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 Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title

Clinical Trials Units for NIAID Networks (UM1)

Activity Code

UM1 Multi-Component Research Project Cooperative Agreements

Announcement Type

Reissue of RFA-AI-05-002

Related Notices

RFA-AI-12-001; RFA-AI-12-004; RFA-AI-12-008; RFA-AI-12-011; RFA-AI-12-012; RFA-AI-12-019

Funding Opportunity Announcement (FOA) Number

RFA-AI-12-018

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.855, 93.856  

Funding Opportunity Purpose

The purpose of this FOA is to solicit applications for Clinical Trials Units (CTUs) for NIAID clinical research networks focused on the following six research areas:  1) Adult HIV therapeutic strategies, including HIV cure, noninfectious comorbidities, and the infectious comorbidities of hepatitis and tuberculosis; 2) strategies to address HIV and HIV-associated infections in pediatric and maternal populations; 3) integrated HIV prevention strategies; 4) microbicide strategies to prevent HIV infections; 5) vaccines to prevent HIV infections; and 6) strategies to address antibacterial resistance.

Key Dates
Posted Date

April 10, 2012

Letter of Intent Due Date

December 29, 2012

Application Due Date(s)

January 29, 2013   

AIDS Application Due Date(s)

Not Applicable. 

Scientific Merit Review

July, 2013   

Advisory Council Review

January, 2014 

Earliest Start Date(s)

May, 2014

Expiration Date

January 30, 2013 

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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

1.  Purpose

The purpose of this FOA is to solicit applications from domestic and foreign institutions to serve as Clinical Trials Units (CTUs) for NIAID clinical research networks focused on the following six research areas: 

1.  Adult HIV therapeutic strategies, including HIV cure, noninfectious comorbidities, and the infectious comorbidities of hepatitis and tuberculosis;

2.  Strategies to address HIV and HIV-associated infections in pediatric and maternal populations;

3.  Integrated HIV prevention strategies;

4.  Microbicide strategies to prevent HIV infection;

5.  Vaccines to prevent HIV infection; and

6.  Strategies to address antibacterial resistance. 

The establishment of a Clinical Research Network on Antibacterial Resistance presents a new opportunity for NIAID to leverage HIV/AIDS CTUs and Clinical Research Sites (CRSs) to expand clinical research on the pressing problem of antibacterial resistance. 

The development, implementation and adaptation, as needed, of the clinical research program of each clinical research network will be managed through separate awards to establish and maintain Leadership Groups (LGs).  The NIAID has previously solicited applications for Leadership Groups through separate FOAs.  Each Leadership Group (LG) will be comprised of a Leadership and Operations Center (LOC), a Laboratory Center (LC), and a Statistical and Data Management Center (SDMC).  The association of the CTUs and their CRSs along with the LG will constitute the clinical research network.  NIAID expects to fund a minimum of 25 CTUs in order to support the research agendas of the clinical research networks.

The CTU is the nucleus of clinical research activity for the clinical research networks. It is an organization/institution responsible for the coordination and execution of clinical trials in accordance with clinical research network, NIAID and other applicable policies. The CTU is composed of multiple components including:

1.  CTU administrative office

2.  At least one, but no more than eight (8) domestic or international CRS(s)

3.  Community Advisory Board(s) (CABs)

4.  Pharmacy(ies)

5.  Laboratory(ies)

6.  Other clinical research activities (including but not limited to data management, quality management, regulatory assurance and training)

The CTU provides the scientific and administrative expertise as well as the infrastructure to participate in two or more NIAID HIV/AIDS clinical research networks.  CTUs may also propose to be part of the Clinical Research Network on Antibacterial Resistance, but such affiliation is not required.  Each CTU must demonstrate sufficient breadth and depth of scientific expertise to contribute to the ongoing refinement of the clinical research network(s) agenda, participate in an array of scientific studies, and demonstrate a productive partnership with the community(ies) in which they propose to conduct research.  The CTU Administrative Office is responsible for managing all CTU resources and overseeing the performance of its associated components including CRS(s), local laboratory and pharmacy functions as defined below.  A CRS is a component of a CTU and is defined as a discrete location (e.g. hospital, outpatient clinic, community health center, private practice, local health department clinic) with appropriate, identified and characterized potential trial participants (e.g. demographics, incidence and prevalence of HIV/AIDS) where participant recruitment and retention, protocol management and other clinical research activities are conducted. 

A priority is placed on reaching populations severely impacted by the HIV/AIDS epidemic whose participation will help address priorities for NIAID HIV/AIDS research.  These populations include, but are not limited to women, adolescents and minorities in the United States as well as populations in low and middle-income countries. CTUs with the flexibility and capability to conduct multiple clinical research projects, the ability to respond rapidly to evolving research opportunities, and the capacity to participate in the development and implementation of the clinical research plans of multiple NIAID clinical research networks are particularly sought.  

2. Background

Over the past 30 years, HIV/AIDS research has led to phenomenal scientific advances.  Scientists uncovered the structure and genetic organization of HIV and began to understand the mechanisms by which HIV causes disease.  This understanding led to the development of (i) tests to detect HIV infection, measure HIV viral load, and monitor immune function, and (ii) highly active antiretroviral therapies (HAART).

Despite these scientific advances, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 34 million people globally are estimated to be living with HIV, and 22.5 million of these are living in sub-Saharan Africa.  Slightly more than half of all people living with HIV are women and girls.  In sub-Saharan Africa, more women than men are living with HIV, and young women aged 15–24 years are as much as eight times more likely than men to be HIV-infected.  HIV/AIDS continues to be responsible for approximately two million deaths each year.

Researchers from the CTUs and associated CRSs have supported the development of NIAID-funded HIV/AIDS clinical research networks and their diverse agendas. The success of the networks to date has relied heavily on the scientific expertise and leadership contributions of the CTUs and associated CRS personnel. 

The NIAID currently directly funds 72 CTUs comprised of approximately 160 CRSs worldwide.  Each CTU participates in one to five of the existing six HIV/AIDS clinical research networks, and collectively have enrolled over 74,000 participants in Phase I, Phase II, Phase IIb, and Phase III observational and interventional studies through November 1, 2011.  The CRS distribution has been predominantly reflective of the communities most heavily impacted by the HIV/AIDS epidemic.

CRSs have recruited participants from diverse populations to support the research agenda of the NIAID HIV/AIDS clinical research networks. By November 1, 2011, the current CRSs had enrolled over 20,000 participants into HIV pediatric and adult therapeutic studies in 20 countries.  Data generated from these studies have contributed to the development of international guidelines for HIV treatment and have improved the clinical management of HIV infection and its co-morbidities.  CRSs have also enrolled over 6,700 participants into HIV vaccine prevention studies in 11 countries. In addition, CRSs have enrolled over 10,000 participants into microbicide HIV prevention studies and over 8,000 participants into other non-vaccine HIV prevention studies which led to the successful development of integrated, behavioral and biomedical prevention models.

Many CRSs have been able to effectively enroll and retain participants in large multi-center clinical trials.  For example, one significant microbicide study titled, “Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel (P) for the Prevention of HIV Infection in Women” (HPTN 035), evaluated the effectiveness of two topical microbicides, BufferGel and 0.5% PRO 2000 compared to placebo gel and a no-gel study arm.  This Phase II/IIb clinical trial was conducted at 9 CRSs in Africa and the US and over 3,000 participants were enrolled with a retention rate of 94%.   

The CTUs have contributed to several high- impact, ground breaking research studies.  For example, the study titled, “A Randomized Trial to Evaluate the Effectiveness of Antiretroviral Therapy Plus HIV Primary Care versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in Serodiscordant Couples” (HPTN 052) evaluated the treatment and prevention benefits of early versus standard initiation of ART among serodiscordant couples in 8 countries in Africa, Asia, and South America. The study revealed a 96% benefit in preventing HIV infection of the uninfected partner when the infected partner initiated ART immediately compared to these who delayed ART.

The CTUs have been able to respond rapidly to emerging needs of the clinical research networks.  For example, in 2009, NIAID, through the IMPAACT network, quickly initiated two clinical studies enrolling over 200 participants in 3 months, that determined that the 2009 H1N1 influenza vaccine could safely elicit a protective immune response in HIV-infected pregnant women and children. 

The CTUs have also been effective in engaging constituents representing the needs and research priorities of the communities that they represent primarily through the use of Community Advisory Boards (CABs) working with the CRSs. CABs consist of volunteer representatives from the communities in which the research is conducted. During the stages of protocol development, implementation and close-out, CTUs actively engage their CABs and other community stakeholders in dialogue to ensure that the protocols are representative of and reflect the priorities and needs of their communities.

In summary, the CTUs have played a significant role in HIV/AIDS clinical research in the areas of both treatment and prevention.  The accomplishments of the CTUs have contributed to improved clinical management of HIV infection throughout the world through the identification of more effective therapies and treatment strategies, as well as new strategies to prevent the spread of HIV.

3. CTU Structure and Function

Clinical Trials Units.  Clinical Trials Units provide the scientific and administrative expertise as well as the infrastructure to support the NIAID clinical research networks.  A CTU is an organization/institution composed of multiple components, including:

The CTU must reflect a cohesive, integrated unit and participate in at least two NIAID HIV/AIDS clinical research networks.  An optimal CTU configuration will support participation in multiple clinical research networks, promote efficient utilization of resources and infrastructure, and include continuous performance evaluation. The CTU will assume the network affiliations of its component CRSs.

In addition, CTUs may participate in the Clinical Research Network on Antibacterial Resistance, but such participation is not required.

The CTU must have sufficient space (facility), dedicated staff and institutional commitment to ensure organizational stability and fulfill the CTU’s objectives. The CTU composition including the location of the CTU administrative office, location of CRS(s), number of CRS(s), scope and complexity must be commensurate with the scientific diversity and the clinical research networks in which the CTU proposes to participate.  The NIAID recognizes that the scientific contributions of the CTU Principal Director/Principal Investigator (PD(s)/PI(s)), CRS Leaders, and Investigators are essential in developing and carrying out a strong, high priority research agenda for each clinical research network.  If there are multiple PD(s)/PI(s), the level of effort of each PD/PI must be commensurate with the size and scope of the CTU.  The CTU PD(s)/PI(s) is/are responsible for all CTU activities and CTU performance, and may also serve as the primary scientific and administrative representative(s) to the clinical research network(s).  The CTU is expected to coordinate and collaborate with the LOCs to ensure performance monitoring and evaluation of sites. The day-to-day operations of the CTU must be overseen by a CTU Coordinator with relevant management and clinical research experience and qualifications.

CTU Administrative Office.  The CTU Administrative Office provides oversight, coordination, fiscal management, and administrative support for all activities of the CTU.  CTU Administrative Office staff may also contribute to the clinical research network agenda and priorities through activities such as scientific and resource committee membership or protocol team membership. 

Clinical Research Site.  A Clinical Research Site (CRS) is a component of a CTU and is defined as a discrete location (e.g. hospital, outpatient clinic, community health center, private practice, local health department clinic) with appropriate, identified and characterized potential trial participants (e.g. demographics, incidence and prevalence of HIV/AIDS) where participant recruitment and retention, protocol management and other clinical research activities are conducted.  The CRS must be staffed by qualified professionals capable of conducting clinical research for one or more clinical research networks in accordance with Good Clinical Practice (GCP), local regulatory requirements, and other applicable NIH requirements.  In addition, each CRS must participate in one or more NIAID HIV/AIDS clinical research network(s).  The activities of each CRS will be directed by a CRS Leader with the experience and qualifications to oversee clinical activities and the day-to-day clinic operations will be overseen by a CRS Coordinator with relevant clinical research experience and qualifications.  An individual CRS and/or CRS Leader may be proposed in only one CTU application. 

The number of CRSs at any one institutional location (e.g. hospital or medical campus) should be limited to the number required to provide appropriate and cost-effective clinical research oversight for diverse populations (e.g. pediatrics, adult medicine).  However, it is expected that each institutional location will have no more than one CRS for each of the diverse populations.  Where practical and efficient, applicants are encouraged to combine the operations of diverse populations into one CRS.

In addition to the CRSs listed in the application, there may be future opportunities to bring on limited protocol-specific (PS) sites to meet the needs of a particular protocol during the project period.  These PS sites will be identified by the clinical research network, CTU, or NIAID to meet a discrete need; for example, to accomplish protocol-specific recruitment goals, if the capacity does not exist at currently funded CRSs.  These PS sites will be scheduled to close, and funding discontinued, upon completion of the specified protocol activities, unless the clinical research network requires the PS site to meet additional, identified, appropriate protocol activities.  Protocol-Specific sites should not be named in this application.  Protocol-specific sites will be identified and proposed after award, based on identified protocol-specific clinical research network needs.

Community Advisory Board(s) (CABs).  Each CTU must develop and implement a plan for forming and maintaining a productive partnership in the communities in which clinical research will be conducted. This partnership may be facilitated through a CAB.  A CAB is an active group of individuals representing the local population(s) impacted by HIV/AIDS. The organization and composition of each CAB should reflect local community representation, promote community engagement, and provide local perspective(s) on the implementation of the NIAID clinical research plan(s).  The CTU must determine how best to organize community partnerships to meet the research needs and priorities of the local population.  This may include multiple CABs if required to enable effective representation of the populations involved, for example, to represent geographically, culturally, or other distinct populations. 

Considering the overall CTU budget, CTUs shall provide support, including but not limited to reasonable costs for CAB meetings and associated expenses. CTUs will also be expected to provide reasonable accommodation, access to trainings, local engagement activities and other means of educating and/or engaging the CAB and community at large.

Laboratory.  Each Leadership Group (LG) has a network laboratory center (LC) which leads the laboratory activities that are required to carry out the clinical research network agenda.  In addition, each CRS must have access to a local laboratory capable of protocol-specified testing, as well as specimen processing, laboratory data management capabilities, shipment and storage of samples collected at the CRS.  The local laboratory must be capable of communicating efficiently with the network LC. The CTUs may elect to utilize as appropriate, local laboratory services such as hospital clinical pathology departments and commercial laboratories, or provide laboratory services within the CTU.  When practical and efficient, CTUs may utilize a single laboratory to support multiple CRSs.  Laboratories must meet and maintain specific requirements to ensure compliance with Good Clinical Laboratory Practice (GCLP). 

Pharmacy.  Each CRS must have access to a secure pharmacy facility staffed by qualified pharmacist(s) in order to receive, store, manage inventory, dispense study product, and maintain accurate records in accordance with GCP, applicable United States regulations, NIAID guidelines and local requirements/regulations.  The CTUs may elect to utilize appropriate pharmacy services, such as a research pharmacy operated by a medical facility, or provide pharmacy services within the CTU.  When practical and efficient, CTUs may utilize a single pharmacy to support multiple CRSs.  The Pharmacist(s) of Record (PoR) is/are responsible for overseeing all pharmacy-related activities. 

Other Clinical Research Activities.

4. Core and Protocol Funds

 Funding to carry out the network’s clinical research agendas falls into two categories:

1.  Core Funds.  NIAID will provide core funds directly to the CTUs on an annual basis to support the Administrative Office and other CTU components.  Each CTU will receive core funding at a level sufficient to maintain a limited staff and infrastructure.  CTU core funds will be determined by NIAID based upon the size and scope of the funded CTU.  For example, a CTU participating in 2-3 NIAID HIV/AIDS clinical research networks and comprising 3-4 CRSs may expect core funding within the range of $1.2M-$2.0M total costs.  The amount will be adjusted based on the size/scope of the CTU.

Core funds include (but are not limited to) minimal support for the following activities: 

Core funds are not intended to cover 100% of these expenses.  Core funds do not include expenses directly attributable to the development, approval, or conduct of specific clinical trials. CTU core funds will be supported by NIAID funds; however, applicants are encouraged to develop collaborations to enhance utilization of existing resources.

Core funds will be provided at the time of award.

2.      Protocol Funds (PF).  This category of funding provides additional support to the CTU to cover protocol-related expenses attributable to protocol development, implementation or close-out of a clinical trial. 

Following discussions between the NIAID and the network LOC, the NIAID will determine the amount of PF required to support each CRS’s participation in an approved protocol.

Protocol funds include (but are not limited to) the following protocol-specific expenses:

When it is determined that the PF is needed in addition to core funds to carry out the clinical research network’s research agenda, funds may be distributed by one of the following: 

Each CTU applicant must be able to administratively accommodate both routes for PF distribution in their financial management structure to ensure prompt and efficient budget allocation to their component CRSs.  If the clinical research network uses route 2 above for PF distribution, the CTU PD(s)/PI(s), in consultation with the CRS and NIAID, will determine whether the CRS is capable of receiving PF directly from the LOC or whether the PF will be routed through the CTU Administrative Office to the CRS. 

The CTU Administrative Office has primary responsibility for PF accounting for all CTU components, regardless of the method of PF distribution, and is responsible for providing funding information to the NIAID and the affiliated clinical research network(s).

Protocol funding will be determined post-award and should not be requested in response to this FOA.

For those CTUs also proposing affiliation with the Clinical Research Network on Antibacterial Resistance, protocol funding will be disbursed directly from NIAID into the CTU grant awards.  In addition, for some clinical research, CTUs may receive protocol funds directly from the Antibacterial Resistance Leadership Group.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIAID intends to commit up to an estimated total cost of $70M in FY 2014.

Award Budget

Application budgets are not limited, but need to reflect actual needs of the proposed project based on the size/scope of the CTU.  For example, a CTU participating in 2-3 NIAID HIV/AIDS clinical research networks and comprising 3-4 CRSs may expect core funding within the range of $1.2M-$2.0M total cost..

Award Project Period

The maximum period is 7 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions 

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

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.     

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applications proposing participation in fewer than two NIAID HIV/AIDS clinical trials networks will not be responsive and therefore not reviewed.

Applications proposing more than eight CRS will not be responsive and therefore not reviewed.

Each CRS may be proposed in only one CTU application.

A CTU PD/PI may only be proposed in one CTU application.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, 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.

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:

The letter of intent should be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (for Express Mail – 20817)
Telephone 301-496-8426
FAX: 301-480-2310
Email: pjackson@niaid.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three  signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (for Express Mail – 20817)
Telephone 301-496-8426
FAX: 301-480-2310         
Email: pjackson@niaid.nih.gov

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following requirement:

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Supplemental Instructions for the Preparation of Linked Multi-Component Application

Applicants should incorporate the following deviations from the PHS 398 instructions noted under the specific headings below for the multi-component UM1 application.

Use the table below as a supplemental guide to PHS 398 form Page 3 to assemble the multi-component UM1 application. 

Item

 

Face Page. This is the first page of the application; number all succeeding pages consecutively. There is one face page and it covers the entire CTU.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells statement if applicable. This is for the entire CTU.

Detailed Budget for Initial Budget Period. Proposed budgets for the first Year for core costs only, not any requests for protocol funds (PF).

Budget for Entire Proposed Period of Support This is the Composite Budget for all years of Proposed Support.

Budgets Pertaining to Consortium/Contractual Arrangements Detailed Budgets for Consortium Agreements should be provided as a separate page and summed as a line item on PHS 398 Form Page 4.

Research Plan

Specific Aims for the entire CTU

Note:  For each component below, include a Cover Page and other information as described under detailed component headings.  Do not use PHS 398 Form Page 1 for individual components. 

Component 1. CTU Research Overview

Component 2. CTU Administration

Component 3. Financial Resource Management

Component 4. Communication

Component 5. Evaluation

Component 6. Community

Component 7. Pharmacy

Component 8. Laboratory

Component 9. Other Clinical Research Activities

Component 10. Clinical Research Site(s) (CRS)

NOTE:  label each individual CRS described with a number and letter combination (10A, 10B, 10C, etc.).

Component 11. Clinical Research Network on Antibacterial Resistance

Biographical Sketch (Biographical Sketch Format Page). Provide biographical sketches of all senior/key professional personnel for all components at the end of the application.  Place PD(s)/PI(s) biographical sketch first, followed by those of other key personnel (CTU Coordinator, CRS Leader, CRS Coordinator, Pharmacist(s) of Record) in alphabetical order.

Resources. Complete the resources available for each component.

Checklist

Appendix


Component 1.  CTU Research Overview

Research Strategy (Limited to 30 pages):  Organize this section in the order specified in the PHS 398 Instructions Section 5.5.3. Make sure to start this component with the appropriate section heading in order, addressing Significance, Innovation, and Approach, including the appropriate information.

Summarize the proposed scope of research to support the scientific priorities of the clinical research networks the CTU is proposing to join.  Describe (i) the potential trial participants the CRS(s) can access (e.g., demographics, incidence and prevalence of HIV/AIDs); (ii) the proposed approach to integrating functions within each of the scientific areas proposed and across the entire CTU; and (iii) how the CTU will position itself to respond to emerging scientific priorities of proposed clinical research networks. 

Performance and Applicant Experience. Within the Approach section, for renewal applications, (i) expand upon past performance of the CTU over the previous 5 to 7 years; (ii) identify strengths and areas for improvement; and (iii) provide improvement plans.  For new applications, provide the information identified above related to a clinical trials program of similar scope and complexity in this area of research during the past 5 to 7 years.

Network Participation.  (i) Provide justification for the proposed research areas. (ii) Describe prior relationship(s) between CTU component parts and summarize outcomes, and/or planned collaborations and anticipated value.

Provide a table as shown below with relevant information including the name of the CTU PD(s)/PI(s), name of each proposed CRS, the CRS leader and identify each CRS network(s) affiliation.

CTU PD(s)/PI(s) (1 or more)

CRS Name

CRS Leader (1 per CRS)

Clinical Research Network on Therapeutics for HIV/AIDS and HIV-associated Infections in Adults

Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations

Clinical Research Network on Integrated Strategies to Prevent HIV Infection

Clinical Research Network on Microbicides to Prevent HIV Infection

Clinical Research Network on Vaccines to Prevent HIV Infection

CRS 1

Dr. A

X

X

CRS 2

Dr. B

X

CRS 3

Dr. C

X

X

CRS 4

Dr. D

X

X

X

X

X


Scientific Leadership.
  (i) Identify PD(s)/PI(s) and other relevant CTU scientific leadership. (ii) Describe the scientific experience and knowledge of the PD(s)/PI(s), CRS Leader(s), and Investigator(s) including relevant contributions to the field(s) of research proposed. (iii) Provide justification for proposed PD(s)/PI(s). (iv) Describe how scientific leadership will be provided within the CTU and to the NIAID clinical research networks.  Summarize the proposed approach to making high level scientific decisions including selection of protocols, as well as reassessment and redirection of resources to support the scientific priorities of the proposed network(s). (v) Describe the plan for CTU staff to contribute to the development of the network clinical research plans through activities such as membership on protocol teams, scientific and resource committees, and scientific review of proposed concepts and protocols.

Applicants are encouraged to draw upon their past experiences with participation in HIV/AIDS multicenter clinical trials or equivalent experience. 

Component 2. CTU Administration (Limited to 12 pages)

Structure and Governance

Institutional Commitment/Support

Component 3. Financial Resource Management (Limited to 6 pages)

Describe (i) the financial management structure, including the duties, responsibilities, experience, and time commitment of essential staff;  (ii) policies and procedures for establishment and implementation of consortia agreements, including timelines and responsible parties; (iii)  prior experience managing complicated funding streams; (iv) how resource utilization will be monitored and adjusted as needed; (v) the process for allocating resources to each CRS in a transparent manner;  (vi) the plan to provide timely financial status information to the LOC and NIAID, including all funding sources to the CRSs; (vii) criteria used to determine whether CRSs have the capability to receive protocol funds directly from the LOC, and (viii) which CRSs, if any, have the ability to receive protocol funding directly from clinical research networks (refer to Part II, Section 1.4 for description of both funding models).

Component 4. Communication (Limited to 6 pages)

Describe proposed CTU communication and collaboration plans, including the roles and responsibilities of involved individuals related to performance expectations, consequences for poor performance, site selection and resource allocation.  Describe how the CTU will establish and maintain clear lines of communication and procedures within the CTU.  Describe how the different components of the CTU will communicate and interface with (i) the LOC, LC, and SDMC; (ii) NIAID and other key groups including the DAIDS Office of Clinical Site Oversight (OCSO), the DAIDS Clinical Laboratory Oversight Team (DCLOT), the DAIDS Enterprise System (DAIDS-ES); (iii) the NIAID monitoring contractor; and (iv) the HIV/AIDS Network Coordination (HANC).

Component 5. Evaluation (Limited to 6 pages)

Describe (i) the process including metrics and frequency for assessing operational performance and capacity of all components of the CTU and reporting relevant information to the NIAID and the clinical research network; (ii) how improvements in performance will be achieved; (iii) the process for assessing and evaluating potential PS sites; (iv) how CRSs will be prepared for protocol implementation including responsible parties; and (v) close-out procedures for poorly performing CTU components.

Component 6. Community (Limited to 12 pages)

Describe (i) plans for community engagement including organizational charts; (ii) the role of CAB(s) and how the CAB(s) will support all CRS(s) and their populations(s); (iii) existing relationships between the CRS and community(ies) in which the research will be conducted; include information on nature and length of relationship as well as any outreach conducted to date; (iv) dedicated staff from the CRS, if any, that will support community activities and a description of their roles and responsibilities; (v) CAB composition including process for elections, jurisdiction, representation, function, work products, resource requirements; (vi) the plans for training CAB members including mentoring and continuing education; and (vii) communication with the CTU Administrative Office and the CRS; and (viii) the process for determining the level of financial support that will be provided by the CTU for CAB activities and how that level of support will be reassessed throughout the project period.

Component 7. Pharmacy (Limited to 12 pages)

Organizational Structure. Describe (i) the overall pharmacy structure including a detailed description of lines of authority; specify which (if any) activities are centralized; a diagram showing the roles and relationships of each pharmacy is recommended and should reflect how the pharmacist(s) (or equivalent) will be integrated into CTU organization and management; (ii) the duties and responsibilities of essential pharmacy personnel; include a short summary of the experience, expertise and certification, if applicable, and (iii) describe the level of effort of essential pharmacy personnel (the level of effort must be commensurate with the size and scope of the CTU). 

Facilities and Equipment.  Describe (i) the pharmacy facilities including location, infrastructure, equipment (e.g. refrigerators, freezers, temperature monitoring system, power generator(s)), other specialized equipment, storage, systems for security, inventory or other key processes; (ii) and identify which CRSs the pharmacy facilities will support; (iii) any specialized capabilities available in the pharmacy locations(s); and (iv) the approach for optimizing efficiencies to support proposed clinical research networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches.

Pharmacy Quality Management.  Describe (i) the requirements and processes for developing and implementing pharmacy Standard Operating Procedures (SOPs); the approach for managing pharmacy activities including study product receipt, storage,  preparation, labeling, dispensing, final disposition, record keeping and accountability; participant counseling activities, if applicable; and (ii) how these processes support applicable laws and regulations.

Performance and Experience.  Describe past pharmacy performance and experience over the previous 5 to 7 years with U.S. FDA regulated research as well as non-U.S. FDA regulated research and identify areas for improvement, if any.  Describe the approach for optimizing efficiencies to support proposed networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches.  List any applicable pharmacy certifications and/or accreditations.

Component 8. Laboratory (Limited to 12 pages)

Organizational structure. Describe (i) the plan for CTU staff oversight of laboratory operations and communications, including staff roles and experience; (ii) the overall laboratory structure including a detailed description of lines of authority and identification of which CRSs the laboratory facilities will support; a diagram showing the roles and relationships of each laboratory is recommended; (iii) the duties and responsibilities of essential laboratory personnel; include a short summary of the experience, expertise and certification, if applicable; (iv) the plan for interactions with the clinical research network Laboratory Center (LC); and (v) the level of effort of essential laboratory personnel (the level of effort must be commensurate with the size and scope of the CTU). 

Testing, Equipment and Facilities.  Describe (i) the laboratory testing capabilities, including specialized tests; (ii) the approach for specimen management including receipt, processing, storage, testing, reporting results, tracking, and shipping; (iii) the laboratory facilities including location, infrastructure, equipment (e.g. refrigerators, freezers, temperature monitoring system, power generator(s)), other specialized equipment, storage, systems for security, inventory or other key processes; (iv) identify which CRS(s) the laboratory facilities will support; and (v) the approach for optimizing efficiencies to support proposed clinical research networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches.

Laboratory Quality Management.  Describe (i) the requirements and processes for developing and implementing laboratory SOPs; (ii) how these processes support applicable laws and regulations; and (iii) challenges and solutions for getting materials (e.g. test kits) into the country and specimens out of the country (if applicable).  Include any laboratory certification, quality assurance or other applicable accreditation.

Performance and Experience.  Describe past laboratory performance and experience over the previous 5 to 7 years with U.S. FDA regulated research as well as non-U.S. FDA regulated research and identify areas for improvement, if any.  Describe the approach for optimizing efficiencies to support proposed networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches. 

Component 9. Other Clinical Research Activities (Limited to 12 pages)

Regulatory Assurance.  Describe regulatory requirements for protocol approval and implementation.  Include details of (i) national, central, or local IRB and other regulatory requirements; (ii) past experience and average timeline for protocol approval; (iii) challenges and other unique issues that may have impacted protocol approval and implementation; and (iv) strategies to overcome regulatory hurdles, if applicable.

Describe the plan for ensuring compliance with GCP, local, national, and other applicable regulatory requirements.  Include any unique requirements, issues, previous experience, challenges, and a plan to efficiently collaborate with local IRB or ethics boards to facilitate protocol development and approval. 

Data Management.  Describe (i) the overall data management structure including a detailed description of lines of authority, and specify which (if any) activities are centralized; (ii) the duties and responsibilities of essential data management personnel including assurance of data quality; (iii) the plan for effective interactions between the SDMC and local data management facility; (iv) level of effort of all essential data management personnel (the level of effort must be commensurate with the size and scope of the CTU); (v) the current information technology (IT) infrastructure; and (vi) a plan for ensuring data integrity and security including processes to monitor and restrict access, and data back-up systems.

Quality Management.  Describe (i) the overall quality management plan and structure for all parts of the CTU including a detailed description of lines of authority; specify which (if any) activities are centralized; (ii) the duties and responsibilities of essential quality management personnel; (iii) the level of effort of all essential quality management personnel (the level of effort must be commensurate with the size and scope of the CTU); and (iv) a plan to perform ongoing day-to-day quality checks as well as retrospective, objective, systematic, and periodic reviews of trial-related activities to ensure compliance with protocols, GCP, and NIAID requirements.  Include the process, metrics, frequency of evaluation and documentation of findings, and how modifications to quality management will be determined and implemented.

Staff Training.  Describe (i) how training needs (other than protocol-specific training) will be assessed for all components of the CTU; (ii) how training content will be developed/decided; (iii) how training needs will be reviewed, evaluated, and modified; and (iv) plans for mentoring new staff and providing continuing education for existing staff.

Bylaws, policies, and standard operating procedures should not be included in the application.

Component 10. Clinical Research Site(s) (CRS) (Limited to 12 pages per CRS)

Label each individual CRS (up to 8) with the number and a letter (10A, 10B, 10C, etc.) using the following outline as guidance:

Organizational Structure.  Describe (i) the overall CRS structure including a detailed description of lines of authority; a diagram showing the roles and lines of authority within each CRS is recommended , reflecting support commensurate with the size and scope of the CRS; and; and (ii) the duties and responsibilities of CRS Leader and other CRS personnel.  The CRS leader is considered ‘key personnel’, so a summary of their qualifications, experience and level of effort should be provided on PHS 398 Form Page 2; however the application may expand on the CRS Leader’s scientific and leadership expertise as well as clinical research experience.

Proposed Research Area(s).  (i) Specify proposed NIAID HIV/AIDS clinical research network(s) for each CRS; (ii) identify and expand on potential trial participants (e.g., demographics, incidence and prevalence of HIV/AIDS) to justify proposed network(s) selection; and (iii) describe existing and proposed community engagement plans.

Facilities and Equipment.  Describe (i) the clinic facilities including location, layout, infrastructure, equipment, vehicles, storage, and security and backup systems or other key processes required for efficient, uninterrupted clinical research; and (ii) any specialized capabilities available in the location(s).  It is not necessary to include items described in other components.

Administration.  Describe (i) how activities will be coordinated across multiple clinical research networks, if applicable; (ii) innovative approaches for optimizing efficiencies to support proposed clinical research network(s); and (iii) the approach for ensuring that protocol activities are conducted in accordance with NIAID and all applicable regulatory requirements.

Performance and Experience.  Describe past performance and experience as a CRS or equivalent over the previous 5 to 7 years, including, but not limited to, types of studies conducted, enrollment and retention, data quality metrics, and timeliness of protocol implementation and execution.  Describe challenges and any improvement plans (if applicable). 

A CTU proposing affiliation with the Clinical Research Network on Antibacterial Resistance should NOT list relevant CRS(s) as a separate component in this section of the application.

Component 11. Clinical Research Network on Antibacterial Resistance (Optional Component - Limited to 6 pages)

Applicants proposing participation with the Antibacterial Resistance network should submit a brief capability statement describing capacity and capability to perform clinical trials in antibacterial resistance.  Include evidence of: (i) ability to recruit and retain relevant patient populations, including intensive care unit (ICU) and emergency room patients; (ii) ability to identify, recruit, and manage appropriate sites for antibacterial resistance clinical research or trials; (iii) ability to monitor progress toward enrollment goals and adjust as needed, depending on changing circumstances; and (iv) ability to support local laboratory activities and pharmacy functions.  Applicants are encouraged to draw upon their past experiences with participation in antibacterial resistance, multicenter clinical trials or equivalent experience.

Response to this optional component will not affect the overall impact/priority score for the application.

Letters of Support

Provide a letter signed by the appropriate institutional official(s) from the grantee institution documenting specifics of institutional commitment for this proposed award period.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modification:

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign Institutions

Foreign (non-US) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Although it is not required, applicants may attend one of three planned workshops on preparing an application in response to this FOA. Registration and additional information about these workshops can be found at:  http://www.niaid.nih.gov/labsandresources/restructuring/pages/default.aspx.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete 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-10-115

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 - Overall

Reviewers will provide an overall impact/priority 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).

Is the application reflective of a cohesive and integrated unit, and is the integration evident within each of the components and across the entire CTU?

Considering the overall goals, plans, and approaches outlined in the CTU Research Overview in Component 1, in conjunction with the specific information in Components 2-10, are the proposed size (including number of CRSs), composition and structure of the CTU well justified and adequate to address the scientific areas of the proposed clinical research network(s)?

Are there strong and meritorious organizational, management, and communication plans within the CTU?

Is the application reflective of approaches for efficient utilization of resources and infrastructure, avoidance of redundancies, and cost containment measures? 

Does the application reflect a strong, robust culture of quality management throughout all parts of the CTU?

Overall Impact – CTU Research Overview (Component 1)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the CTU to exert a strong sustained coordinated support of the NIAID HIV/AIDS Networks and the scientific research agendas, in consideration of the following review criteria.

Scored Review Criteria - Component 1

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

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

Does the application describe a cohesive structure and range of support services to accommodate the scientific agenda for the proposed NIAID HIV/AIDS network leadership groups?

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the PD(s)/PI(s), collaborators, and other researchers have appropriate scientific knowledge and research experience to contribute to the development of the clinical research network plans for which they propose to affiliate?

Do the PD(s)/PI(s) have adequate qualifications, experience, level of commitment, and availability to lead and coordinate the CTU and its component parts?

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?

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is there a cohesive, integrated plan across the CTU that addresses integration of functions within each of the scientific areas proposed?

Do the CTU structure, management and governance allow for rapid reconfiguration and access to resources in order to accommodate changes to the scientific agenda for the proposed NIAID HIV/AIDS clinical research network(s)?

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?

Review Criteria– Components 2-10

Reviewers will evaluate the strengths and weaknesses of the scientific and technical merits of application Components 2-10 according to the following review criteria. However, separate scores will not be provided for Components 2-10.  Reviewers will consider the scientific and technical merits of Components 2-10 in the development of an Overall Impact/Priority Score for the application.

For CTU Administration (Component 2), reviewers will consider:

Are the organizational structure, management plan and lines of authority clear and appropriate with respect to the size and scope of the CTU?

Do the key personnel have adequate qualifications, experience, level of commitment, and availability to support and conduct CTU activities?

Does the PD(s)/PI(s) have adequate organizational and management experience to lead the proposed CTU?

Are there innovative approaches for the efficient utilization and sharing of resources, and/or other cost containment measures that support the proposed CTU configuration?

Is there sufficient institutional support for the CTU in terms of space, position(s), administrative assistance, and other resources that support CTU operations?

For Financial Resource Management (Component 3), reviewers will consider:

Is the financial management structure, including the duties, responsibilities, experience, and time commitment of essential staff adequate, with respect to the size and scope of the CTU? 

In order to accomplish CTU goals, are appropriate fiscal management plans and processes proposed to establish consortia agreements, to allocate resources/protocol funds in a transparent manner, and to provide financial reports to NIAID and the LOCs?

Are the criteria used to assess CRS capability to receive protocol funds directly from the Network LOC appropriate? 

For Communication (Component 4), reviewers will consider:

Are there appropriate and feasible plans for effective communication between the CTU and clinical research networks, NIAID and other key groups?

Are there adequate plans for effective communication across all components of the CTU, especially the performance sites?

For Evaluation (Component 5), reviewers will consider:

Does the applicant propose appropriate and feasible procedures to measure and assess the performance, productivity and capacity of the CRSs?

Is there an adequate process for assessing and preparing sites (including PS site(s), if appropriate) for protocol implementation?

Are the plans to improve inadequate performance of CTU component parts both appropriate and feasible?

For Community (Component 6), reviewers will consider:

Is there an existing partnership, or are there adequate, appropriately documented plans for developing such a partnership with the community, to effectively engage the community including the Community Advisory Board(s) in site activities?

Does the proposed CAB structure adequately represent the communities from which the research will be conducted?

Is the plan for training CAB members adequate?

Are the proposed CAB processes adequate and efficient?

Is there evidence that CTU personnel have the ability to interact with the community in linguistic and culturally appropriate ways?

Is the plan for funding CAB activities adequate and transparent?

For Pharmacy (Component 7), reviewers will consider:

Do the essential pharmacy personnel at each identified pharmacy have adequate qualifications (pharmacy education, training and experience) and level of commitment to perform the day-to-day study product management activities?

Are there acceptable facilities (including location, infrastructure, equipment and adequate space) for study product management that will ensure the integrity of the study products required for the range of activities of the proposed NIAID HIV/AIDS clinical research networks?

Does the pharmacy have appropriate policies and procedures for study product management in accordance with applicable regulations or a system in place to develop and implement them?

Are there strong and appropriate plans for pharmacy QA/QC and for training and mentoring of new pharmacy staff?

In support of the proposed pharmacy configuration, are there innovative plans to share and efficiently use resources, and to contain costs?

Is there evidence demonstrating strong past pharmacy performance and experience?

For Laboratory (Component 8), reviewers will consider:

Is the plan for ensuring quality local laboratory operations and effective interactions with local laboratories and the LC adequate?

Do the essential laboratory personnel at each identified laboratory facility have adequate training, qualifications, experience, level of commitment, and availability?

Do the proposed laboratory services demonstrate scientific and technical suitability, appropriateness and feasibility, especially with respect to testing capabilities, facilities, staff, standard operating procedures, plans for laboratory data management, and specimen management?

Are there appropriate measures for laboratory QA/QC, participation in external quality assurance programs, adherence to GCLP and adherence to regulatory agency guidelines?

Are the plans for maximizing organization efficiency and effectiveness adequate and do they include sharing of laboratory resources, harmonization of laboratory activities, and cost containment procedures?

Is there evidence demonstrating strong past laboratory performance and experience?

For Other Clinical Research Activities (Component 9), reviewers will consider:

Is the process for submitting protocols and timeline for approvals through the proposed regulatory infrastructure (e.g.; IRB or Ethics Committees) reasonable and adequate to support the breadth of activities across all parts of the CTU?

Are innovative approaches to addressing any regulatory challenges described?

Is there an adequate plan for ensuring regulatory compliance across all parts of the CTU?

Are the infrastructure and plan for performing data management activities adequate to ensure the accuracy and integrity of the data? 

Is the plan for quality management appropriate given the size and scope of the CTU?

Is the plan for interactions between the SDMC and local data management staff adequate?

Are there well described and adequate plans for staff training and mentoring across all CTU components to support and conduct CTU activities?

For Each Clinical Research Site (Component 10), reviewers will consider:

With respect to the size and scope of the CRS, are the organizational structure, management plan and lines of authority appropriate and clear to ensure effective leadership and oversight of the CRS activities?

With respect to the size and scope of the CRS, does the organizational structure reflect adequate leadership and management experience, level of commitment, and availability of proposed staff?

Does the CRS Leader have adequate leadership and management experience to manage the proposed CRS?

Are there adequate staff with appropriate qualifications and experience to recruit, screen, enroll, follow, retain, and provide the required clinical care?

Based on demographic characteristics and the incidence and prevalence of HIV/AIDS, is there strong documentation for the availability and the appropriateness of the potential participant cohorts to address the research agenda of each proposed clinical research network?

Are there strong plans for, and a documented ability to recruit and retain research participants drawn from population(s) required for the proposed clinical research?

Are there adequate, available, and appropriate facilities to recruit, screen, enroll, follow, retain and provide the clinical care required for the proposed research areas?

Is there evidence of innovative approaches to sharing and efficient utilization of resources, or other innovative cost containment measures that support the proposed CRS?

Is there evidence demonstrating strong past CRS (or equivalent) performance and experience?

For the Optional Clinical Research Network on Antibacterial Resistance (Component 11), reviewers will consider:

The capacity and capability of the CTU to perform clinical trials on antibacterial resistance will not receive a technical merit score.  However reviewers will evaluate the strengths and weaknesses of the scientific and technical merit of optional Component 11 according to the following points.  This evaluation of optional Component 11 will not be factored into the Overall Impact score for the CTU application.

Is there evidence of the ability to recruit and retain appropriate subjects for antibacterial resistance clinical research or trials?

Is there evidence of the ability to identify, recruit, and manage appropriate CRS for antibacterial resistance clinical research or trials?

Is there evidence of experience monitoring progress toward enrollment goals and ability to adjust the number of clinical sites (increase or decrease)?

Is there evidence of laboratory and pharmacy experience in antibacterial resistance testing, e.g., minimum inhibitory concentration (MIC)?

Response to this optional component will not affect the overall impact/priority score for the application.

Additional Review Criteria - Overall

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

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

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

Revisions

Not Applicable. 

Additional Review Considerations - Overall

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/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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) Genome Wide Association Studies (GWAS).

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 NIAID in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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 and 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 Allergy and Infectious Diseases Council l. The following will be considered in making funding decisions:

The NIAID reserves the right to conduct site visits or reverse site visits prior to award when deemed essential.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons

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

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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

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.

Responsive applications will serve as Clinical Trials Units focused on the following clinical research networks:

CTU PD(s)/PI(s) will have primary responsibility for the overall activities and performance of the CTU, including, but not limited to:

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

Program Official: Staff assistance will be provided by a NIAID Program Officer.  These NIAID staff members will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond the normal program stewardship role for grants:

These staff will be identified at the time of award and their roles and responsibilities will be addressed in the NOA.

NIAID will serve as a liaison between pharmaceutical companies, the FDA, and clinical research network(s) investigator(s) and/or partners.  In accordance with NIH policy, NIAID will ensure that all clinical trials performed through the CTU are conducted in accordance with ICH GCP and applicable Federal regulations.

Areas of Joint Responsibility:

Execution of this program will require collaboration among the CTU PD(s)/PI(s), the NIAID staff, the Network LG and other co-sponsoring NIH Institutes and Centers. Specific tasks and responsibilities in carrying out the activity will be shared among the awardee, NIAID staff, Network staff, and NIAID contractors as described above.

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 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 awardees. 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 Non-Competing Continuation Grant Progress Report (PHS 2590) 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.

WEB SITE INFO:  http://www.niaid.nih.gov/labsandresources/restructuring/pages/default.aspx

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Bola Adedeji, R.Ph., M.S.
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Room 5111, MSC-7624
6700B Rockledge Drive
Bethesda, MD 20892-7624
express mail: Bethesda, MD 20817
Telephone:  301-496-7122
FAX: 301-480-7675
e-mail: badeniran@mail.nih.gov 

Peer Review Contact(s)

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (for Express Mail – 20817)
Telephone: 301-496-8426
FAX: 301-480-2310     
Email: pjackson@niaid.nih.gov

Financial/Grants Management Contact(s)

Ann Devine
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 2114, MSC 7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone 301-402-5601
FAX: 301-493-0597
Email: adevine@niaid.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 Parts 74 and 92.


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