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)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Mental Health (NIMH)

Funding Opportunity Title

Leadership Group for a Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations (UM1) 

Activity Code

UM1 Multi-Component Research Project Cooperative Agreements

Announcement Type

Reissue of RFA-AI-05-001

Related Notices

  • June 29, 2012 - See Notice NOT-AI-12-036. The purpose of this Notice is to inform the extramural research community of the replacement of instructions for the following Sections: Section IV. Application and Submission Information, Part C. Instructions Specific for the Statistical and Data Management Center (SDMC) Application; and Section V. Application Review Information, Part C. Statistical and Data Management Center (SDMC) Review Criteria.
  • June 20, 2012 - Clarification on NIH HIV/AIDS Clinical Network Responsibilities for the Use of Antibody-based Therapies for the Prevention and Treatment of HIV Infection. See Notice NOT-AI-12-035.
  • April 10, 2012 - See issuance of RFA-AI-12-018, Clinical Trials Units for NIAID Networks (UM1).

Funding Opportunity Announcement (FOA) Number

RFA-AI-12-001

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.855, 93.856; 93.242; 93.865; 93.121 

FOA Purpose

The purpose of this FOA is to solicit applications for the Leadership Group for a Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations.  The Leadership Group (LG) will have overall responsibility for developing, implementing and adapting the network’s clinical research agenda to address NIAID’s HIV/AIDS scientific priorities described below (Part 2, Section I, #3). Applications for the LG must be comprised of three separate linked UM1 applications: a Leadership and Operations Center (LOC), a Laboratory Center (LC) and a Statistical and Data Management Center (SDMC).

Key Dates
Posted Date

January 27, 2012

Letter of Intent Due Date

August 28, 2012

Application Due Date(s)

September 28, 2012   

AIDS Application Due Date(s)

Not Applicable. 

Scientific Merit Review

March, 2013     

Advisory Council Review

October, 2013 

Earliest Start Date(s)

December, 2013  

Expiration Date

September 29, 2012 

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 encourage applications for the Leadership Group (LG) for a Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations.  The LG will have overall responsibility for: (i) developing, implementing and adapting the network’s clinical research agenda to address NIAID’s HIV/AIDS scientific priorities described below in Part 2, Section I, 3, (ii) overseeing and managing the network’s scientific/clinical research activities and associated laboratory and statistical/data management support functions, (iii) allocating network resources, and (iv) evaluating network performance using a LG proposed/Division of AIDS (DAIDS) approved process and evaluation standards. 

The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) and senior/key personnel of the LOC, LC and SDMC together form the LG. The LG coupled with the Program Directors/Principal Investigators (PDs/PIs) and senior/key personnel of the affiliated Clinical Trial Units/Clinical Research Sites (CTUs/CRSs) collectively constitute the Clinical Research Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations (herein referred to as the “network”). The three different parts of the LG, LOC, LC and SDMC will be required to work together collaboratively and with the network-affiliated CTUs/CRSs to carry out the activities that are essential to achieving the network’s clinical research agenda.

Clinical Trial Units (CTUs) provide the scientific and administrative expertise as well as the infrastructure to contribute to NIAID Clinical Research Networks.  A CTU is an organization/institution composed of at least one, but no more than eight CRSs that can contribute to at least twoHIV/AIDS Clinical Research Networks.  The CTU PD(s)/PI(s) is/are responsible for all CTU/CRS activities and performance, and also serve(s) as scientific and administrative representative(s) to the CTU’s affiliated network(s).

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 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.

2.  Background

NIAID currently supports six HIV/AIDS clinical research networks: the AIDS Clinical Trials Group (ACTG), the HIV Prevention Trials Network (HPTN), the HIV Vaccine Trials Network (HVTN), the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), and the Microbicide Trials Network (MTN).

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), 33 million people globally are estimated to be living with HIV, of whom 22 million 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.

Among the most significant advances in the field of HIV treatment has been the ability to prevent mother-to-child transmission (MTCT), which is now less than 2 percent in high-income countries.  Even in low-income countries, the use of antiretroviral (ARV) drugs during pregnancy, intrapartum, and after birth including during breast feeding, has reduced MTCT substantially.  UNAIDS estimates that over 340,000 infections in infants are averted each year; nevertheless, over 370,000 infants still become HIV-infected.

Although access to care and treatment services for HIV-infected children in low-income countries is expanding, an estimated 260,000 children died from HIV/AIDS in 2007, adding to more than 4 million children already claimed by the epidemic.  Without treatment, approximately one-half of children who are HIV-infected will die by their second birthday.

The known timing of infection makes infants an important population to study. The timing of intrapartum infant infection can be pinpointed to within a few days, allowing unique research into HIV reservoirs and interventions to prevent their development. The presence of a functional thymus in infants may offer the best opportunity to evaluate immunomodulatory changes that may lead to a functional cure.

Treatment of infants, children, adolescents and pregnant women with HIV or HIV-associated infections presents unique challenges.  Palatable powder or liquid formulations for infants and children can be difficult to manufacture; approximately half of the current oral antiretroviral agents are not available in a pediatric formulation and even fewer have indications or dosing recommendations for infants or young children.  In addition, concerns about teratogenicity prevent or delay clinical trials of many needed medications for pregnant women. The use of biomedical and behavioral interventions to prevent HIV infection cannot be adopted in adolescents until feasibility and acceptability are established in that age group.

The high mortality rate in children with HIV is due in part to their susceptibility to the many childhood infections endemic to geographic areas with high HIV prevalence.  Children are at risk for death due to tuberculosis (TB), or other respiratory and gastrointestinal illnesses.  Some of these illnesses can be prevented or at least ameliorated by vaccines; however, often vaccines are not available or it is unknown whether HIV-infected children should receive the standard vaccination or use an augmented schedule.  In addition, it is unclear if vaccinating HIV-infected pregnant women affects their susceptibility to infection and/or protection for their infants.

Questions still remain about the impact of HIV infection and/or long-term antiretroviral therapy on the growing and developing child. Untreated HIV infection has deleterious effects on growth and development; however, it is unclear how effectively early antiretroviral treatment can ameliorate non-infectious complications of HIV.  While early treatment reduces morbidity and mortality from HIV, treatment is not without consequences.  The total impact of antiretroviral drug exposure perinatally, throughout childhood and during puberty is not known.

In recognition of the frequent occurrence of HIV related oral diseases, both in treated and untreated HIV infected individuals, the NIAID in collaboration with the National Institute of Dental and Craniofacial Research (NIDCR) seeks for the inclusion and implementation of an oral health research agenda, in which clinical interventions are linked to, and integrated within, the HIV/AIDS research priority areas. 

3.  Research Priority Areas

The network will focus its research on infants, children, adolescents and pregnant/postpartum women with HIV or HIV-associated infections, or, in some cases, at high risk for HIV infection.  NIAID’s scientific priority areas to be addressed by the LG of the network in their proposed clinical research agenda include the following (not listed in priority order):

Examples of research within these priority areas include, but are not limited to the following:

Vaccines of high priority:

Cure and/or functional cure of HIV: utilizing the unique opportunity presented by the known timing of intrapartum transmission to:

Co-infections, co-morbidities and consequences of antiretroviral therapy:

Strategies to prevent acquisition of HIV:

Pharmacology, drug formulations and novel interventions:

In relation to the HIV related oral disease research agenda special emphasis will be put on addressing: 1) oral immune activation (IRIS), oral inflammation and oral immune dysregulation; 2) oral mucosal lesions including oral fungal-, HIV- and viral-opportunistic infections as well as eradication of these infections from oral mucosal reservoirs; 3) viral-related tumors and malignancies of the oral cavity

4.  Application Requirements

The LG will be responsible for all network activities and will ensure that all the constituent parts of the network fulfill their respective responsibilities in the most efficient and effective manner possible.  Each part of the LG linked application (LOC, LC, and SDMC) is expected to demonstrate scientific leadership, effective management and efficient utilization of resources.

Leadership Time Commitment.  When a single PD/PI is proposed in any of the three LG applications, the PD/PI will be required to devote at least 6 person months effort to the project.  Applications proposing Multiple PD(s)/PI(s) are permitted, but the roles and responsibilities of multiple PD(s)/PI(s) should be clearly delineated and justified.  If two or more PD(s)/PI(s) are named in any application, each PD/PI must devote at least 3.6 person months effort to the project.

The governance and organizational structure of the LG leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD(s)/PI(s) and other collaborators.

Research Agenda.  The LG’s clinical research agenda should be clearly articulated and directly related to achieving NIAID’s scientific priorities.  The LG is required to monitor and evaluate the need to refine and revise the research agenda. As part of this process, the LG is required to actively engage input from researchers and HIV-affected communities.

Governance and Management.  The LOC, LC and SDMC, in their areas of responsibility, must establish and define effective communication and decision making processes, identify clear lines of authority, coordinate and collaborate effectively both within the network and with other NIH-supported networks or other Federal and private sector clinical research programs as appropriate to avoid redundancies and ensure efficiencies.  Governance or management by committees is permitted.  The governance and management should utilize effective approaches to project management, including project plans with identified key milestones; ongoing evaluation of projections against actual data and adjustments to project plans; and development and implementation of contingency plans. In addition, the LOC, LC and SDMC, in their area of responsibility, must establish processes to identify and resolve operational issues and develop training and education programs within the context of the network’s research agenda for network members, including new researchers, particularly from under-represented populations and those in low and middle income countries.

Bylaws, policies and standard operating procedures should not be included in the application, but must be provided, for approval, to NIAID within 90 days of Notice of Award.

Resource Utilization and Allocation.  The LOC, LC and SDMC, in their area of responsibility, must ensure optimal resource utilization and ensure that resource allocation supports the clinical research agenda.

Collaborative Responsibilities. The LG will be strongly encouraged to collaborate with other NIH-supported networks and other Federal and private sector clinical research programs, and to interact with government and non-government organizations, including the private sector, and committees to effectively develop and implement a clinically relevant, interdisciplinary and cost-efficient clinical research network.  Such collaborations and interactions are essential for the development and implementation of a comprehensive research agenda that utilizes the strengths, experience and expertise of the various collaborating organizations.  The sharing of expertise, resources and procedures is expected in key areas, including: development of clinical infrastructure in low-income countries; harmonization of laboratory resources and specimen management; harmonization of common data elements and data entry interfaces; community engagement, including development, training and support of community advisory boards. Examples of additional entities the LG will need to collaborate and/or communicate with include, but are not limited to:  the Adolescent Medicine Trials Network (ATN), the NIAID Strategic Working Group (SWG), Scientific Review Committees (SRCs),  network LG Program Officers (NLGPOs) and Project Scientists, the Division of AIDS (DAIDS) Enterprise System (DAIDS-ES), Office of Clinical Site Oversight (OCSO), the DAIDS Clinical Laboratory Oversight Team (DCLOT), the HIV/AIDS Network Coordination Office (HANC), other HIV/AIDS Clinical Research Network groups and the non-HIV/AIDS Research Network.

5. Leadership and Operations Center, Laboratory Center and Statistical and Data Management Center Specific Responsibilities 

In addition to the requirements described above, each LG segment has the following specific responsibilities:

Leadership and Operations Center (LOC)

The LOC provides overall scientific and administrative leadership for the network and coordination of the LG with the network-affiliated CTUs/CRSs.  The PD(s)/PI(s) of the LOC thus have primary responsibility for the network.  The LOC is responsible for: (i) overseeing research concept prioritization, protocol development and implementation, completion of final study reports, and timely publication and communication of results; (ii) developing and implementing network governance and resource management policies and procedures; (iii) fostering and ensuring engagement and effective partnership with affected communities in strategic planning; (iv) evaluating and revising the network’s research agenda; (v) overseeing and evaluating the performance of each LG segment and network-affiliated CTUs/CRSs; and, (vi) allocating network resources (as described below in Section I.6. Protocol Funds and Distribution). 

Laboratory Center (LC)

The LC contributes to the development of the network’s research agenda, and leads the laboratory activities that are required to carry out the research agenda.  The LC is responsible for (i) managing, monitoring and evaluating all LG-supported laboratory services, any network specimen repositories, and laboratory quality management programs and (ii) fostering collaboration and harmonization of laboratory activities within the network, at network-affiliated CTUs/CRSs laboratories, and with other NIH-supported networks or other Federal and private sector clinical trial programs engaged in similar research.

Statistical and Data Management Center (SDMC)

The SDMC assists with the development of the network’s clinical research agenda and provides biostatistical leadership in study design, analysis, interpretation and publication of results, along with state-of-the-art clinical and laboratory data management systems to ensure complete, high quality data.  The SDMC is responsible for: (i) ensuring the integrity of study design, data management, data analyses and compliance with regulatory requirements, as appropriate; (ii) providing effective data communication systems for the network; (iii) providing data management training for network-affiliated CTUs/CRSs investigators and laboratory staff; (iv) standardizing and harmonizing statistical and data management activities both within the network and with other NIH-supported networks or other Federal and private sector clinical trial programs when required; and, (vi) collecting and storing data in accordance with standards of the Clinical Data Interchange Standards Consortium (C-DISC) requirements.

6.  Core and Protocol Funds

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

Core Funds (Grant Awards)

Protocol Funds (PF)

A more expansive definition of Core and PF can be found at the web site listed in Section VII of this FOA.

NIAID expects that equipment and services funded via Core or PF will be made available, as appropriate, for other NIAID funded network activities regardless of how funds were initially provided to purchase those items.

Distribution of Protocol Funds to Network-Affiliated CTUs/CRSs

When it is determined that network-affiliated CTUs/CRSs need protocol funds, in addition to CTU/CRS Core Funds to carry out the network’s research agenda, there are two routes for disbursement of these protocol funds. The PD(s)/PI(s) of the LOC are required to state in their application which of the two following routes they choose for disbursement of protocol funds to network-affiliated CTUs/CRSs:

Route 1

Route 2

Regardless which route is chosen, the LOC will be required annually to determine protocol milestones and estimate the amount of PF that will be required to meet these milestones and provide this information to NIAID. Following discussions between NIAID and the LOC, NIAID will determine the amount of PF to be provided to the network in the coming grant year. If the network chooses Route 2 above for PF distribution, budgets received from CTUs must be shared with, and approved by NIAID prior to disbursement to CTUs/CRSs.  Changes in PF allocation will be made during the award period if key milestones are not met. Whether funds may be routed directly from the LOC to a network-affiliated CRS will be determined after the CTU competition is complete. No matter the arrangement of PF distribution, the CTUs will have the primary responsibility for PF accounting.

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 and partner components intend to commit up to an estimated total of $20 million of Core funding in FY14 to fund 1 award each for the LOC, LC, SDMC comprising the Leadership Group for a Clinical Research Network on HIV/AIDS and HIV- associated Infections in Pediatric and Maternal Populations.

Award Budget

Total costs are limited to $20M for FY 14 to be disbursed, as Core funding,  among the three awards constituting the LG  .

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

Common Fund/Roadmap text, Collaborative Research, or Projects Greater than 5 years Duration:  See instructional documents in the NIH Guide Publishing System for the text to insert.

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 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 four (4) 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.

When a single PD/PI is proposed in any of the three LG applications, the PD/PI will be required to devote at least 6 person months effort to the project.  If two or more PD(s)/PI(s) are named in any application, each PD/PI must devote at least 3.6 person months effort to the project.    

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.

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 LG applicants are asked to submit a letter of intent for each application that identifies the other linked applications being submitted for the LG. Each letter must be signed by the PD(s)/PI(s) for the corresponding application, LOC, LC, or SDMC. Each letter should include the following information:

The letter of intent should be sent to:

Peter R. Jackson, PhD
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
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, PhD
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
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 

Applicants responding to this FOA must submit three separate linked applications: (1) a Leadership and Operations Center (LOC) application, (2) a Laboratory Center (LC) application, and (3) a Statistical and Data Management Center (SDMC) application.  These three separate linked applications can be a combination of new or renewal applications.  A separate Cover Letter must be included with each of the three linked applications, including: a listing of all the applications that are a part of the set of linked UM1s being submitted, including for each: 1) the PD(s)/PI(s) name(s), 2) the Title (tagging each application LOC 1/3, LC 2/3, and SDMC 3/3), and 3) the Applicant Institution.  Each of the three applications must be submitted as a separate package. Submissions that do not contain the required three linked applications will be considered nonresponsive to this FOA and will not be reviewed.  Each of the three applications, if successful, will receive a separate grant award.

All three separate linked applications must be submitted separately, including a separate Cover Letter listing all the applications that are a part of the set of linked UM1s being submitted.  The three separate linked applications include:

Each of the above listed applications must have a common base title, provided by the applicant, item #1 on the PHS 398 Form.  The title of each application should begin with a tag denoting which part of the LG (i.e., Leadership and Operations Center, Laboratory Center or Statistical and Data Management Center) is represented in that application.  Titles may not exceed 81 characters including the base title and tag. Abbreviations of LOC, LC and SDMC may be used in the title.

Cover Letter

A separate cover letter is required for each of the three linked applications.  In addition to the Cover Letter instructions in Part I, Section 3.1 of the PHS 398 Grant Application instructions, each separate Cover Letter must include: a listing of all the applications that are a part of the set of linked UM1s being submitted, including for each: 1) the names of the PD(s)/PI(s), 2) the Title (tagging each application LOC 1/3, LC 2/3, and SDMC 3/3), and 3) the Applicant Institution.  Each of the three applications must be submitted as a separate package

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 Applications

The following section provides supplemental instructions to the PHS398 Grant Application instructions for the preparation of linked multi-component applications (UM1). This section is divided into three subsections, with specific and detailed instructions for the linked applications, LOC, LC and SDMC.  NOTE:  To be responsive to this FOA, applicants must submit three separate linked UM1 applications consisting of the LOC, LC and SDMC.  Each of these three linked applications must be submitted as a separate package with a separate cover letter  tagged with: LOC (1/3), LC (2/3), and the SDMC (3/3).  . Each application must have a common base title plus a tag at the beginning of the project that denotes the linked application (e.g., Leadership and Operations Center or the abbreviation LOC may be used).  Titles need to be succinct so that they do not exceed 81 characters.  A separate cover letter must be included with each application package and contain a listing of the three linked applications, the PD/PIs, the titles (including the tag) and the applicant institution(s). The information included in the cover letter must also be an attachment in each application.

Applicants should follow the instructions in the PHS398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html), incorporating the following deviations from the PHS398 instructions noted under the specific headings below for each of the three separate, linked multi-component UM1 applications.   

NOTE:  The Leadership Group Overview must be included as Component 1 within each of the three linked applications and the content of the Leadership Group Overview must be identical in each.

A. Instructions Specific for the Leadership and Operations Center (LOC) Application

Use the table of contents below as a supplemental guide to the PHS 398 instructions to assemble the multi-component LOC application. 

ITEM

Application 1: Leadership and Operations Center (LOC)

Copy of Application Package Cover Letter

Face Page – LOC (Form Page 1). This is the first page of the LOC application; number all succeeding pages consecutively.

Description, Project/Performance Sites, Senior Key Personnel and Key Personnel, Other Significant Contributors, Human Embryonic Stem Cell statement if applicable(Form Page 2). Make sure the abstract describes how the proposed components will contribute to the LOC objectives.

Detailed Budget for First Year (use PHS 398 Form Page 4).

Proposed budgets should be for CORE cost only,  not to include any protocol cost (PF)

Composite Budget for All Years of Proposed Period of Support (use PHS 398 Form Page 5 and continuation pages of Form Page 5)

A separate page of Detailed Budgets for Consortium Agreements to be summed as a line item on page 4

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

Resources (Resources Format Page).  Complete the resources available for each component

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. 

LOC, LC and SDMC Component 1.  Leadership Group Overview

LOC Component 2:  Research Agenda/Strategies

LOC Component 3:  Protocol Development and Implementation

LOC Component 4:  Structure and Governance

LOC Component 5:  Resource Management and Protocol Funds

LOC Component 6:  Research Capacity

LOC Component 7:  Evaluation, Improvement and Training/

LOC Component 8:  Communications and Collaborations

Resource Sharing Plan

Appendix

Checklist – LOC (Checklist Form Page)


Component 1: Leadership Group Overview

Component 1 will be identical for all three linked applications and must be included in the LC and SDMC applications

Specific Aims (Limited to 1 page): List the scientific aims of the Leadership Group (the combined scientific aims of the LOC, LC and SDMC).

Research Overview for Component 1 (Limited to 30 pages)

Provide a brief history and background of the field of clinical research overall, including a discussion of knowledge gaps and future opportunities, and briefly summarize the proposed scope of research for the LG.

Describe in detail (i) the overall clinical research agenda of the proposed LG; (ii) the significance of each priority area as outlined in the Research Priority Areas (Part 2 Section I, #3); and (iii) how the scientific agenda will help improve the treatment and/or prevention of HIV/AIDS, especially in populations disproportionately impacted by HIV/AIDS. Summarize (i) the proposed approach(s) to making high level scientific and management decisions for the LG; (ii) research prioritization, reassessment, redirection, and involvement of key stakeholders and external expertise; and (iii) how decisions will be linked to cost effective management of network resources.

Briefly summarize the structure and organization of the three linked applications for the LG. Include (i) a description of the proposed approach to integrating the functions of the linked applications and plans for coordinating with the network-affiliated CTUs/CRSs and CRS-affiliated laboratories (ii) an organizational chart(s) showing senior/key personnel with level of effort for leadership or decision-making positions in the LOC, LC and SDMC, and briefly describe how they will relate to each other and to the network-affiliated CTUs/CRSs; (iii) a description of the roles and responsibilities of the PD(s)/PI(s) of each application,  or multiple PDs/PIs if proposed, and the experience of each in leading and managing a complex clinical trials program; and (iv) plans to ensure adequate representation of early career investigators, investigators of both genders, and investigators representative of populations disproportionately affected by HIV/AIDS.

Performance and Applicant Experience.  For renewal applications, (i) expand upon   accomplishments of the LG during the current award period, including key contributions to the field and scientific strengths; (ii) identify areas for improvement; (iii) describe collaborations established and implemented with other NIAID- and NIH-sponsored clinical trial networks and/or other clinical researchers/research programs and the value of these collaborations to the field; and (iv) describe any innovative scientific or administrative approaches undertaken during the current award.  For new applications, provide the information identified above pertinent to the PI’s/PD’s expertise during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

Additional Instructions and Page Limits for the Specific Aims and Research Strategy Section of Each Individual Component of the LOC Application

LOC Component 2.  Research Agenda/Strategies

Specific Aims (Limited to 1 page): List and describe the scientific aims of the LOC

Research Strategy (Limited to 30 pages)

Organize this section in the order specified in the PHS 398 Instructions Section 5.5.  Make sure to start each section with the appropriate section heading in order, addressing Significance, Innovation, and Approach, and including the appropriate information.  Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

Experience.  Describe the relevant experience of the LOC in directing, overseeing and managing a clinical trials leadership and operations group. 

Research Agenda.  Provide a focused research agenda for each of the five scientific priority areas stated in Part 2, Section I.3. above.  Identify agenda areas of highest priority and the significance and anticipated contributions to the field during the period of award.  Include (i) specific strategies or approaches; (ii)  process and procedures for developing milestones and timelines for completing key studies; and (iii) preliminary data/documentation of the feasibility of the proposed approaches.

Prioritization of Research Agenda.

Performance and Applicant Experience. Within the Approach section, for renewal applications, (i) expand upon past performance of the LOC; (ii) identify strengths and areas for improvement; and (iii) provide improvement plans.  For new applications, provide the information identified above pertinent to the PI’s/PD’s expertise during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

LOC Component 3.  Protocol Development and Implementation (Limited to 12 pages)

(i) Explain how performance will be managed using standard principles of project management, including processes and procedures to ensure that protocols are developed, initiated, completed and results disseminated on schedule. (ii) Define roles and responsibilities of staff for Component 3 and how the LOC will achieve synergism between the LOC, LC and SDMC.  Do not name staff or investigators here (see Component 4 below). (iii) Describe the approach to developing approved research concepts into protocols, including go/no-go criteria, contingency plans, decision and communication processes, and plans for ensuring adherence to NIAID/DAIDS and network policies and procedures. (iv) Describe the approach to protocol implementation and completion, including: critical protocol implementation milestones/timelines; plans for modifying protocol implementation milestones/timelines. (v) Describe the processes and timelines for completing final study reports and publication. In addition, describe the process for fast tracking both the development and implementation of high priority protocols and managing the impact on other protocols.  

LOC Component 4.  Structure and Governance (Limited to 12 pages)

Describe in detail the plans for network governance and LOC management and structure.  Tables, diagrams, flow charts and organizational charts are strongly recommended.   Describe how the LOC will be governed, including: (i) lines of authority; (ii) decision making processes; (iii) any proposed governance/decision making committees and their authorities; (iv) senior/key personnel (level of effort, experience/qualifications) involved in network-wide governance  and/or committees; and (v) process for setting network meeting: agendas, frequency, participants and location.

Bylaws, policies and standard operating procedures should not be included in the application, but must be provided for approval to NIAID within 90 days of issuance of the Notice of Award.

LOC Component 5.  Resource Management and Protocol Funds (Limited to 12 pages)

Route Selection and Justification.  Applicants must select one of the two routes for the distribution of Protocol Funds to the network-affiliated CTUs/CRSs.  A mixture of routes will not be permitted.  Select one of the routes described in Section I.6 (i.e., Route 1 or Route 2) and provide a justification for the route selected.   If no route is selected NIAID will utilize Route 1.

Roles and Responsibilities.  Provide a structure for and describe the financial management of network resources, including: lines of authority; decision making and management processes; and senior/key personnel including their levels of commitment, specific financial management roles and responsibilities, training, experience and qualifications. 

Policies and Procedures.  Describe the procedures for determining and calculating the amount of protocol implementation funds to be requested for the LOC, LC, SDMC and network-affiliated CTUs/CRSs to achieve the network’s research agenda.  Include any formulas or templates to be used.

LOC Component 6.  Research Capacity (Limited to 12 pages)

Needs.  (i) Describe the research capacity characteristics required to accomplish the network’s research agenda; include capacity needs, and the nature of the populations to be recruited.  (ii) Indicate how these needs may change/shift over the award period. (iii) Describe the current process(es) for assessing  CTU/CRS capacity, and for identifying the need for additional research capacity that cannot be met through the existing structure (i.e. CTU/CRS infrastructure in place post new CTU awards in FY14), which could include expansion of CTUs or the addition of protocol specific sites or external venues such as randomized communities.  (iv) Describe how the LOC will ensure that these processes remain transparent to the network affiliated CTUs.  Do not name specific CTUs/CRSs in the application.

Interactions. Describe (i) plans and decision process for CRS selection, including a transparent process for reviewing, selecting and developing additional research capacity that cannot be met through the existing research infrastructure; (ii) procedures and timelines for CRS protocol activation including milestones, responsible persons, and how activation will be synchronized with protocol development and approval; (iii) how protocol- specific training will be developed and efficiently delivered;  (iv) plans and decision process for reducing research capacity including site closure if necessary; and (v) how investigators in low and middle income settings will be supported in their engagement and education of local Institutional Review Boards (IRB)/Ethics Committees (EC) and regulatory review committees to facilitate protocol review and approval.  

LOC Component 7.  Evaluation, Improvement and Training (Limited to 12 pages)

Describe how (i) performance of the LOC, LC, SDMC and network-affiliated CTUs/CRSs will be evaluated; (ii) CRSs will be prepared for protocol implementation including responsible parties; and (iii) training needs for network members will be determined, provided, and evaluated, and how necessary changes in training programs/approaches will be decided and implemented.

LOC Component 8.  Communications and Collaborations (Limited to 12 pages)

Provide proposed LOC communication and collaboration plans, including the roles and responsibilities of involved individuals.

Community.   Describe plans for community engagement, including organizational charts and a written description of the role and nature of community input, from individuals and from groups, in all aspects of the network.  Do not name specific community based organizations (CBOs) and non-government organizations (NGO) community advisors or organizations.  Do provide the names, expertise/experience, roles and responsibilities of paid LOC staff who will be involved in community activities. 

Cross-network and Other Research Collaborations.  Describe plans and procedures for determining network roles and responsibilities in collaborations with other NIH-supported clinical research networks or other potential collaborators, including the processes for negotiating and overseeing joint activities, sharing resources, and resolving disputes. Provide plans for participation in cross-network coordinating bodies, especially with HANC.  Do not name investigators who are outside of the Network in the application.

NIH Interactions.   Provide a plan delineating how NIAID’s network LG Program Officer and other NIH staff responsible for facilitating the work conducted by the networks will be integrated into network activities.  Also identify and describe the expertise, experience and qualifications of the LG’s proposed representative on the NIAID SWG and alternates, when required.

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, with the following modifications:

B. Instructions Specific for the Laboratory Center (LC) Application

Use the table of contents below as a supplemental guide to the PHS 398 instructions to assemble the multi-component LC application.

ITEM    

Application 2: Laboratory Center (LC)

Copy of Application Package Cover Letter

Face Page – LC (PHS 398 Form, Page 1). This is the first page of the LC application; number all succeeding pages consecutively.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cell statement if applicable (PHS 398 Form, Page 2).  Make sure the abstract describes how the proposed components will contribute to the LC objectives.

Detailed Budget for First Year (use PHS 398 Form, pages 4)

Proposed budgets should be for CORE cost only,  not to include any protocol cost (PF)

Composite Budget for All Years of Proposed Period of Support (use PHS 398 Form Page 5 and continuation pages of Form Page 5)

A separate page of Detailed Budgets for Consortium Agreements to be summed as a line item on page 4

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

Resources (Resources Format Page).  Complete the resources available for each component.

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. 

LOC, LC and SDMC Component 1.  Leadership Group Overview

LC Component 2:  Research Strategy and Methodologies

LC Component 3:  Structure and Governance

LC Component 4:  Quality Management, Evaluation and Improvements

LC Component 5:  Research Capacity

LC Component 6:  Communications and Collaborations

Biohazards

Resource Sharing Plan

Appendix

Checklist – LC (Checklist Form Page).


Component 1: Leadership Group Overview

Component 1 will be identical for all three linked applications and must be included in the LOC and SDMC applications.

Specific Aims (Limited to 1 page): List the scientific aims of the Leadership Group (the combined scientific aims of the LOC, LC and SDMC).

Research Overview for Component 1 (Limited to 30 pages)

Provide a brief history and background of the field of clinical research overall, including a discussion of knowledge gaps and future opportunities, and briefly summarize the proposed scope of research for the LG.

Describe in detail (i) the overall clinical research agenda of the proposed LG; (ii) the significance of each priority area as outlined in the Research Priority Areas (Part 2 Section I, #3); and (iii) how the scientific agenda will help improve the treatment and/or prevention of HIV/AIDS, especially in populations disproportionately impacted by HIV/AIDS. Summarize (i) the proposed approach(s) to making high level scientific and management decisions for the LG; (ii) research prioritization, reassessment, redirection, and involvement of key stakeholders and external expertise; and (iii) how decisions will be linked to cost effective management of network resources.

Briefly summarize the structure and organization of the three linked applications for the LG. Include (i) a description of the proposed approach to integrating the functions of the linked applications and plans for coordinating with the network-affiliated CTUs/CRSs and CRS-affiliated laboratories; (ii) an organizational chart(s) showing senior/key personnel with level of effort for leadership or decision-making positions in the LOC, LC and SDMC, and briefly describe how they will relate to each other and to the network-affiliated CTUs/CRSs; (iii) a description of the roles and responsibilities of the PD(s)/PI(s) of each application,  or multiple PD(s)/PI(s) if proposed, and the experience of each in leading and managing a complex clinical trials program; and (iv) plans to ensure adequate representation of early career investigators, investigators of both genders, and investigators representative of populations disproportionately affected by HIV/AIDS.

Performance and Applicant Experience.  For renewal applications, (i) expand upon   accomplishments of the LG during the current award period, including key contributions to the field and scientific strengths; (ii) identify areas for improvement; (iii) describe collaborations established and implemented with other NIAID- and NIH-sponsored clinical trial networks and/or other clinical researchers/research programs and the value of these collaborations to the field; and (iv) describe any innovative scientific or administrative approaches undertaken during the current award.  For new applications, provide the information identified above pertinent to the PI’s/PD’s expertise during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

Additional Instructions and Page Limits for the Specific Aims and Research Strategy Section of Each Individual Component of the LC Application

LC Component 2.  Research Strategy and Methodologies

Specific Aims (Limited to 1 page): List and describe the scientific aims of the LC

Research Strategy (Limited to 30 pages)

Organize this section in the specified order stated in the PHS 398 Instructions Section 5.5.  Make sure to start each section with the appropriate section heading in order, addressing Significance, Innovation, and Approach, including the appropriate information.  Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

 Research Approach. Discuss the LC’s research strategy, its significance and expected contributions to the field, emphasizing how this strategy supports and integrates with the research agenda and synergizes with other parts of the LG and CTUs/CRSs to achieve network goals.

Performance and Applicant Experience. Within the Approach section,  for renewal applications, (i) expand upon the accomplishments of the LC during the current award period, including key contributions to the field; (ii) identify areas for improvement; (iii) describe collaborations established and implemented with other NIAID- and NIH-supported clinical trial networks and/or other clinical researcher/research programs, and the value of these collaborations to the field and any innovative scientific approaches and (iv) document the utility and effectiveness of any repositories supported by the LC.  For new applications, provide the information identified above pertinent to the expertise of the PD(s)/PI(s) during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

LC Component 3.  Structure and Governance (Limited to 12 pages)

 Describe in detail the proposed organizational structure of the LC and plans for governance.

Organizational Structure.  (i) Describe the overall LC structure, identifying the number, types, roles and significance of each laboratory and repository, if any.  A diagram showing the roles and relationships of each laboratory and repository is recommended.   (ii) Provide a LC staffing plan and organizational chart, identifying senior/key personnel and providing descriptions of duties and responsibilities, a short summary of relevant training, experience and expertise, and time commitment.  (iii) Describe the process for establishing LC committees, including the structure and roles of each proposed committee and the procedures for establishing new committees and disbanding those that are no longer needed.  Do not include names of committee members other than those supported by the LOC, LC and SDMC.

Governance.  (i) Describe the decision making process for responding to changes in testing needs and capacity, and the management approach for establishing and ensuring adherence to timelines and maintaining cost efficiency.  (ii) Describe the requirements and processes for developing and implementing laboratory SOPs; the approach for specimen handling, acquisition, processing, shipping, tracking, testing, storage and retrieval; the laboratory data management system (LDMS) to be used and involved personnel, and how specimen repositories will be managed.  (iii) Discuss requirements for protocol-specific laboratory documents and processes for document development and implementation.  Do not include the names of potential advisors.  Rather provide areas of expertise, nature and frequency of potential consultations/meetings, etc. 

Bylaws, policies and standard operating procedures should not be included in the application, but must be provided to NIAID within 90 days of issuance of the Notice of Award for approval.

LC Component 4.  Quality Management, Evaluation and Improvements (Limited to 6 pages)

Describe (i) how all aspects of the LC will be evaluated and improved, including the process, metrics and frequency for evaluating the entire LC effort and resolving problems/deficiencies;  (ii) laboratory quality management procedures, including requirements for external quality assurance (EQA), validations, reference range studies and laboratory audits; and (iii) the processes for determining the need for and development and implementation of  alternative EQA, and how the LC will interact with DAIDS quality assurance contracts.  Do not include names of external advisors other than those supported by the LOC, LC and SDMC. 

LC Component 5.  Research Capacity (Limited to 6 pages)

Describe the procedures and interactions among laboratories and other parts of the network for performing routine, non-specialized testing, collecting and processing specimens when necessary, and shipping to one or more laboratories within and outside the LC for specialized testing or to a repository.  Additionally, describe and discuss CTU/CRS data input methodology, how assay capacity assessment and training will be accomplished, how CTU/CRS affiliated laboratories will be evaluated, and problem resolution processes and procedures.  Describe procedures and requirements to minimize redundancies for training staff at CTU/CRS-affiliated laboratories associated with multiple networks.

LC Component 6.  Communications and Collaborations (Limited to 6 pages)

 Describe how the LC will establish and maintain clear lines of communication and procedures for collaborating within the network and with other NIH-supported networks, HANC or other Federal or private sector clinical programs to achieve assay harmonization, minimize costs and avoid test redundancies.  Discuss the ability, capacity and willingness of the LC to perform testing and provide training on specific assays for laboratory personnel for other NIH-supported clinical trial networks.

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, with the following modifications:

C. Instructions Specific for the Statistical and Data Management Center (SDMC) Application

Use the table of contents below as a supplemental guide to the PHS 398 instructions to assemble the multi-component SDMC application. 

ITEM

Application 3: Statistical and Data Management Center (SDMC)

Copy of Application Package Cover Letter

Face Page – SDMC (PHS 398 Form, Page 1).  This is the first page of the SDMC application; number all succeeding pages consecutively.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cell statement if applicable(Form Page 2).  Make sure the abstract describes how the proposed components will contribute to the SDMC objectives.

Detailed Budget for First Year (use PHS 398 Form Pages 4)

Proposed budgets should be for CORE cost only,  not to include any protocol cost (PF)

Composite Budget for All Years of Proposed Period of Support (use PHS 398 Form Page 5 and continuation pages of Form Page 5)

A separate page of Detailed Budgets for Consortium Agreements to be summed as a line item on page 4

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

Resources (Resources Format Page).  Complete the resources available for each component.

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

LOC, LC and SDMC Component 1.  Leadership Group Overview

SDMC Component 2:   Methodologies and Technical Capabilities

SDMC Component 3:  Structure and Governance

SDMC Component 4:  Research Capacity

SDMC Component 5: Communications and Collaborations

Resource Sharing Plan

Appendix

Checklist


Component 1:  Leadership Group Overview

Component 1 will be identical for all three linked applications and must be included in the LOC and LC applications.

Specific Aims (Limited to 1 page): List the scientific aims of the Leadership Group (the combined scientific aims of the LOC, LC and SDMC).

Research Overview for Component 1 (Limited to 30 pages)

Provide a brief history and background of the field of clinical research overall, including a discussion of knowledge gaps and future opportunities, and briefly summarize the proposed scope of research for the LG.

Describe in detail (i) the overall clinical research agenda of the proposed LG; (ii) the significance of each priority area as outlined in the Research Priority Areas (Part 2 Section I, #3); and (iii) how the scientific agenda will help improve the treatment and/or prevention of HIV/AIDS, especially in populations disproportionately impacted by HIV/AIDS. Summarize (i) the proposed approach(s) to making high level scientific and management decisions for the LG; (ii) research prioritization, reassessment, redirection, and involvement of key stakeholders and external expertise; and (iii) how decisions will be linked to cost effective management of network resources.

Briefly summarize the structure and organization of the three linked applications for the LG. Include (i) a description of the proposed approach to integrating the functions of the linked applications and plans for coordinating with the network-affiliated CTUs/CRSs and CRS-affiliated laboratories; (ii) an organizational chart(s) showing senior/key personnel with level of effort for leadership or decision-making positions in the LOC, LC and SDMC, and briefly describe how they will relate to each other and to the network-affiliated CTUs/CRSs; (iii) a description of the roles and responsibilities of the PD/PI of each application,  or multiple PDs/PIs if proposed, and the experience of each in leading and managing a complex clinical trials program; and (iv) plans to ensure adequate representation of early career investigators, investigators of both genders, and investigators representative of populations disproportionately affected by HIV/AIDS.

Performance and Applicant Experience.  For renewal applications, (i) expand upon   accomplishments of the LG during the current award period, including key contributions to the field and scientific strengths; (ii) identify areas for improvement; (iii) describe collaborations established and implemented with other NIAID- and NIH-sponsored clinical trial networks and/or other clinical researchers/research programs and the value of these collaborations to the field; and (iv) describe any innovative scientific or administrative approaches undertaken during the current award.  For new applications, provide the information identified above pertinent to the PI’s/PD’s expertise during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

Additional Instructions and Page Limits for the Specific Aims and Research Strategy Section of Each Individual Component of the SDMC Application

SDMC Component 2.  Methodologies and Technical Capabilities

Specific Aims (Limited to 1 page): List and describe the scientific aims of the SDMC

Strategy (Limited to 30 pages).

Organize this section in the specified order stated in the PHS 398 Instructions Section 5.5.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

Research Approach.  Describe (i) the roles and responsibilities of SDMC staff in providing general support for network activities, including, but not limited to:  protocol design and development, data analysis, preparation of data summaries (within and across protocols), and publication of results; (ii) development of data collection systems, forms and formats, and generic and protocol-specific instruments (paper and/or electronic) and (iii) how statistical methodologies and/or database systems and structures will be adapted to accommodate the Network’s needs and with other NIH-supported networks or other Federal, or Non Government Organization (NGO), or private sector clinical programs when required.

Data Management Plans and Systems. 

Performance and Applicant Experience. Within the Approach section, for renewal applications, (i) expand upon the accomplishment of the SDMC during the current award period, including key contributions to the field; (ii) identify areas for improvement; (iii) describe collaborations established and implemented with other NIAID- and NIH-supported clinical trial networks and/or other clinical researcher/research programs, the value of these collaborations to the field and any innovative scientific approaches; and (iv) describe experience in developing and validating data systems to support controlled clinical trials.  For new applications, provide the information identified above pertinent to the PI’s/PD’s expertise during the past 5 years leading a clinical trials program of similar scope and complexity in this area of research.

SDMC Component 3.  Structure and Governance (Limited to 12 pages)

Describe in detail the proposed organizational structure of the SDMC and plans for governance.

Organizational Structure.  (i) Describe the overall SDMC structure, including detailed description of the lines of authority;  (ii) Provide a SDMC staffing plan and organizational chart, identifying senior/ key personnel and providing descriptions of duties and responsibilities, a short summary of relevant training, experience and expertise, and time commitment; (iii) Describe how the SDMC staff will interface in a synergistic manner within the SDMC and the other parts of the network; and (iv) Describe the process for establishing SDMC committees, including the structure and roles of each proposed committee and the procedures for establishing new committees and disbanding those that are no longer needed.

Statistical Staff.  Describe the organization of the statistical staff and the duties, responsibilities, experience, expertise and time commitment of key staff.  Identify those staff with responsibility for contributing to the identification and resolution of statistical issues and those staff with data analysis responsibilities.

Data Management Staff.  Describe the organization of the data management staff and the duties, responsibilities, experience, expertise and time commitment of key staff.  Identify those staff with responsibility for contributing to data management decisions and functions, and describe the roles and activities involved in the development and maintenance of data systems including expertise in data security and in CDISC.

Management and Governance.   Describe (i) how the SDMC will be managed and governed, including the requirements and processes for development and implementation of SDMC SOPs; (ii) how personnel assignments will be made; (iii) the decision-making process for assessment and adaptation of new data management or statistical methods, procedures, designs or tools; (iv) how decisions will be made for setting and adhering to timelines and the consequences of failure to meet established timelines; (v) methods for establishing and maintaining cost efficiency and (vi) procedures for proposing committees, including their structures and roles, and  the process for assessing the need for new committees, selecting committee members, and dissolving committees.  Do not include names of committee members outside the LOC, LC and SDMC.

Bylaws, policies and standard operating procedures should not be included in the application, but must be provided to NIAID within 90 days of issuance of the Notice of Award for approval.

SDMC Component 4.  Research Capacity (Limited to 12 pages)

 Describe (i) the procedures and interactions between the SDMC, other parts of the network LG, and CTUs/CRSs for data collection and transmission to the SDMC, and for data collection from the LC when laboratory data are generated; (ii) procedures and methodologies to be used to assess the capabilities and readiness of network-affiliated CTUs/CRSs including new protocol specific CRSs for data collection, processing, analysis (if appropriate) and transmission; (iii) the requirements and procedures for the overall evaluation of data collection, transmission and management processes within the SDMC and between the SDMC and the network-affiliated CTUs/CRSs and (iv) how SDMC training needs for network members will be determined and provided, how the training will be evaluated and how necessary changes in training will be decided and implemented.

SDMC Component 5.  Communications and Collaborations (Limited to 6 pages)

 Provide a plan for efficient SDMC communication within the network and with other NIH-supported networks or other Federal and private sector clinical programs and NIH staff, including methods for SDMC communication with the DAIDS-ES to automate data transfer and resolve any data transfer issues/problems that arise, including those affecting data integrity and timeliness of submission.

Data and Safety Monitoring Boards (DSMBs).   Describe how the SDMC will interact with DSMBs.  Provide SDMC policies and procedures, including staff roles and responsibilities in the timely provision of confidential closed and/or open data sets.

Inter-Network Collaborations.  (i) Discuss approaches for working cooperatively with other NIAID and non-NIAID-funded networks and HANC to harmonize data collection processes across networks, and develop and implement standard data interfaces, commonly defined variables, and common data elements.  (ii) Identify methods for minimizing costs and avoiding redundancies.  (iii) Discuss the capacity and willingness of the SDMC to assist other clinical trial networks and to provide training to SDMC personnel from other networks, if needed.

Other Interactions.  Describe the SDMC’s role and approach for soliciting input from, and communicating with external organizations such as corporate sponsors and the FDA, including sharing of data sets with outside sponsors seeking INDs/Investigational Device Exemptions (IDEs)/New Drug Applications (NDAs)/ Biologics License Agreements (BLAs)/Pre-Market Approvals (PMAs) for the purpose of submitting clinical/final study reports.  Also discuss procedures for soliciting input and consulting and communicating with investigators outside the network.

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 modifications:

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, with the following modifications:

 Each linked application will have its own appendix.

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.

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.

A. LEADERSHIP AND OPERATIONS CENTER (LOC) REVIEW CRITERIA

OVERALL IMPACT – OVERALL LOC

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the LOC, to exert a strong sustained influence on the research field involved, in consideration of the following review criteria (as applicable for the LG proposed).

Review Criteria

Considering the overall goals, plans, and approaches outlined in the Leadership Group Overview in Component 1, in conjunction with the specific information in Components 2-8, is the LOC application cohesive? Is there evidence of synergistic interactions among the Components that enhance the likelihood of LOC success?"

Overall Impact-Overview (Component 1)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the LOC, as presented in the Overview, to exert a strong sustained influence on the research field involved, in consideration of the following review criteria and additional review criteria (as applicable for the LOC proposed).

Review Criteria

Is the proposed clinical research agenda meritorious, innovative, feasible and sufficiently flexible to address future scientific opportunities? Are the 1st year plans timely and appropriate?  Does the application depict an ability to adjust to future requirements and activities?  Does the proposed research plan have potential for applicability to the groups most disproportionately impacted by HIV/AIDS, including women, adolescents, and racial/ethnic minorities? Are there adequate plans to obtain input from representatives of highly impacted communities at every stage of research development? Where appropriate, are there adequate and feasible plans to ensure the involvement of new and early career investigators, foster the participation of women and racial/ethnic minorities as researchers, and ensure their participation in network activities at all levels? Do the proposed PDs/PIs have adequate scientific and organizational qualifications, time commitment, experience and vision for the concept, coordination, and direction of the network and the LOC? If multiple PDs/PIs are proposed, does their expertise match their roles and are individual responsibilities clearly delineated?  

Overall Impact –Research Agenda/Strategies (LOC Component 2)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the successful implementation of the research agenda/strategies 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 LOC proposed).

Scored Review Criteria –Research Agenda/Strategies (LOC Component 2)

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 research agenda address an important problem or a critical barrier to progress in the field? If the aims of the network 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?   

For each of the five scientific priority areas stated in Part 2, Section I-3, does the proposed research agenda have the potential to significantly advance HIV treatment, prevention and clinical care?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to pursue the research agenda? If Early Stage Investigators or New Investigators, or are 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 LOC 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 to implement the research agenda for the LOC?

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 network? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of development, will the LOC’s strategy establish feasibility and will particularly risky aspects be managed? 

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?   

Are the proposed network processes to assess, evaluate and redirect the scientific priorities as the field evolves sound and feasible?

Where appropriate are there adequate plans to solicit external and internal input and assessments of the research agenda and for prioritizing research concepts? Do the plans include adequate processes for the integration of novel ideas and expertise from inside and outside the network and the field?

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 research agenda proposed? Will the implementation of the research agenda benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

Additional Review Criteria – LOC Components 3-8

Reviewers will consider each of the criteria but will not give separate scores for these items below in the determination of scientific merit and will give an overall score for each Component 3-8.

For Protocol Development and Implementation (Leadership Component 3) the reviewers will consider:

For Structure and Governance (LOC Component 4) the reviewers will consider:

For Research Management and Protocol Funds (LOC Component 5) the reviewers will consider:

For Research Capacity (LOC Component 6) the reviewers will consider:

For Evaluation, Improvement and Training (LOC Component 7) the reviewers will consider:

For Communication and Collaborations (LOC Component 8) reviewers will consider:

Additional Review Criteria - Overall LOC

As applicable for the LG 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 Network 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 LOC

As applicable for the LG 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

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) 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.

B.  LABORATORY CENTER (LC) REVIEW CRITERIA

OVERALL IMPACT – OVERALL LC

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the LC to exert a strong sustained influence on the research field involved, in consideration of the following review criteria (as applicable for the LG proposed).

Review Criteria

Considering the overall goals, plans, and approaches outlined in the Leadership Group Overview in Component 1, in conjunction with the specific information in Components 2-6, is the LC application cohesive? Is there evidence of synergistic interactions among the Components that enhance the likelihood of LC success?"

Overall Impact-Overview (Component 1)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the LC, as presented in the Overview, to exert a strong sustained influence on the research field involved, in consideration of the following review criteria and additional review criteria (as applicable for the LC proposed).

Review Criteria

Are the proposed laboratory activities meritorious, innovative, feasible and sufficiently flexible to address the Research Agenda of the proposed Network? Does the LC application depict an ability to adjust to future scientific opportunities, requirements and activities? Does the proposed research plan have potential for applicability to the groups most disproportionately impacted by HIV/AIDS, including women, adolescents, and racial/ethnic minorities? Are there adequate plans to obtain input from representatives of highly impacted communities at every stage of research development? Do the proposed PD(s)/PI(s) have adequate scientific and organizational qualifications, time commitment, experience and vision for the concept, coordination, and direction of the network and the LC? If multiple PD(s)/PI(s) are proposed, does their expertise match their roles and are individual responsibilities clearly delineated?  

Overall Impact - Research Strategy and Methodologies (LC Component 2)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the successful implementation of the research strategy and methodologies 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 LC proposed).

Scored Review Criteria - Research Strategy and Methodologies (LC Component 2)

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

Do the research strategy and methodologies address an important problem or a critical barrier to progress in the field? If the aims of the LC 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?   

Are the proposed laboratory research aims and strategies meritorious, innovative, feasible and sufficiently flexible for addressing the network’s clinical research agenda? Do the proposed laboratory research activities have the potential to advance HIV treatment, prevention and clinical care?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to implement the research strategy and employ methodologies of the LC? 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 LC 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 research strategy and methodologies of the LC?   

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 network? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of development, will the LC’s research strategy establish feasibility and will particularly risky aspects be managed?

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?   

Do the proposed process for determining the need for new assays or methodology, and the plan for development, assessment and implementation of  new laboratory assays and technologies have appropriate scientific and technical merit?

Is there a clear plan for the integration within the network and will this plan lead to synergism?  

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 investigators adequate for the research strategy and methodologies proposed? Will the implementation of the research strategy and methodologies benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Are the proposed number, type and location of laboratories and network specimen repositories adequate and appropriate to meet network research plans?

Additional Review Criteria – LC Components 3-6

Reviewers will consider each of the criteria but will not give separate scores for these items below in the determination of scientific merit and will give an overall score for each Component 3-6.

For Structure and Governance  (LC Component 3) reviewers will consider:

For Quality Management, Evaluation and Improvements (LC Component 4) reviewers will consider:

For Research Capacity (LC Component 5) reviewers will consider:

For Communications and Collaboration (LC Component 6) reviewers will consider:

Additional Review Criteria - Overall LC

As applicable for the LC 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 Network 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 LC

As applicable for the LC 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

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) 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.

C.  STATISTICAL AND DATA MANAGEMENT CENTER (SDMC) REVIEW CRITERIA

OVERALL IMPACT – OVERALL SDMC

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the SDMC to exert a strong sustained influence on the research field involved, in consideration of the following review criteria (as applicable for the LG proposed).

Review Criteria

Considering the overall goals, plans, and approaches outlined in the Leadership Group Overview in Component 1, in conjunction with the specific information in Components 2-5, is the SDMC application cohesive? Is there evidence of synergistic interactions among the Components that enhance the likelihood of SDMC success?

Overall Impact-Overview (Component 1)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the SDMC, as presented in the Overview, to exert a strong sustained influence on the research field involved, in consideration of the following review criteria and additional review criteria (as applicable for the SDMC proposed).

Review Criteria

Is the proposed biostatistical management agenda meritorious, innovative, feasible and sufficiently flexible to address the Network research plans?  Does the SDMC application depict an ability to adjust to future scientific opportunities, requirements and activities? Does the proposed research plan have potential for applicability to the groups most disproportionately impacted by HIV/AIDS, including women, adolescents, and racial/ethnic minorities? Are there adequate plans to obtain input from representatives of highly impacted communities at every stage of research development? Do the proposed PD(s)/PI(s) have adequate scientific and organizational qualifications, time commitment, experience and vision for the concept, coordination, and direction of the network and the SDMC? If multiple PD(s)/PI(s) are proposed, does their expertise match their roles and are individual responsibilities clearly delineated?  

Overall Impact –Methodologies and Technical Capabilities (SDMC Component 2)

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the collective methodologies and technical capabilities of the SDMC to exert a sustained, powerful influence on the research field involved, in consideration of the following review criteria and additional review criteria (as applicable for the proposed SDMC).

Scored Review Criteria - Methodologies and Technical Capabilities (SDMC Component 2)

Reviewers will consider each of the 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

Do the methodologies and technical capabilities enable the SDMC to address an important problem or a critical barrier to progress in the field? If the aims of the SDMC 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?

Is there potential for scientific contributions to the clinical research agenda through SDMC participation in the design, conduct, analysis and publication of clinical research?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the SDMC? 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? If the SDMC 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 SDMC?

Do the proposed PD(s)/PI(s) possess adequate qualifications, level of commitment, experience and availability to provide the scientific and administrative direction of a multi-network clinical trials statistical and data management center?

Is there adequate and appropriate leadership in biostatistics, clinical systems, study design, data analysis, data management, and result interpretation to ensure complete and high quality research data?

If multiple PD(s)/PI(s) are proposed, does their expertise match their roles and are individual responsibilities clearly delineated?

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 network? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of development, will the SDMC’s strategy establish feasibility and will particularly risky aspects be managed? 

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?   

Are there strong, meritorious, appropriate and feasible plans and procedures for providing all data management services required, including database design, security, confidentiality and administration, participant randomization/registration, data collection, quality control, data retrieval, safety data reconciliation between clinical sites and DAERS, report generation and site training?

Are the plans to assure compliance with regulatory requirements for data, including compliance with CDISC, adequate?

Is there a clear plan for integration within the network and will this lead to synergism?  

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 proposed SDMC?  Will the SDMC benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria – SDMC Components 3-5

Reviewers will consider each of the criteria but will not give separate scores for these items below in the determination of scientific merit and will give an overall score for each Component 3-5.

For Structure, and Governance (SDMC Component 3) reviewers will consider:

For Research Capacity (SDMC Component 4 ) reviewers will consider:

For Communication and Collaboration (SDMC Component  5) reviewers will consider:

Additional Review Criteria – Overall SDMC

As applicable for the SDMC 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 Network 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 SDMC

As applicable for the SDMC 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

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) 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 National Institute of Allergy and Infectious Diseases, NIH , 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:

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 appropriate national Advisory Council or Board  . The following will be considered in making funding decisions:

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

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.

PDs/PIs of the Leadership Group (LOC, LC and SDMC) will have primary responsibility for the overall performance of the network, including, but not limited to:

Each leadership group will have the responsibility to collaborate and promote inter-network interactions, including but not limited to:

PDs/PIs of the Leadership and Operations Center (LOC) will have primary responsibility for the scientific leadership, administration and coordination of all network activities and the LOC, including, but not limited to:

PD(s)/PI(s) of the Laboratory Center (LC) will have the primary responsibility for the overall planning, execution and review of all laboratory center activities including, but not limited to:

PD(s)/PI(s) of the Statistical and Data Management Center (SDMC) will have primary responsibility for the biostatistical and data management activities, including, but are not limited to:

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role for these awards, as described below and as applicable to the specific applications:

Program Official and Project Scientist. NIAID staff assistance will be provided by a DAIDS Program Official and Project Scientists along with other NIH staff.  These staff will be identified at the time of award and their roles and responsibilities will be addressed in the Notice of Award (NoA).  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:

Areas of Joint Responsibility between NIH and Awardees include:

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.

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.

Additional information and definitions of terms can be found at the following website. 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)

Judi Miller, BSN
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Room 5227, MSC-7624
6700B Rockledge Drive
Bethesda, MD 20982-7624 (for Express Mail- 20817)
Telephone:  301-496-1189
FAX:  301-480-4582
Email: jmillera@niaid.nih.gov

Lynne M. Mofenson MD
Center for Research for Mothers and Children
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD
Room 4B11E, MSC-7510
6100 Executive Boulevard
Rockville, MD 20852-7510
Telephone:  301-435-6870
FAX:  301-496-8678
Email: LM65D@nih.gov

Dr. Isaac Rodriguez-Chavez
National Institute for Dental and Craniofacial Research (NIDCR)
Director, NIDCR, DER, AIDS & Immunosuppressive Program
Room 614, MSC 4878
6701 Democracy Boulevard
Bethesda, MD 20892-4878
Telephone: 301-594-7985
FAX: 301-402-3684
Email: isaac@nidcr.nih.gov

Dr. Pim Brouwers
Center for Mental Health Research on AIDS
National Institute of Mental Health (NIMH)
Room 6216, MSC-9619
6001 Executive Boulevard
Bethesda, MD  20892-9619
Telephone:  301-443-4526
FAX:  301-443-9719
Email:  ebrouwer@mail.nih.gov

Peer Review Contact(s)

Peter R. Jackson, PhD
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
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)

Tina Carlisle
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2121, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone:  301-402-6579
FAX:  301-493-0597
Email:  tcarlisl@niaid.nih.gov

Bryan Clarke
Office of Administrative Management
Eunice Kennedy Shriver National Institutes of Child Health and Human Development
Room 8A01, MSC-7510
6100 Executive Boulevard
Bethesda, MD  20892-7510
Telephone:  301-435-6975
Email:  clarkb1@mail.nih.gov

Rita Sisco
Division of Extramural Research
National Institute of Mental Health
Room 6120, MSC-9605
6001 Executive Boulevard
Bethesda, MD  20892-9605
Telephone:  301-443-2805
FAX:  301-480-1956
Email:  siscor@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 Parts 74 and 92.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
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