medical services to hospital EDs, trauma systems and emergency operative interventions. The principles of emergency care – making accurate and timely diagnoses and interventions– are independent of the disease, organ system and venue. The ED is the common entry portal for more than half of all hospitalized patients. Although dysfunction may start in one organ system, in a critical situation other organs can become rapidly involved, so successful care must address multiple systems. These characteristics of emergency care justify establishment of SIREN as a single, adaptable network able to support clinical trials in the multiple indications of neurology, cardiology, respiratory, hematology and trauma. 

Research Objectives

SIREN will harness multidisciplinary emergency care expertise to provide scientific leadership and the infrastructure required to conduct large, simple, pragmatic clinical trials to advance knowledge of optimal patient management in the prehospital and ED setting.  In addition, the network may be called upon to include other venues where post emergency care is provided (such as critical care units, the operating room or other hospital settings) when required by the needs of peer-reviewed, meritorious clinical trials.

The Clinical Coordinating Center (CCC) will contribute to these objectives by providing scientific and organizational leadership for implementation of clinical trials in SIREN. The CCC will promote high quality and efficiency in trial execution, and efficient timeliness through such methods as pre-negotiated master trial agreements and a single Institutional Review Board (IRB) by connecting the SIREN network to the CTSA program with its Trial Innovation Centers (TICs). The CCC additionally organizes the SIREN governance committees and oversees quality assurance for SIREN performance.  The CCC is encouraged to be innovative in improving clinical trial efficiency and quality.  

SIREN Organization

SIREN is funded by NINDS, NHLBI and NCATS, with NINDS as the lead institute. The Office of Emergency Care Research (OERP) and the Combat Casualty Care Research Program (CCCRP) in the US Army Medical Research and Materiel Command (USAMRMC) contributed their expertise during planning.  SIREN will consist of one clinical coordinating center (CCC), one data coordinating center (DCC) and up to 10 clinical center Hubs with their affiliated satellite clinical sites (“Spokes”), with the capability to coordinate clinical research in a large number of EDs across the United States.

The Clinical Coordinating Center (CCC) will provide scientific and organizational leadership to SIREN to achieve both efficiency and excellence in its implementation and performance of clinical trials. Responsibilities of the CCC will specifically include the SIREN central IRB, master contract agreements, with the clinical sites for trial performance, recruitment plans, enrollment tracking and quality improvement.  The role and responsibilities of the CCC are described more fully below (see Clinical Coordinating Center: Role and Responsibilities).

The Data Coordinating Center (DCC) will provide scientific and organizational leadership to SIREN in all aspects of data management, data quality, statistical design and statistical analysis.  Responsibilities of the DCC particularly include management and support of the Data Safety Monitoring Board(s) (DSMB), and reporting to regulatory authorities (e.g., central IRB, FDA).  The role and responsibilities of the DCC is described more fully in RFA-NS-16-015.

The Hubs will provide scientific leadership and conduct clinical trials in the ED and pre-hospital (e.g. ambulance, other transport) settings. A Hub is envisioned as a regional academic medical center or tertiary care facility which will enroll patients itself along with providing clinical and organizational leadership to its network of 2-10 satellite sites (Spokes). The Hub must be capable of providing physicians with expertise in emergency medicine, neurology, cardiology, pulmonology, hematology, general surgery, trauma surgery, neurosurgery, cardiovascular surgery or other subspecialties, as required. The roles and responsibilities of the Hubs and Spokes are described more fully in RFA-NS-16-016.

The CCC, DCC, Hubs and Spokes are each integral components of the network.  SIREN's success will require close, active cooperation and collaboration to assimilate these elements into a highly effective clinical research structure. Participants at all levels in SIREN are strongly encouraged to promote innovative methods to improve efficiency and quality in performance of emergency care clinical research.

Awards for the CCC, DCC and Hubs will be made through these three FOAs.   The FOAs (RFA-NS-16-014, RFA-NS-16-015, RFA-NS-16-016) will support cooperative agreements, under which the SIREN CCC, DCC, and Hubs will be expected to achieve agreed milestones and metrics, as described in each of the FOAs.  The baseline funding is purposefully lean, as it is anticipated that SIREN will additionally be supported by the individual clinical trial awards. Ideally, SIREN should have 3 to 4 clinical trials on-going during the second year of its five year term.  All participants in SIREN (CCC, DCC, Hubs) should actively stimulate and encourage the submission of clinical trial applications from the scientific community, including investigators within SIREN as well as others not affiliated with the network. Interested potential applicants are strongly encouraged to communicate with the Scientific/Research Contacts for this FOA regarding the processes and procedures for clinical trial grant applications at least three months prior to the planned submission date.

Clinical Trials Conducted In SIREN

With concordance of the funding NIH Institutes, clinical trials from other NIH or federal agencies which are relevant to emergency medicine may be conducted in SIREN.  Over the 5-year project period, SIREN is expected to implement at least four large (>1000 patients), simple, pragmatic clinical trials in the ED and pre-hospital (e.g., emergency medical services [EMS]) setting. The terms simple and pragmatic denote clinical trials which are consistent with and can be efficiently incorporated into standard emergency care. Typical features include brief, inclusive patient eligibility criteria, procedures which integrate easily into or with standard of care practices and limited, focused data collection.  Appropriate trials may test novel devices, medications or procedures or may compare effectiveness of existing therapeutic approaches.  Trials in SIREN will be hypothesis driven, not registries or descriptive observational studies.  

The clinical trials to be conducted in SIREN will be funded individually by project-specific grants from the participating NIH Institutes (e.g., NINDS, and NHLBI).    SIREN is intended as a multidisciplinary network reflective of the spectrum of clinical challenges confronted in emergency care. Collaborative projects that include disorders relevant to the missions of more than one of the participating institutes (i.e. NINDS, NHLBI,) will be strongly encouraged.  SIREN is not intended to be simply a neurology network or a cardiovascular network, and will conduct, in a fair and balanced manner, clinical research relevant to neurology and to heart/lung/blood. NCATS will facilitate coordination with and access to the CTSA network and is interested in collaborative projects that innovate the methods and tools needed for emergency care research.

Clinical trial applications may come from academic investigators (inside or outside of SIREN), investigators in military medical facilities, small business, industry, or other eligible institutions. SIREN may also be called upon to join or engage in other, on-going clinical trials in emergency medicine.  SIREN should be prepared to work collaboratively with other programs or networks, as a lead, partner or participant, as appropriate

Clinical Coordinating Center: Roles and Responsibilities

The CCC provides scientific and organizational leadership to facilitate the conduct of clinical trials within SIREN.  The CCC is the administrative center of SIREN, with responsibilities for contracts with sites for performance of clinical trials (master trial agreements with the clinical centers, other entities), planning budgets for proposed clinical trials, disbursing payments to sites, and managing the SIREN website. The CCC leads and manages the key SIREN governance committees: SIREN Steering Committee (SSC), SIREN Management Committee (SMC) and SIREN Operations Committee (SOC) (described below).  The CCC has primary responsibility for establishing and managing the central IRB.   The CCC is responsible for oversight of all aspects of trial enrollment and recruitment, from feasibility assessment, to planning, tracking and, if necessary, improvement plans.  The CCC also is responsible for quality assurance, related to clinical trials and to the overall performance of SIREN. The CCC will collaborate closely with the DCC (RFA-NS-16-015), the clinical research sites (RFA-NS-16-016), and the clinical trial PDs/PIs.

The goal of SIREN is to optimally implement each awarded emergency care clinical trial.  Since each clinical trial will be unique, the CCC must be flexible in providing tailored solutions. Examples of variations which may occur include, but are not limited to:

  • The number and identity of clinical sites will be different in each clinical trial. Hubs will participate in every study, but the Spokes will be selected based on the needs of the individual clinical trial.
  • Some clinical trials may include out of network ad hoc clinical sites, some of which could be international.
  • Some clinical trials may be performed in collaboration with other clinical networks.
  • Some clinical trials may include clinical venues besides the ED and prehospital setting, such as intensive care, hospital wards or outpatient clinics.
  • SIREN is intended for adult clinical trials, but some clinical trials might include children or adolescents, if appropriate for the disease under study;
  • SIREN might perform more than the currently projected four concurrent trials.
  • Applicants should discuss how they will manage challenges of flexibility and scalability.

Milestones will be determined at the time of award. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement (see Cooperative Agreement Terms and Conditions of Award).

Significant responsibilities of the CCC include the following:

a) SIREN Website will be an important tool for increasing awareness of SIREN and managing communication about and within SIREN.  The website should have a public section describing SIREN, giving instructions regarding clinical trial pre-application concept assessment procedures and providing ready access to public information such as on-going clinical trials, press releases and publications.  The website should also have a private section accessible only to SIREN and clinical trial personnel to facilitate communication about, though not limited to, SIREN committee meetings, metrics, and procedures.  The CCC is responsible for design implementation and maintenance of the SIREN Website. 

b) Master trial agreements. The CCC is charged with creating, negotiating and maintaining master trial agreements and subcontracts for performance of clinical trials directly with each clinical site (Hubs, Spokes, ad hoc sites) for all clinical trials conducted in SIREN.  NCATS will share example SOPs, templates, tracking software and support for the master trial agreements and subcontracts based on their utilization practices in the CTSA Trial Innovation Centers (TICs).  The CCC is encouraged to use the NCATS materials and the opportunity to confer with CTSA TICs to reduce duplication of effort and increase efficiency.  If an applicant has an alternative approach that would be superior in terms of efficiency and/or quality, this may be presented, along with rationale and justification, in the grant application. 

c) Centralized Budgets and Payments. For each clinical trial, the CCC will determine a budget with each clinical site (Hubs, Spokes and ad hoc sites).   The CCC will distribute funds directly to each participating clinical center. All payments will be on a per-patient basis, according to protocol budgets and the master trial agreement. The CCC is encouraged to create or adopt appropriate technology to facilitate and simplify these procedures. 

d) Central IRB. The CCC will be responsible for establishing and managing the central IRB for all clinical trials conducted in SIREN. The central IRB must include physicians and other health care providers with expertise in emergency and/or trauma medicine or surgery; ad hoc members with appropriate expertise may be added for individual clinical trials.  The central IRB must be capable of executing all requirements for review, approval and oversight of standard clinical trials.  Emergency care research may include Exception from Informed Consent (EFIC) studies,  with additional requirements for seeking community consultation and providing opt out provisions and public disclosure (see Exception from Informed Consent Requirements for Emergency Research, FDA, 2013 and 21 CFR 50.24).  The applicant should describe how the central IRB would conduct special requirements for EFIC trials, which might be accomplished through collaboration with local IRBs, through local community liaisons, local community representatives or other means. The central IRB should have the flexibility to accommodate potential variations in clinical trials, such as inclusion of pediatric age groups.   The CCC is responsible for completion of reliance agreements with the clinical center institutions (Hubs, Spokes and ad hoc sites), coordination of a central IRB of record, and management of all required IRB communication and documentation.  This includes but is not limited to maintaining documentation of IRB initial approvals, amendment approvals, site regulatory documents, communication with local IRBs or community organizations, adverse event reports, annual reports and reports related to EFIC requirements.

The CCC may elect to undertake to establish and manage the central IRB in collaboration with their institutional IRB or a duly constituted independent IRB.   NCATS will share SOPs, document templates, software tracking and management programs and other materials used to support the central IRBs in their CTSA Translational Innovation Centers (TICs).  The SIREN CCC is encouraged to harmonize methods with the TICs' central IRBs to decrease cost and time required for initiation of the SIREN central IRB. To facilitate interaction, the CCC Program Director/Principal Investigator (PD/PI will be invited to participate in TIC conferences and may confer with the TICs on best practices for central IRBs.  If an applicant has an alternative approach which would be superior in terms of efficiency and/or quality, this may be presented, along with rationale and justification, in the grant submission. 

e) Recruitment Plans and Patient Enrollment. The CCC is charged with oversight of patient enrollment for each clinical trial and in aggregate for each Hub and for the entire SIREN network.    Each clinical trial is required to have a detailed recruitment plan, with attention to adequate gender, race and ethnicity inclusion to assure that a valid analysis may be conducted at the conclusion of the trial.  The CCC, working with the clinical trial PI, should implement corrective actions if a clinical trial is not meeting enrollment expectations.  The CCC should also implement a corrective plan if a Hub is failing to meet its overall patient recruitment commitments to SIREN.  The CCC will also provide enrollment feasibility assessments for each clinical trial proposed to SIREN.

f) Quality Assurance. The CCC has specific responsibility for quality assurance in SIREN through creation and monitoring of specific, quantifiable performance metrics for itself, the DCC and the clinical sites.   These metrics should include, at minimum, start-up time, patient recruitment and retention, time from last patient's last visit to data base lock, and number and aging of data queries.  The CCC should preform quality reviews at least annually on itself, the DCC and the Hubs/Spokes, the results of which will be shared with the SIREN Steering Committee and the SIREN Federal Committee.  Innovative approaches to quality assessment and improvement are encouraged.

g) Clinical Trial Application Submissions.  The scientific value of SIREN will be realized through clinical trials conducted in the network.  Additionally, clinical trial grants will provide significant contributions to financial support of the infrastructure (i.e. CCC, DCC and Hubs), particularly during Years 2 - 5 of SIREN. The CCC must encourage and support submission of clinical trial applications from colleagues at their institution or elsewhere within the emergency medicine community.  The CCC PI and other members of the CCC research team are eligible to submit clinical trial applications that will be considered in the same manner as other applications, at any time during the existence of SIREN, including concurrently with this application for the SIREN CCC.  A concurrent clinical trial application is separate from this CCC FOA, and potential applicants are strongly encouraged to communicate with the Scientific/Research Contacts for this FOA regarding the processes and procedures for clinical trial applications.  The SIREN CCC application and the clinical trial applications undergo separate and independent merit review and award processes; success in one does not affect likelihood of success in the other.   

CCC Roles and Responsibilities in terms of leadership and SIREN organization include, but are not limited to:

  • Providing scientific leadership, particularly in relationship to clinical trial conduct and recognition of unmet needs in emergency care research.
  • Promoting visibility and awareness of SIREN and encouraging submission of clinical trial applications.
  • Coordinating and supporting all SIREN Steering Committee (SSC) (see SIREN Governance Committees below) and working group activities including, but not limited to, scheduling teleconferences and in-person meetings; arranging accommodations, transportation, facilities for in-person meetings; creating and maintaining documentation such as agendas and minutes; financial management including reimbursements.
  • Coordinating all SIREN Management Committee (SMC) and SIREN Operations Committee (SOC) meetings (see SIREN Governance Committees below), including but not limited to scheduling, creating and maintaining documentation such as agendas and minutes, communicating decisions to external parties.
  • Participating in the CTSA Network Executive Committee (NEC) activities
  • Developing SIREN Standard Operating Procedures (SOPs) that address all aspects of clinical trial implementation, recruitment and enrollment, quality assurance.
    • Including joint SOPs with the SIREN DCC;
    • Incorporating procedures or coordinating with SOPs from the CTSA Trial Innovations Centers (TICs) Overseeing from final protocol design to analysis/publication the implementation of at least four large (>1000 patients), simple, pragmatic multi-center clinical trials.
  • Providing  instruction and training to clinical sites  regarding Good Clinical Practices (GCP) and SIREN processes, procedures and metrics;
    • Clinical sites will include up to 10 Hubs that will participate in every clinical trial, 2-10 Spokes/Hub that will vary by trial, potential ad hoc non-network clinical sites, and prehospital providers (number will vary from trial to trial).
  • Providing a mechanism (e.g., call in center, hot line, web chat) for promptly addressing procedural queries from sites and prehospital providers, both for general SIREN processes and for processes specific to each clinical trial.
  • Monitoring human subjects' protection among participants enrolled at all SIREN clinical sites.
  • Providing general logistical support (e.g., facilities, travel reimbursements) to the DCC for Data and Safety Monitoring Board (DSMB) meetings, which will be held in conjunction with the in-person SSC meetings.
  • Coordinating study drug management, including but not limited to drug and placebo acquisition, delivery plan for bulk drug, secondary packaging/labeling/distribution/storage, coordinating stability testing and accommodating expiration timelines, and drug accountability, if required to do so, in a specific clinical trial.
  •  Proposing innovative methods and leveraging existing local research resources to enhance programmatic efficiency
    • Applicants are specifically encouraged to interact with CTSA, if present at their institution, to identify resources

The CCC and DCC, once selected for potential funding, will jointly submit their Standard Operating Procedures (SOPs) for SIREN to the NINDS and SIREN Federal Committee.  These will be revised from the individual versions originally submitted as part of their applications, and will present a collaboratively developed plan. They will also submit a scope of work document that details the division of tasks and responsibilities.  It is essential that the tasks required in planning and executing a complex, multi-center trial be clearly defined, and that the responsibilities of the collaborators (including CCC and DCC) be clearly delineated. It is therefore required that the joint DCC and CCC SOPs and scope of work document show excellent and seamless communication and coordination and reflect an in-depth understanding of the overall operational conduct of a complex, multi-center trial network.

The Responsibilities of the SIREN CCC in relation to clinical trials include, but are not limited to:

  • Rapid initiation of clinical trials;
  • Supervision of all aspects of patient recruitment, enrollment, retention, and disposition;
  • Financial management.

More specific detail follows, broken down by activities relevant to the progressive stages of clinical trial execution.

Prior to clinical trial application submission, during the pre-application phase of a clinical trial, the CCC is responsible for:

  • Providing information and guidance to all potential investigators as they apply for NIH funding for a clinical trial to be performed in SIREN (e.g., review protocol synopsis and schedule of activities, estimate need for additional trial-specific ancillary sites);
  • Ensuring that any required FDA approvals or documents (e.g., IND, IDE, IND exemption) are in place prior to grant submission;
  • Performing a feasibility study for enrollment and performance of the proposed clinical trial in  SIREN;
  • Developing a clinical trial budget that includes both per patient site costs and funds required to support SIREN infrastructure;
  • Supporting development of a draft clinical trial protocol or synopsis, including coordination of input from SSC, SMC and SOC (see SIREN Governance Committees, below).

After approval and award of a clinical trial, during the Planning Phase of approved clinical trials, the CCC is responsible for:

  • Supporting the clinical trial PD/PI and site investigators in finalization of the protocol;
  • Supporting the clinical trial PD/PI and site investigators in preparation of consent forms;
  • Supporting the clinical trial PD/PI and site investigators  through  central IRB review and approval;
  • Developing a written, detailed patient recruitment plan, with attention to adequate gender and minority representation;
  • Facilitating and monitoring the central IRB approval process;
  • Collecting regulatory documents (1572 forms, curricula vitae, Good Clinical Practice [GCP] certifications, etc.) from all clinical sites;
  • Finalizing details of per-patient payments to sites within approved budgets, developing site payment schedule, and finalizing contracts or subcontracts with sites per master trial agreements;  
  • Finalizing study drug packaging and labeling (if required for a particular clinical trial);
  • Holding investigator meetings and ensuring initial study personnel training for GCP and protocol adherence;
  • Supervising trial registrations on clinicaltrials.gov.

During the Enrollment and Data Collection Phase of approved clinical trials, the CCC is responsible for:

  • Overseeing the enrollment of eligible subjects;
  • Tracking enrollment and retention, and intervening if planned targets are not being achieved;
  • Includes tracking gender or minority enrollment  and intervening if these targets are not being achieved
  • Distributing study drug to centers (if required by a specific clinical trial);  
  • Ensuring appropriate protocol implementation, protocol adherence and Good Clinical Practices (GCP) compliance;   
  • Answering queries from the centers (e.g., application of inclusion and exclusion criteria, drug dose adjustments, handling adverse events, procedures for premature withdrawals);  
  • Conducting site visits, as needed;
  • Coordination activities with other networks or institutions, if applicable.
  • Distributing the approved per-patient payments to the Hubs, Spokes and ad hoc clinical sites   based on appropriate documentation received from each clinical center.  

During the Analysis and Publication Phase of each clinical trial, the CCC is responsible for:

  • Coordinating the communication of the trial results to the investigators, patients and public. If an EFIC trial, coordination of reporting results to the community. 
  • Publishing the primary and, if applicable, secondary manuscripts, in collaboration with the clinical trial PI and DCC.
SIREN Governance Committees

The success of SIREN requires collaboration and cooperation among its component parts and members.  Therefore, participation in the SIREN governance committees is an important responsibility.  The final governance structure will be determined with the participants after awards are made for the CCC, DCC and Hubs. The following proposed structure, based on that of other clinical trial networks, is provided as a guide for applicants to use in composing the research plan and budget of their application submission.

The SIREN Steering Committee (SSC) will be the main governing body. The responsibilities of the SSC include to: 1) provide scientific leadership in SIREN; 2) promote awareness of SIREN throughout the emergency community; 3) encourage and support development of clinical trial concepts and proposals for SIREN; 4) systematically assess clinical needs and goals for emergency care research. Membership and meeting frequency are outlined in the table entitled "SIREN Governance Committees". SSC meetings may include other ad hoc participants, such as research team members from the CCC, DCC, Hubs, Spokes, or clinical trials.

The SSC may establish SSC working groups or SSC subcommittees on an as-needed basis for specific functions, such as: 1) Support of CCC or DCC functions (e.g., developing per-patient budgets;  assuring quality control; monitoring conflicts of interest; developing data sharing policies; developing and standardizing per-patient budgets); 2) Development of  core competencies and technologies (e.g., imaging, ECG data analysis) educational materials); 3) Subject area working groups (e.g., neurology, cardiac, pulmonary, trauma) with attention to encouraging and developing clinical trial grants; 4) Working groups for allied health professionals (e.g., EMS,  study coordinators); 5) Advisory committees (e.g., patients and advocates, external experts); 6) Special topics ( publication plans, training/education materials)

The SIREN Management Committee (SMC) and the SIREN Operations Committee (SOC) oversee the day to day administration and operations of SIREN.  The first is more oriented towards strategic and administrative functions, the second towards operational and executional functions. Each clinical trial will have a Trial Committee, responsible for conduct of that particular trial; thus there are anticipated to be four Trial Committees.

Table: SIREN Governance Committees

Committee

Membership

Meetings

SIREN Steering Committee

CCC PD/PI (chair), DCC PD/PI, PD/PI or designee from each Hub

  • Monthly by phone or webinar, adjusted by SIREN activity and needs
  • Biannual face to face meetings in Washington DC metro area

SIREN Management Committee

CCC PD/PI (chair), DCC PD/PI, selected Hub PDs/PIs*

Weekly or biweekly by phone or webinar

SIREN Operations Committee

CCC PD/PI (chair), DCC PS/PI, selected CCC and/or DCC research team members, selected Hub PDs/PIs*

Weekly or biweekly by phone or webinar

Trial Committee

Clinical trial PD/PI (chair), CCC and DCC research team members (one of which should be either the CCC PD/PI or DCC PD/PI)

Monthly by phone or webinar, adjusted by activity and needs of trial

* Hub PDs/PIs or designees will serve on a rotating basis, with attention to balance across specialties (e.g., neurology, cardiology, trauma)

Federal oversight will be provided by the SIREN Federal Committee, which will consist of representatives from the participating Institutes funding the SIREN program of RFA-NS-16-014, RFA-NS-16-015, RFA-NS-16-016 (e.g., NINDS, NHLBI, and NCATS) along with expert consultation from the Office of Emergency Clinical Research (OECR).   NINDS is the lead institute for grants and funding for the SIREN infrastructure of CCC, DCC, and clinical Hubs. Each of the institutions on the SIREN Federal Committee will provide one member to participate on the SSC, SMC and SOC. Independent of the governance above, the respective NIH Directors retain oversight for all funded research from individual institutes or programs. The Directors’ authority overrides all SSC, SMC and SOC decisions.

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

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.

The following NIH components intend to fund up to 1 award which will be administered by NINDS.  The components intend to  commit up to the following amounts to direct costs in FY 2017:

  • National Institute of Neurological Disorders and Stroke (NINDS): $235,000
  • National Heart, Lung, and Blood Institute (NHLBI): $235,000;
  • National Center for Advancing Translational Sciences (NCATS): $100,000.
Award Budget

Application budgets should not exceed a maximum of $680,000 direct costs for Year 1 or $415,000 direct costs/year for Years 2-5 of SIREN.

Award Project Period

The maximum requested project period cannot exceed 5 years but the actual funded project period is dependent on reaching specific milestones as described in this FOA.  

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:

    • 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
  • 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 not 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.
  • 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

Only one CCC application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

Investigators at the CCC institution may apply for a Hub award (RFA-NS-16-016). A CCC and a Hub at the same institution should be led by separate PDs/PIs to ensure that the CCC activities and the local Hub activities each receive full attention.

Awards for a CCC and a DCC will not be made to the same PD/PI or institution to ensure that data analyses are performed independently.

Section IV. Application and Submission Information
1. Requesting an Application Package

Applicants must obtain 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.

2. Content and Form of Application Submission

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.

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:
      Robin Conwit MD

Telephone: 301-451-5939
Fax: 301-480-1080
Email: conwitr@ninds.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

For this specific FOA, the Research Strategy section is limited to 30 pages.

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.  In addition:

Facilities and Other Resources:

  • Specifically describe facilities and resources for the central IRB and reliance agreements..
  • Specifically describe facilities and resources available to support master contracts with Hubs, Spokes and other clinical sites.    
SF424(R&R) Senior/Key Person Profile

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

The PD/PI for the CCC will be a clinical trials expert who has successfully coordinated and implemented multicenter clinical trials. As support, applicants should provide evidence to demonstrate experience in:

  • Successfully coordinating and implementing multi-center clinical trials
    • Clinical trials in the ED and prehospital settings are most relevant;
    • Experience in neurology, cardiovascular, respiratory, hematology or trauma clinical trials, whether or not in the emergency setting, is also relevant.
  • Successfully designing multicenter clinical trials;
  • Successfully  working in a highly collaborative setting;
  • Encouraging and implementing innovative methods to reduce clinical trial duration and cost and to increase trial quality at their site;
  • Significantly contributing to Steering Committees or comparable governance committees;
  • Submitting clinical trial grants.
  • If applicants have experience with establishment and maintenance of central IRBs or with EFIC procedures, these should be indicated.    

Since the CCC PD/PI is the chair of the SSC, SMC and SOC, it is important that the PI have sufficient time to attend and actively contribute to these SIREN governance committee meetings (see SIREN Governance).

Applicants are strongly encouraged to name an experienced research team.  The applicants are encouraged to assemble a diverse team, that includes women and minorities.  The applicants are also encouraged to include young investigators or junior faculty, if appropriate. Members of the CCC research team are determined by the applicant, but typically might include:

  • Experienced study coordinators and/or project managers, potentially with areas of subspecialty such as recruitment or interactions with IRBs.  
  • Experienced financial coordinator or manager
  • Site Support Manager or comparable staff for training of all Hubs, Spokes and ad hoc clinical sites
  • Components of the central IRB, such as IRB chair, members, director
  • Liaisons to the IRB, clinical sites, CTSA TIC.

The PD/PI and members of the CCC team are encouraged to include references to their publications that highlight recently coordinated trials.

R&R Budget

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

  • The budget submitted for this FOA should reflect baseline costs needed to initiate, organize and maintain the CCC in a state capable of performing timely pre-application concept assessments and ready for rapid implementation of clinical trials. Salary support for the PD/PI and research team members should only include time spent on SIREN activities, which may include organizational/administrative tasks, support of individual clinical trials, and participation in SIREN governance and committee activities;
  • The budget should include travel costs for 1) PD/PI and two CCC team members to attend in person SCC meeting annually, 2) CCC PD/PI to attend a TIC Network Executive Committee (NEC) annually; 3) other travel related to SIREN operations.
  • The budget should not include tasks specific to each clinical trial since these will be awarded separately in the grant for that individual clinical trial.

Note: The budget submitted for this FOA should reflect baseline costs needed to initiate, organize and maintain the CCC in a state capable of performing timely pre-application reviews and ready for rapid implementation of clinical trials.  Funds for tasks specific to each clinical trial will be awarded separately in the grant for that individual clinical trial.

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:

Research Strategy: The Research Strategy must include the following Sections A – I.

A) Background and Experience

The applicant should include a description of current and up to 10 recently completed multicenter clinical trials. It is not necessary for the applicant to have led the trial or to have been a member of the CCC, though the applicant must clearly describe their role and contributions. The most informative and relevant examples would be clinical trials involving emergency care and/or performed in the ED or prehospital setting. Trials involving neurology, cardiology, respiratory, hematology, or trauma are also relevant. The summary may however include clinical trials on any disease supported by any funding source, if judged relevant by the applicant. Provide clear specific trial identification information (e.g., name, funding source, IND sponsor) along with disease/disorder and/or intervention under study.  Present specific performance metrics, including though not limited to:

  • the number and location of sites (US and/or other countries);
  • the number of patients;
  • the length of follow-up;
  • time to first contract/subcontract executed (starting from award date);
  • time to last contract/subcontract executed;
  • type of IRB (s)  and relationship to coordinating center site;
  • time to IRB at clinical coordinating center site;
  • time to first IRB approval at any consortium site;
  • time to last IRB approval at a consortium site;
  • time to first patient screened;
  • time to first patient randomized;
  • overall recruitment rate;
  • proportion of patients lost to follow-up;
  • proportion of patients missing data on primary or secondary efficacy measures;
  • type and frequency of protocol deviations;
  • time from last patient last visit to database lock;
  • time from database lock to completion of statistical analyses;
  • time from statistical analyses available until final draft of primary manuscript.

B) Leadership Plan

Demonstration of leadership capability is required for the CCC PD(s)/PI(s). It is also expected that, in order to successfully lead SIREN, the PD/PI already plays a leadership role in some capacity in the emergency care research community, which should be described in the application.

  • Leadership derives not only from the CCC PD/PI, but also from  members of the CCC research team.  A brief leadership plan should be presented which identifies and describes the roles of CCC personnel, along with how they will contribute to the success of SIREN.
  • The brief leadership plan should include a succession plan with identification of a substitute/back-up PD/PI candidate, if possible, to assure programmatic continuity.
  • Applicants should discuss their willingness and plans to organize, lead, attend and contribute to SIREN governance committees (see SIREN Governance Committee section) and provide examples of leadership and/or substantial contributions in comparable venues.  The CCC PD/PI should also attend and contribute to the TIC Network Executive Committee (NEC) annually in person and periodically by teleconference. 
  • Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner in all aspects of SIREN.  Applicants are encouraged to present prior examples of leadership in a comparably collaborative setting. 
  • Applicants should comment on any special expertise or unique strengths they can offer to leadership or collaboration within SIREN. 

C) Administration and Organization

  • The duties of proposed personnel responsible for day to day administration and operations at the CCC should be described. The organizational structure should be described with attention to how the structure will support optimal execution of the tasks in Clinical Coordinating Center: Roles and Responsibilities.  If there is prior experience operating as a team, this should be described.
  • The applicant should indicate how potential clinical trial investigators (from academia, military or industry) will be supported to work with SIREN  in the feasibility phase, and integrated into the network in the planning and implementation phases.
  • Success of SIREN will require strong communication and close collaboration.  The application should include a communication plan, which discusses:
    • communication with the DCC, and any experience with working in a CCC/DCC structure;
    • clinical sites (Hubs, Spokes, ad hoc sites) and pre-hospital providers, with attention to 1) general site training on SIREN processes; 2) clinical trial specific training; 3) mechanism for answering questions from sites; 4) mechanism(s);
    • clinical trial PIs;
    • The applicant is encouraged to be specific.  For example, a plan for clinical site training might include, though not be limited to, some of the following: 1) face to face and virtual venues for training (e.g., investigator meetings,  SSC meetings, site visits, webinars, teleconferences, newsletters); 2) planned target audiences  (e.g.,, study coordinators, prehospital providers); 3) potential topics of general importance (e.g., GCP, EFIC); 4) when or how certification or other means of training verification might be used; 5)  training  new site personnel  when there is staff turnover; 6) whether and how training should be repeated periodically during long duration clinical trials.
  • The SIREN Committees are key venues for organization and communication. The CCC PI chairs the SIREN Management and SIREN Operations Committees, and the CCC organizes and facilitates all SIREN meetings.  The application should discuss how the applicant proposes to optimally use these   committees to generate a coherent network identity, stimulate enthusiasm and ideas for emergency care research,   provide a forum for communication and education, and to execute tasks related to SIREN management and clinical trial execution. 
    • The applicant may propose changes to the committee membership or meeting frequency from that outlined in this FOA, with explanation of why these would be more effective.
    • More mundane aspects of meeting management, such as logistics, selection of topics, and preparation and distribution of minutes, should be covered.
    • The personnel responsible and existing support materials (e.g., templates, SOPs) should be identified.  Relevant SOPs may be included in an appendix.
  • The SIREN website may be an integral component of the communication plan and means for organizational management.  The applicant should discuss a plan for creation, maintenance and optimal use of the SIREN website, along with other communication and organizational tools.  The website plan should include design, contents, capabilities and integration into the larger organizational management plan.  The plan should also include logistical basics relevant to creation and maintenance of the website, such as availability and access to individuals with appropriate IT expertise and to required computer equipment.   

Operations: The application should describe the proposed CCC's standard operating procedures (SOPs) for clinical trial conduct and for administering and coordinating a network.

  • The PD/PI should document willingness to work with NCATS CTSA network and TICs on sharing methodology and SOPs for pre-negotiated trial agreements or subcontracts and central IRB, and should describe how these will be integrated into the CCC operations. Prior experience, if any, operating as a team should be described.
  • The ability of the proposed CCC research team to work in a collaborative and interactive manner with the Hubs, the DCC, the clinical trial PIs, the TICs, the SIREN Federal Committee should be discussed.

D) SIREN Financial Management: Master trial agreements, Per Patient Billing and Payments

  • The application should provide a summary of relevant prior experience and a plan for managing the financial aspects of SIREN.
  • Master trial agreement: Plans for negotiating, establishing and maintaining master trial agreements with each clinical site (Hub, Spoke or ad hoc site). Specific topics  may include 1) use of subcontracts for sites participating in multiple clinical trials (e.g., Hubs), 2) possible means for expediting or streamlining contracts for new sites participating in a clinical trial (e.g., new Spokes, or out of network sites), 3) experience of approaches with federal institutions (e.g., VA hospitals, military hospitals), 4) experiences or approaches with international institutions.
  • Per patient budgets: Plans for negotiating and maintaining for each clinical site.  Specific topics may include: 1) extent of standardization or harmonization across sites; 2) use for estimating clinical trial budgets; 3) incorporation of new sites.
  • Site payments: Procedures and mechanisms for site payments, including, but not limited to, 1) frequency, 2) mechanisms for triggering payments, 3) transfer of funds, 4) verification of receipt and 5) reporting to NIH. 
  • Consideration should be given to tools that may simplify procedures involving interaction with the sites, such as dedicated portals on the SIREN website or on-line budget calculators.
  • The financial plan should also include CCC central management approaches, such as tracking and archiving, reconciliation, error checks and planned audits, if any.
  • Challenges of managing Hubs and Spokes that are participating concurrently in multiple SIREN clinical trials should be addressed. 
  • The applicant should discuss their existing approach to financial management, including software, SOPs, templates or other tools. 
  • Applicants must document how they will obtain or access the legal and financial expertise for exemplary execution of the contracts, budgeting and payments. Any planned use of institutional resources (e.g., legal department, contract specialists, financial offices, IT support) should be clearly explained in the financial plan and must be documented in a letter of support from the institution. 
  • The applicant should discuss how they will leverage materials (SOPs, templates, software) and lessons learned from the CTSA TICs in setting up the SIREN CCC. 

E) SIREN Central IRB

Applicants should present any prior experience with establishment and management of central IRBs and/or performance of clinical trials under EFIC studies.  Applicants should discuss their (and, if appropriate, their institution's) willingness and ability to establish and maintain a central IRB for SIREN, consistent with specifics presented in CCC: Roles and Responsibilities.  The plan for the central IRB should include:

  • Establishing the central IRB;
  • Negotiating and maintaining reliance agreements with each clinical site (Hub, Spoke, ad hoc);
  • Mechanisms and procedures for serving as an IRB of record for routine clinical trials in SIREN;
  • Plan to establish, coordinate, review, communicate, document and report special EFIC procedures such as community consultation, opt out and public disclosure;
  • Willingness to work collaboratively with the CTSA TICs on procedures, SOPs and management of the central IRB, and integrate this collaboration into their central IRB plan.
  • Identification of potential IRB chairs, IRB members or key support personnel, such as an EFIC coordinator 
  • If the applicant plans to collaborate with an institutional IRB or independent IRB, the application should include: 1) the IRB roster; 2) any special modifications or accommodations for SIREN, such as addition of members with emergency care expertise or addition of administration staff; 3) how the institution will collaborate with NCATS TIC central IRBs.

F) Recruitment and Patient Enrollment

The PI should review prior experience with and present a plan which addresses specifics such as: 1) mechanisms for performance of recruitment feasibility assessments;  2) creation of clinical trial specific recruitment plans; 3) centralized support for materials (e.g., brochures, posters),  media (e.g., print, radio, TV, internet) and/or social media; 4) tracking enrollment accurately in real time during trial conduct; 5) creating corrective action plans, if needed. Tracking and corrective action plans for minority and gender enrollment should specifically be addressed. 

  • Plans should be described for interaction with the clinical sites (Hubs, Spokes, ad hoc sites) in terms of data collection, and identification and intervention at sites lagging in enrollment. 
  • Plans for collaboration and incorporation of the clinical trial PI should be outlined.
  • Describe the data resources that will be used for recruitment feasibility estimation (e.g., physician experience,   hospital or clinic charts, electronic records, specialized registry or data base).
  • Describe any particular tools or software that will be used or developed for recruitment, enrollment and/or feasibility. 
  • Describe the personnel responsible for recruitment and how their unique experiences and skills will increase successful patient enrollment in clinical trials conducted in SIREN.
  • Present examples of corrective actions for inadequate enrollment in aggregate or for subpopulations.  

G) SIREN Quality Assurance

  • The applicant should review experience with quality assurance and improvement, including design and implementation of quality improvement programs. The application should identify CCC personnel responsible for quality assurance and the means by which DCC, Hub and/or clinical trial PIs or personnel will be integrated into the quality process. Additional resources for quality assurance expertise should be identified. 
  • The application should include a quality assurance plan, which has identifiable portions for the CCC alone and for SIREN (CCC, DCC, Hubs).  This plan should include, though not be limited to: 1) specific, quantifiable metrics; 2) means of collecting this data, particularly from the DCC and Hubs; 3) performance and communication of findings of annual quality review (communication to SIREN Federal Committee as well as to DCC and Hubs); 4) proposed quality assurance besides the annual review (e.g., for cause site audits, on-going quality monitoring); 5) creation, communication, performance and verification of improvement plans; 6) creating incentives and enthusiasm for participation and compliance with quality assurance activities.
  • If the applicant has ever undergone a clinical or regulatory  audit as a CCC or clinical site, the results should be presented, along with implementation of any responsive improvement plan.  Relevant audits relate to clinical research and may have been conducted by NIH, FDA or industry

H) Promoting, Encouraging and Supporting Grant Applications for SIREN

The applicant should indicate how the CCC will promote awareness of SIREN, and stimulate submission of grant applications for clinical trials.   Applicants should discuss specific actions and how these will be accomplished within the first 1 – 3 years of the planned 5 year funding cycle.

Applicants should discuss their experience with submission of clinical trial grants, and under what circumstances they might participate or contribute to a grant submission for SIREN. If the applicant has already submitted or is concurrently submitting an application for an emergency care clinical trial to be conducted in SIREN in response to NOT-HL-15-262 or NOT-NS-15-039 this can be indicated;  any description of the proposed trial should be limited to one paragraph.

I) Innovations to Increase the Efficiency and Quality of the Clinical Research Enterprise

The CCC has the potential to promote the science and technology of the clinical trial process in general, as opposed to disease or indication specific interventions.  Creative and innovative approaches to increasing the efficiency and quality of clinical research are welcomed.  The applicant is invited to bring special attention to their constructive, innovative proposals and ideas and to describe how these would benefit SIREN itself or clinical research more generally.

Letters of Support: A statement of commitment from each participating institution or organization must be provided. At least one letter of support from the applicant's institution must be included in the application.  This letter should address how the general  institutional commitment will be established and sustained, how the institution will maintain accountability for promoting scientific excellence, and how the SIREN  effort will be given a high priority within the institution (relative to other research efforts and non-NIH supported programs.) The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the CCC director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution.  Institutions should document their willingness to commit to use of a master trial agreement and a central IRB, as described. If the Institution is committing facilities or resources to create, maintain or support the central IRB and/or master contracts, these should be presented in detail.  There may be multiple letters of support from the institution or its components, particularly if the institution is providing support of collaboration for specific CCC responsibilities, such as the central IRB or master contracting. At least one letter confirming institutional support should come from a high-level institution official(s) (e.g., Dean of the School of Medicine, Hospital President, and Vice President for Research).

If the central IRB will be in collaboration with the institutional IRB or a duly constituted independent IRB, the application should include a letter of support from the IRB chair. The letter should include any specific commitments of facilities or resources by the IRB (e.g., regulatory consultants, record storage space, computer software). If the proposed central IRB is an institutional IRB, senior institutional leadership should include the central IRB in their letter of support.

For those institutions with a CTSA or TIC, the applicants are encouraged to include documentation from the CTSA PD/PI regarding any support which will be provided to the CCC.  This may include access to or assistance from Recruitment (RIC) and Trial (TIC) liaisons at the CTSA. 

Additional letters of support are encouraged from key personnel and consultants, such as the proposed IRB chair, physician investigators, experts in recruitment or other CCC responsibilities or emergency care experts.   

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.

The following items are recommended for inclusion in the Appendix:

  • Sample documents that illustrate the CCC's expertise, such as policies, SOP's, etc.
  • One sample protocol and set of Case Report Forms (CRFs).
  • One sample study SOP describing regulatory document collection, IRB approvals, study drug management, procedures to minimize bias and maintain blinding, recruitment plans, retention plans, data sharing plans, safety monitoring plans, etc.
  • Examples of current SOPs for management of a clinical trial network.
Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.  

Post Submission Materials

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

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? Is there a strong scientific premise for the project? 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?

How will the proposed CCC contribute to the advancement of clinical research and clinical trials within the framework of SIREN?

Investigator(s)

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?

Does the application indicate that the PD/PI and research team have the appropriate experience to successfully lead, design and implement multicenter trials in SIREN? To what extent does the application show evidence of relevant experience in emergency care, neurology, cardiology, respiratory, hematology, or trauma?

Is there evidence to suggest that the PD/PI can build on an existing leadership role in the emergency care community to contribute to the success of SIREN? Is there evidence to suggest that the PD/PI and research team have appropriate experience to prepare them to form and manage a central IRB?  Is there evidence to suggest that the PD/PI and research team have appropriate experience to prepare them for SIREN financial management responsibilities (e.g., master trial agreements, budgets)? 

In what ways does the application suggest that the PD/PI can lead and contribute substantially to the SIREN governance committees (e.g., SIREN Steering Committee and subcommittees, SIREN Management committee, SIREN Operations committee)?  Does the application demonstrate that the PD/PI will have time to attend the meetings and teleconferences?

Is there evidence to suggest that the applicant will be effective and successful in promoting and encouraging submission of meritorious clinical trial grants for SIREN? Or might directly contribute to a clinical trial concept or proposal? 

In what way does the PD/PI's experience prepare him/her for leading and working in highly collaborative settings?

Is there assurance that the proposed research team and administrative personnel are qualified, capable and experienced?  In what ways will they increase the likelihood that performance will be exemplary at the proposed CCC?

To what extent do the performance metrics from past clinical trials (see Research Plan, A) support that the applicant would form an exemplary CCC?  Does the evidence support the ability to carry out the tasks enumerated under CCC: Roles and Responsibilities? 

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?

Does this application demonstrate that the proposed CCC will successfully manage master trial agreements, centralized trial budgeting and per patient payments, as planned in SIREN?

Does this application demonstrate that the proposed CCC will successfully form and manage an exemplary central IRB for emergency care? Does the application propose innovative methods for performance of EFIC studies under a central IRB?

Does the application demonstrate intent to creatively incorporate and leverage resources and expertise to be shared by CTSA TICs?  Is the proposed CCC poised to successfully collaborate, including possible harmonization of processes and procedures? 

Does the application provide evidence to suggest that the PD/PI or other members of the proposed research team could institute novel and innovative procedures that would increase efficiency and/or quality of clinical trial conduct in SIREN?

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 vertebrate animals or human subjects? 

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?

Does the application provide assurance that the proposed CCC will provide strong organizational focus for the CCC itself and for SIREN? 

Does the application present a communication plan that promotes collaboration and information sharing: 1) with the DCC; 2) with clinical sites (Hubs, Spokes, ad hoc sites, pre-hospital providers); 3) with clinical trial PIs?  In what ways does the communication plan provide assurance that the CCC will provide sufficient procedural training and will provide rapid, accurate resolution of questions/issues?  

Does the application present a financial management plan that will efficiently execute master trial agreements, per patient billing, and centralized site payments?  How appropriate are the expertise and personnel incorporated into the CCC and/or provided by the institution?

Does the application present a thoughtful and thorough plan for performance of the IRB tasks outlined in "CCC: Roles and Responsibilities" and Research Plan, E? How appropriate are the expertise and personnel incorporated into the CCC and/or provided by the institution?

Does the application present a plan for patient recruitment and enrollment, including feasibility assessments, trial specific recruitment plans and other components outlined in Research Plan, F, which will contribute to the success of SIREN? Does the application demonstrate awareness and realistic planning for achievement of minority and gender enrollment? 

Does the application evince strong concern for and adherence to high quality standards?  Does the application propose a plan for quality assurance and quality improvement for the CCC itself and for the SIREN infrastructure (DCC, Hubs) which will produce an exemplary and successful network?

To what extent does the application demonstrate that the proposed CCC will meet the challenges of flexibility and scalability required to meet the needs of the different clinical trials to be conducted in SIREN? 

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?

In the letters of support and commitment, what level and extent of commitment does the institution demonstrate for the PI (may be expressed as additional protected time, departmental research leadership position, facilities, space, or resources)?

If the proposed CCC intends to use or collaborate with the institutional IRB or with an independent IRB, how strongly does the institution/independent IRB support the success of the SIREN central IRB? To what extent is support expressed in terms of access to personnel and resources?   

If the proposed CCC intends to use or collaborate with the institution on financial management (e.g., master trial agreements, centralized budgets, centralized payments), how strongly does the institution support the success of this aspect of SIREN? How well is this support expressed in terms of access to personnel and resources?

Does the application, including the letters of commitment and support, indicate any institutional hesitations or barriers which would limit the ability of the CCC to collaborate and/or harmonize processes with the CTSA TICs?

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.

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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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 NINDS, 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.

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

Applications will be assigned  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 Advisory Neurological Disorders and Stroke Council. 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.
  • Clinical trial expertise, track record, and resources.
  • Strong track record of successful collaboration and participation in large, multi-center research teams and willingness to work collaboratively, including with other components of SIREN and the CTSA TICs.
  • Willingness and evidence of ability to participate in all aspects of the SIREN program, including the SSC, SMC, SOC, Trial Committees, SSC working groups, and participation in teleconferences and in person meetings.
  • Current and/or successfully completed NINDS or NHLBI- funded clinical emergency care projects at the applicant’s institution.
  • Ability to begin operations in February 2017;
  • Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI.2.A).
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.

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:

  • Organizing and managing SIREN infrastructure including establishment of a central IRB and mechanisms for master trial agreements and centralized budgets and payments, managing SIREN governance committees,  implementing  SIREN clinical trials ( including GCP and other regulatory requirements, overseeing recruitment and retention, overseeing quality), reporting to the SIREN Federal Partners, and working collaboratively working with the DCC and Hubs.  
  • The CCC PI is expected to chair the SSC, SMC and SOC, and to participate in other SIREN committee meetings and clinical trial investigator meetings.
  • 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 NIH staff in collaboration with the SIREN Federal Partners will work with the SIREN investigators to develop performance milestones for the CCC. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement.
  • An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
    • Cooperation or coordination with, or assistance to, awardees in performing project activities, e.g., development of research protocols; data collection, analyses, and interpretations; re-establishment of objectives during the course of a project;
    • Providing for an option to halt a project activity if technical performance requirements are not met or if program objectives have already been met;
    • Assistance with the selection of contractors or sub-awardees and in the selection of key project personnel other than PD/PI;
    • Technical monitoring to permit specific direction of the project, including recommending approval of changes in technical approaches;
    • Participation on committees  as a voting member or in other functions responsible for helping to guide the course of SIREN; and
    • Participation in the presentation of research results, including publications from the project.
  • In addition to the Project Scientist, an NIH Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

  • Participation on SIREN committees, specifically the SIREN Steering Committee (SSC), and its working groups and subcommittees, SIREN Management Committee (SMC), the SIREN Operations Committee and Trial Committees (see SIREN Governance Committees).

Clarifying, negotiating and finalizing the milestones and timelines.

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.

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.

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: http://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 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: 301-435-0714

Scientific/Research Contact(s)

Robin Conwit, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: conwitr@ninds.nih.gov

George Sopko, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0504
Email: sopkog@nhlbi.nih.gov

Todd Wilson
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0768
Email: twilson@mail.nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Tijuanna DeCoster, PhD, MBA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@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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