Part I Overview Information

Department of Health and Human Services

Issuing Organization
National Institute of Allergy and Infectious Diseases (NIAID), (http://www3.niaid.nih.gov/ )

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov )

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID), (http://www3.niaid.nih.gov/ )

Title: Tropical Medicine Research Centers (P50)

Announcement Type
This is a reissuance with modifications of RFA-AI-00-009, issued January 24, 2000.

Update: The following update relating to this announcement has been issued:

• October 15, 2010 - This RFA has been reissued as (RFA-AI-11-001).

• The National Institute of Allergy and Infectious Diseases (NIAID) invites applications for Tropical Medicine Research Centers (TMRC). Each Center must be located in a geographic area where at least one of the following diseases is endemic: Leishmaniasis, Chagas Disease, and human African trypanosomiasis. The focus of the application should be on only one of these diseases.
• The total funding available for this program is $2.6 million per year for five years.
• It is anticipated that 3-4 awards will be made.
• The mechanism of support will be the Specialized Center grant (P50). The P50 supports multi-project grants in which all the projects are interrelated to a common goal.
• The TMRC must have at least two interrelated research projects, one of which must be a clinical study. Clinical trials are not allowed. In addition, the TMRC must have an Administrative Core and a Data Management Core.
• Only non-U.S. organizations and institutions located in areas endemic for Leishmaniasis, Chagas Disease, or human African trypanosomiasis are eligible to apply. Applications may be submitted by for-profit and not-for-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories and government agencies in the endemic country.
• The TMRC must be located in a politically stable setting where there are no unusual safety or security threats. The country where the TMRC is being proposed should not have a history of protracted U.S. State Department warnings. See Section III 1.A. Eligible Principal Investigators (PIs) include individuals with the skills, knowledge, and resources necessary to carry out the proposed research and to work with their institution to develop an application for support. The TMRC will be headed by a Program Director who shall commit at least 40% effort to the project and who must serve as Project Leader on one of the research projects.
• An institution may submit only one application in response to this RFA.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Background

Diseases caused by tropical parasites are global health problems that disproportionately affect populations residing in less developed countries. It is estimated that 20 percent of the world's population carries a helminthic parasite infection, and that 10 percent are infected with parasites causing malaria, schistosomiasis, filariasis, leishmaniasis or trypanosomiasis. To address the need for research into fundamental questions about host pathogen interaction, NIAID initiated the TMRC program in 1991. Awards are made on the basis of a competitive peer review process. This program has supported research on a broad range of tropical parasitic diseases in endemic areas. Currently, there are four TMRCs.

This RFA is focused on diseases caused by the parasites of the Trypanosomatidae family: Leishmaniasis, Chagas Disease, and Human African Trypanosomiasis. These diseases remain constant threats to the lives of humans throughout large areas of Africa, Asia, and South America. Depending upon individual strains of the parasites, diseases caused by these organisms can last for weeks to years and can be fatal if left untreated. At present, there are no vaccines against these diseases and treatment options are limited. The treatments that exist are often associated with severe side effects and toxicities. Furthermore, in some instances, parasites have been reported to be resistant to drug treatment. These diseases are a major public health threat for people living in tropical and subtropical regions of the world and are responsible for limiting individual productivity and socioeconomic development. With the recent sequencing of the trypanosomatid genomes, new scientific opportunities are expected to emerge in the areas of diagnostics, therapeutics, vaccine development, immunopathogenesis, immunogenetics, epidemiology, resistance patterns, susceptibility of cohorts, and vector biology, which will lead to or result in new tools or strategies for diagnosis, prevention, amelioration, and/or treatment of diseases caused by the trypanosomes.

Leishmaniasis. Leishmaniasis is transmitted by the bite of the infected phlebotomine sandfly which thrives mostly in warm climates. Leishmaniasis is endemic in 88 countries on five continents with clinical manifestations ranging from disfiguring cutaneous and mucocutaneous lesions that can cause widespread destruction of mucous membranes to visceral disease affecting the liver, spleen and bone marrow. It is estimated that approximately 12 million people are affected worldwide with a total of 350 million people at risk. Over the last decade, it has become apparent that leishmaniasis is becoming a major public health problem both in terms of geographical spread and incidence.

Chagas disease. Chagas disease is endemic in 21 countries throughout the Americas. The geographical distribution of the human Trypanosoma cruzi infection extends from Mexico to the south of Argentina. The disease affects 16 - 18 million people and some 100 million (approximately 25% of the population of Latin America) are at risk for acquiring Chagas disease.

The risk of infection with Chagas disease is much higher in economically disadvantaged populations. The triatomine vector that transmits the parasite is usually found in crevices in the walls and roofs of poor housing. In the past, Chagas disease was primarily a rural problem; with urban migration that occurred in Latin America in the 1970's and 1980's, however, the traditional epidemiological pattern changed, and Chagas disease has now emerged as an urban problem, too, with infection that can be transmitted by blood transfusion. Blood bank surveys conducted in selected cities in endemic areas indicate that the prevalence of infected blood varies between 3.0 and 53.0 %. Thus, in some areas, the prevalence of T. cruzi-infected blood exceeds that for blood infected with HIV, Hepatitis B, and Hepatitis C.

There are two well defined stages of human Chagas disease: the acute stage which appears shortly after the infection, and the chronic stage which appears after a clinically silent period (often termed an indeterminate phase) that may last several years. The lesions of the chronic phase irreversibly affect various internal organs, notably the heart, esophagus and colon. After several years of an asymptomatic period, 27% of those infected develop cardiac manifestations which may lead to sudden death, and 6% develop digestive damage manifest as megaesophagus or megacolon.

Human African Trypanosomiasis (HAT). Human African trypanosomiasis, transmitted by the bite of the tsetse fly, threatens over 60 million people in 36 countries. The early phase of the disease is manifested by irregular fever, lymphadenopathy, headache, myalgia, fatigue, and general malaise. Occasionally a chancre can be seen at the location of the tsetse bite. Pruritus and rash may also be present. The second phase begins when the parasite crosses the blood-brain barrier and infects the central nervous system. If patients do not receive treatment during the first phase, the neurological damage that occurs during the second phase may sometimes be irreversible despite treatment during the second phase. This disease almost disappeared between 1960 and 1965 but has now resurged as vector control, screening, and effective surveillance were relaxed. It is estimated that only 3-4 million people have access to a health center for regular examination and screening for HAT. The drugs used to treat this disease are difficult to administer, have undesirable and severe side effects, and are sometimes ineffective. In addition, the incidence of resistance to some of the available drugs has risen to 30% in some parts of central Africa. The identification, validation and development of new and improved diagnostics, new and improved therapies for both first and second stage disease, as well as a better understanding of the pathogenesis and the role of the blood-brain barrier, and the mechanism(s) of drug resistance, are all critical areas for investigation.

The morbidity and mortality due to these three tropical diseases in endemic areas are increasing due to changing ecological patterns and the incomplete effectiveness of currently available control measures. Emergence of drug resistance and side effects of the available treatments also pose special challenges. Moreover, these diseases are of increasing global concern as tourism, trade, business travel, immigration and military activities extend the range of these infectious agents. For example, migration of people into the U.S. from Chagas disease endemic areas has raised concerns over blood product transmission of Chagas disease within the U.S.

Advances in biomedical technology and the recent success in sequencing the trypanosomatid genomes have opened up exciting possibilities for the development of diagnostics, vaccines, pharmacologic- and immunologic-based therapeutics, and transmission control methodologies. The need for sustained research support in these areas persists, especially support for clinical and field efforts that depend upon access to populations of pathogens, patients and invertebrate vectors and support for translational research that can utilize these genomic advances and lead to concrete examples of new control/intervention tools.

Research Objectives and Scope

The TMRC program will support research requiring access to endemic populations and is limited to Leishmaniasis, Chagas Disease, and human African trypanosomiasis in areas that are endemic for these diseases. Each TMRC will focus on one of these diseases. Relevant research activities for support under this RFA include, but are not limited to, projects involving clinical research, epidemiological and field aspects of Leishmaniasis, Chagas, and HAT, as well as supportive research related to the biology of host-vector-infectious agent interactions. Relevant disciplines include, but are not limited to, genetics, immunology, pathogenesis, pharmacology, development and evaluation of diagnostic tests, clinical science, and medical entomology. A major outcome of this research program is to ensure that TMRCs with demonstrated success with their research projects and infrastructure are capable of positioning themselves to conduct future clinical trials, implement immunotherapeutic, immunoprophylactic, chemotherapeutic and chemoprophylactic methods, and implement vector control strategies that may be deployed as part of national control efforts.

NOTE: This RFA will not support studies of micronutrients, pre-clinical studies, including toxicology and animal studies, and studies that do not require access to endemic sites or populations. In addition, studies focused on the impact of HIV infection on Leishmaniasis, Chagas Disease, and human African trypanosomiasis are supported by other NIAID activities and will not be considered responsive to this solicitation.

This RFA will support clinical studies but not clinical trials. (For clarification of these terms, see http://www.niaid.nih.gov/ncn/glossary/default2.htm .) Clinical trials that will not be supported include: research conducted on patients to evaluate new medical treatments, vaccines, drugs or devices; treatments to compare current or standard treatments with experimental therapies; and studies designed to test the efficacy or effectiveness of an intervention in humans. Small scale, limited trials of innovative potential vector control strategies that assess impact on prevalence or incidence of human disease are allowed. Investigators interested in conducting clinical trials are referred to the NIAID Program Announcements for Clinical Trial Planning Grants (R34) and Clinical Trial Implementation Grants (U01) at http://www.niaid.nih.gov/ncn/clinical/R34.htm .

SPECIAL REQUIREMENTS

1. Program Overview (Overall Research Goals and Objectives and Strategic Plan)

The application must identify and describe the overall goals and objectives of the TMRC, the potential importance of the proposed research to the health and well being of the population in the endemic area, the TMRC organization, the participating institutions, and the role of all consortium members. The application should include a strategic plan for strengthening research capacity at the endemic site and for disseminating research findings to health leaders of the country where the disease is endemic.

The following areas should be included in the Program Overview:

• Strengths - Identify and describe the strengths of the proposed TMRC, including a brief summary of the research and development experience and expertise of the participants, as well as the current facilities and other research resources available. Identify and evaluate the potential opportunities to establish high quality research programs, and the capacity of the TMRC research team to function independently. Discuss how the goals of the TMRC and how the specific projects will enhance clinical research capacity at the TMRC site, e.g., laboratory and/or clinical infrastructure.
• Research Focus - The intent of the TMRC is to support research with the potential to significantly improve the health and well being of individuals living in the endemic countries. Describe how the proposed research will translate in the future into improved diagnostics, disease control, preventive or therapeutic interventions, and/or improved clinical management or public health practice. The application should also state how the research may potentially impact future public health policy.
• Structure Provide a detailed plan for the organizational structure, lines of authority and communications, and staffing of the proposed TMRC. This includes: (1) an organizational diagram showing the various TMRC participating institutions, projects, and proposed staffing for scientific, technical and administrative functions; (2) a narrative description of the roles and responsibilities of all scientific and administrative staff and their level of effort; and (3) a narrative description of plans and procedures for ensuring adequate coordination among participating institutions and personnel, with plans for data sharing, publication agreements and publication goals.

2. TMRC Program Director

Responsibility for leadership of each TMRC rests with the Program Director (PD) who must be a resident of the country of award and must possess demonstrated scientific and administrative competence. The PD should be located at and affiliated with the institution at which the TMRC will reside. The PD is expected to contribute at least 40% effort to the program and exercise leadership in program development and integration, quality control, administration, and scientific collaboration within the program. The PD must have the ability to ensure quality control and the experience to administer both the clinical and non-clinical research effectively and integrate all components of the program. Responsibility for the planning, direction, and execution of the proposed research plans for the TMRC will be solely that of the PD. If desired, a U.S. Co-PD may be designated; however participation of a U.S. Co-PD is not a requirement of the program. In addition, to enhance the individual projects as well as the program goals, it is envisioned that each TMRC, under the direction of the PD, will schedule regular meetings on at least a quarterly basis to foster scientific cooperation and collaboration.

3. TMRC Research Projects

Each TMRC must propose two or more scientifically meritorious projects whose interrelationship(s) will result in a greater contribution to the program goals than if each project were pursued individually. There must be a unifying, well-defined goal or problem area of research to which each project relates and contributes, thereby producing a research environment that allows each project to benefit from the creative strengths of the other(s). Each research project included in the application must, as assessed by peer review, stand on its own independent scientific merit, as well as complement the other project(s). Each of the individual projects within the TMRC will be under the leadership of an established, resident investigator who will also serve as the Project Leader for the specific project. Project Leaders are expected to expend at least 25% effort on their individual projects. In addition, research projects that involve substantial interactions with patient populations require clinicians and/or health care personnel with significant clinical research experience and skills to be responsible for patient safety and the conduct of the clinical study. All investigators must contribute to, and share in, the responsibilities of fulfilling the objectives of the TMRC.

4. Research Plan

Applicants must provide a detailed description of the proposed research project(s), including: (1) the pathogen or disease entity proposed for study; (2) evidence of a significant burden of disease in the area where the studies will be conducted; (3) the research question(s) to be addressed; (4) a description of the facilities available as needed for the proposed research projects; (5) the proposed methodology; (6) the study population, documentation of access to necessary patients and/or samples, and plans for the recruitment and retention of study participants; (7) quality control and analysis plans; and (8) training as required by investigators and field staff to conduct the proposed research. The Research Plan must also include the proposed timelines for the planning, implementation, conduct and completion of research projects.

At least one of the proposed projects must be a clinical study (see Research Objectives and Scope). Clinical trials are not allowed. Each clinical study must include a brief concept proposal, similar in format to a study protocol, limited to a maximum of 5 pages within the research plan, detailing the following aspects of the proposed clinical study:

Study Title
Name and role of the Project Leader
Names and roles of Associate Investigators
Hypothesis to be tested
Study objectives
Population
Clinical sites
Study design (not all parts may be relevant)

Eligibility/exclusion criteria
Sampling/stratification plan (if any)
Sampling and/or matching criteria for case-control studies
Number of subjects
Anticipated duration of recruitment phase
Anticipated duration of participation for each study participant
Total study duration
Primary endpoints/outcomes definitions
Secondary endpoints/outcomes definition
Study visit schedule, procedures and primary evaluations (including laboratory evaluations)
Sample size justification

Any proposed sub-studies
Data analyses planned

5. Oversight of Clinical Research

When clinical studies are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html . The full policy, including terms and conditions of award, is available at http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf ; Guidance for Compliance with NIAID Clinical Terms of Award at http://www.niaid.nih.gov/ncn/pdf/clintermguidance.pdf ; and the DMID Policies and Guidance for Data and Safety Monitoring at http://www.niaid.nih.gov/dmid/clinresearch/ .

Award of a grant does not constitute approval for initiation of human subjects research. TMRC investigators will be required to develop and conduct all studies involving human subjects using Good Clinical Practice Standards as defined and published by the International Conference on Harmonization (ICH) and adopted by the FDA (Federal Register Vol.62 No. 90 (5/9/97) (http://www.fda.gov/oc/gcp/guidance.html).

Prior to study initiation, NIAID staff will review all studies involving human subjects at two stages. The first stage will be a review of the concept proposal, and the second review will be carried out during protocol development process that will lead to a finalized study protocol. At both stages, a comprehensive review will include, but not be limited to, scientific content, design, safety, feasibility, statistical methods, adverse events reporting, and informed consent. Use of the appropriate NIAID protocol template, found at the http://www.niaid.nih.gov/dmid/clinresearch/ , is required. NIAID staff and resources will be used to perform site assessments, determine training needs, perform site monitoring, and provide support for safety and clinical oversight as needed. Other NIAID operational support may be made available based on need.

6. TMRC Administrative Core

The PD is responsible for overall administration, coordination and management of the TMRC program. A research administrator responsible for the daily administration and fiscal management should be included as part of the Administrative Core. The research administrator must be fluent in the English language. A well-developed administrative plan is integral to the TMRC success and must be clearly defined in the application. The plan should include a discussion of the structure and roles of administrative staff, including the training and experience of proposed staff and the functions to be performed. The TMRC Administrative Core will be responsible for managing, coordinating, and supervising the entire range of TMRC activities, monitoring progress, and ensuring that the overall project management plan is implemented effectively and within proposed timelines. This Administrative Core should clearly identify personnel and resources needed to oversee the entire TMRC program. The description must provide a clear and explicit discussion of how fiscal and other resources will be prioritized, allocated, and managed, how communications will be managed and facilitated, and how research related travel and training will be organized and budgeted. Each TMRC must have a well delineated organizational structure and administrative mechanisms that foster interactions among investigators, accelerate the pace of research, enable translation of basic research findings to clinical applications, and ensure a productive research effort.

In the proposed budget, applications must include funding for overall administrative staff and services, expenses for publications for collaborative efforts, communication expenses, travel related to meetings, training, coordination, monitoring activities, as well as administrative capacity to meet reporting and oversight needs of the program.

7. TMRC Data Management Core

A data management system and a full-time Data Manager must be present at the TMRC site. Applications must provide a detailed description of the existing or planned data management system. The data management system should ideally include: security features for controlled access to project data; a tracking system for data forms, activities, and study samples; double data entry of data forms; date and time stamping of all data records with electronic signatures; and audit trails to track all changes made to data records. In addition, it is expected that the staff of the Data Management Core will collaborate on the design, development and testing of databases and data management software, validation of the data system, training of data management and field personnel on data collection procedures and activities, maintenance of the database and software systems, documentation of changes, and preparation of standard operating procedures for all aspects of data management. Applications must also address how the system will be planned and implemented, as well as the time frame within which all design, development, testing, validation, and training activities will take place to achieve a fully operational data management system and appropriately trained staff. Applicants with inadequate data systems and data management support currently in place should budget between $50,000 and $75,000 in the first year of the program and between $25,000 and $50,000 in the second year of the program to ensure development of robust, secure and comprehensive data management systems and for related training needs. It is recommended that data management systems be developed using U.S. Food and Drug Administration guidelines on electronic records issued in 21 CFR part 11 (http://www.biotechnicalservices.com/downloads/21CFRpart11.pdf ). A large part of the computerized data management system should be implemented and tested by the end of the first year.

The application should provide a detailed description of the data collection procedures for the projects. Supervision, quality control/assurance, and practices to assure data integrity and data security for data forms as well as the computerized data should be described in detail. For studies involving specimen collection and testing, the application should provide a detailed data management plan for specimen labeling, coding, tracking, and archiving, and a quality management plan for specimen handling and testing.

As a part of this core, biostatistics support is required for assisting with protocol design, development and analysis. This support should provide for activities such as developing sampling designs, where appropriate, generating interim tables and preliminary statistical analyses for progress reports, and assisting with statistical issues related to laboratory testing and results. The TMRC must include a designated Biostatistician who must commit no less than 10% effort to the program.

8. TMRC Scientific Cores

Common shared resources, e.g., laboratory or clinical service facilities, may be requested as Scientific Cores. Such cores should be utilized by two or more projects within the TMRC.

9. Meetings

Annual International Research Meeting: Each TMRC PD and research administrator will represent his/her TMRC at an annual international research meeting organized by NIAID. These meetings will be held to: share advances in tropical disease research among the TMRC projects and other NIAID-supported tropical disease research programs and activities; discuss research needs and opportunities in this arena; and facilitate the development of new collaborative protocols that may include multi-center studies.

Annual Reverse Site Visits and Clinical Research Conferences: Each TMRC will have a required annual reverse site visit at the NIH in Bethesda, MD. Thus, provision should be made for the TMRC PD to make two trips to Bethesda, MD each year. In addition, on approval by the NIAID Program Officer, each TMRC may send up to two personnel to clinical research conferences or training programs each year. Such anticipated registration and travel costs should be identified in advance and built into the budget of the TMRC application. Other TMRC personnel are encouraged, but not required, to attend the annual international research meeting organized by NIAID, and travel support will be at the discretion of the TMRC.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the Specialized Center grant (P50) award mechanism(s). This mechanism supports all phases of research ranging from basic and developmental aspects to applied field and clinical research. The spectrum of activities comprises a multidisciplinary approach to a specific disease entity or biomedical problem area. Unless specifically stated to the contrary herein, all policies and requirements that normally govern the grant programs of the NIH will apply.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

2. Funds Available

The estimated total funds available for the first year of support for this RFA will be $2.6 million. In fiscal year 2007, the NIAID plans to fund approximately three to four TMRCs under this RFA. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory scientific progress and administrative compliance during the preceding years and availability of funds. Satisfactory progress and compliance will be assessed by NIAID staff, including review of material presented in annual reports and at a required annual reverse site visit. At this time, the NIAID has not determined whether or how this solicitation will be continued beyond the present RFA.

An applicant may request a project period of up to five years. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Also, please see the Allowability of Facilities and Administrative (F&A) costs for foreign and international organizations at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html) published in the NIH Guide, March 30, 2001. NIH now allows F&A costs for foreign and international awards. NIH provides limited F&A costs (8 percent of total direct costs less equipment) to foreign institutions and international organizations to support the costs of compliance with NIH requirements including, but not limited to, protection of human subjects and animal welfare. NIH will not support the acquisition of, or provide for depreciation on, any capital expenditures, or support the normal, general operations of foreign and international organizations.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

• For-profit organizations
• Non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Foreign Institutions

Non-US organizations and institutions must be located in areas endemic for leishmaniasis, Chagas Disease, or human African trypanosomiasis in order to be eligible to apply. Applications may be submitted by for-profit and not-for-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories and government agencies only if in the endemic country. To achieve the goals identified in the application, subcontract or consortium arrangements are permitted with other institutions.

To ensure uninterrupted conduct of the research studies and the safety of the study personnel, the TMRC should be located in a politically stable setting. Anticipated safety concerns and security threats should not impede the conduct of the research during the period of the award. In order to permit adequate NIH oversight and monitoring of the clinical studies, the country should not have experienced protracted U.S. State Department travel warnings (http://travel.state.gov/travel/cis_pa_tw/tw/tw_1764.html ) advising against travel to the country or the site where the TMRC is proposed.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

2. Cost Sharing or Matching

This program does not require cost sharing or matching funds.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

• Applicant institutions may not submit more than one application.
• The proposed TMRC must be focused on any one of the following diseases: leishmaniasis, Chagas Disease, or human African trypanosomiasis.
• Each TMRC must have a well-delineated organizational structure and administrative mechanism that foster interactions among investigators, accelerate the pace of research, enable translation of basic research findings to clinical applications, and ensure a productive research effort.
• Each TMRC must consist of two or more scientifically meritorious projects whose interrelationships will result in a greater contribution to the program goals than if each project were pursued individually. There must be a unifying, well defined goal or problem area of research to which each project relates and contributes, thereby producing a research environment that allows each project to benefit from the creative strengths of the other(s). Each research project included in the application must, as assessed by peer review, stand on its own independent scientific merit, as well as complement the other project(s). At least one of these projects must be a clinical study. Each TMRC is required to have an Administrative Core and a Data Management Core.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11."
• Funds for up to 8% administrative costs (excluding equipment) can now be requested (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html)
• Organizations must comply with federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with federal/NIH biosafety and biosecurity regulations. See Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

Proposed research should provide a unique research opportunity not available in the U.S.

Supplemental Instructions for the Preparation of Multi-project Applications

The following section supplements the instructions found in Form PHS 398 for preparing the multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research grant (R01) applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. These instructions can be found at http://www.niaid.nih.gov/ncn/grants/multi/index.htm .

The supplemental instructions below are divided as follows:

A. General Instructions addresses collaborative efforts among research projects, the administrative and organizational structure as well as the overall facilities and environment, and the overall budget.

B. Specific Instructions for Individual Projects describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

C. Specific Instructions for Core Units scientific cores must provide services or resources to support at least two research projects. Instructions describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

A. General Instructions

All applications must be submitted on Form PHS 398. The multi-project grant application should be assembled and paginated as one complete document.

1. Face Page

Items 1 - 15: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

2. Form Page 2

Using Page 2 of Form 398, provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator of the multi-project application, followed by the Project Leaders of the component research projects and cores, and then by other key personnel.

3. Form Page 3 - Table of Contents

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4. Composite Budget

Do not use Form Page 4 of PHS Form 398. Instead, using the suggested format presented below, prepare a Composite Budget For All Proposed Years of Support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

5. Form Page 5

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry.

6. Biographical Sketch Format Page

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the Principal Investigator first, followed by those of other key personnel in alphabetical order.

7. Other Support Format Page

Do not complete. (Any required information will be requested from successful applicants prior to grant award.)

8. Resources Format Page

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

9. Program Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 25 pages. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

10. Appendix

The Appendix is limited to a total of ten (10) documents or one hundred (100) total pages, whichever is less. All pages in reprints and other documents count as one page.

B. Specific Instructions for Individual Research Projects

1. Cover Page

The Face Page of the 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, a "Cover Page" containing selected data about each individual research project should be prepared. A Cover Page should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

Project Number and Title: (e.g., 1. Screening Test for TB)

Name of Project Leader: (e.g., Jones, Roberta A.)

Human Subjects: (Yes or No)
If Yes, exemption number: (e.g., 4)
(or)
IRB Approval Date: (e.g., 12/13/2006,or "Pending")
(and)
Federalwide Assurance (FWA) number:

Vertebrate Animals: (Yes or No)
If Yes, IACUC Approval Date: (e.g., 11/17/2006, or Pending)
(and)
Animal welfare assurance number:

Proposed Period of Support:
From: (mmddyy - e.g., 07/01/2007)
To: (mmddyy - e.g., 06/30/2112)

Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)
Direct Costs: (e.g., $ 150,000)
Total Costs: (e.g., $162,000)

Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)
Direct Costs: $700,000

Applicant Organization:
(full address)

2. Form Page 2

Provide a Description (abstract) of the research proposed in the project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the research project will contribute towards attainment of the multi-project program objectives.

For all other items in the individual project application, follow the usual PHS 398 instructions.

C. Specific Instructions for Cores

1. All Cores

Cover Page. The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core should be prepared. This cover page will demarcate each core. A Cover Page should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

Core Letter and Core Title
(e.g., A. Monoclonal Antibody Production Core)

Name of Core Leader
(e.g., Smith, Robert A.)

Human Subjects (Yes or No)
If Yes, Exemption Number
(or)
IRB Approval Date (e.g., 5/14/02, or Pending)
(and)
Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)
If Yes, IACUC Approval Date (e.g., 4/15/07, or Pending)
(and) Animal welfare assurance number

Proposed Period of Support
From: (mmddyy, e.g., 07/01/2007)
To: (mmddyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period
(e.g., Direct Costs: $50,000)
(e.g., Total Costs: $70,000)

Costs Requested for the Entire Budget Period
(e.g., Direct Costs: $212,323*)
(e.g., Total Costs: $297,252*)

Applicant Organization
(ABC University
111 Main Street
Anywhere, Else 99999)

The following are specific instructions for sections of the PHS 398 application form that are to be completed differently than usual. For all other items in the core application, follow the usual PHS 398 instructions.

Form Page 2. Provide a Description (abstract) of the Core activities and services according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the multi-project program objectives.

Form Page 3. Prepare a Table of Contents for the core using page 3 of Form PHS 398. Since the biographical sketches of all participating investigators will be located at the end of the overall application (and therefore should be referenced in the Overall Table of Contents), it is not necessary to repeat these pages.

Core Research Plan (Items A-D cannot exceed 25 pages)

• Item A - Specific Aims: List in priority order the broad, long-range objectives of the proposed core. In addition, state the core's relationship to the multi-project program goals and how it relates to the research projects or other cores in the application.
  
  
• Item B - Background and Significance: Use this section to describe how the proposed core activities will contribute to meeting the goals and objectives and explain the rationale for the selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the multi-project grant.

For all other items in the individual core application, follow the usual PHS 398 instructions.

2. Administrative Core

Each application must provide for an Administrative Core headed by the Project Director and responsible for the overall management, coordination and supervision of the TMRC program. A research administrator responsible for the daily administration and fiscal management should be included as part of the Administrative Core. The research administrator should be fluent in the English language and is required to devote 100% effort. Provide an administrative plan that includes a discussion of the structure and roles of administrative staff, including the training and experience of proposed staff and the functions to be performed, how fiscal and other resources will be prioritized, allocated and managed, how communications will be facilitated, and how research related travel and training will be budgeted.

Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, communication expenses, etc., should be requested here.

3. Data Management Core

Data Management System: Each application must provide for a Data Management Core that includes a data management system and a full-time Data Manager at the TMRC site. Applications must provide a detailed description of the existing or planned data management system, including: security features for controlled access to project data; a tracking system for data forms, activities, and study samples; double data entry of data forms; date and time stamping of all data records with electronic signatures; and audit trails to track all changes made to data records. Applications must also address how the system will be planned and implemented, as well as the time frame within which all design, development, testing, validation, and training activities will take place to achieve a fully operational data management system and appropriately trained staff. Applicants with inadequate data systems and data management support currently in place should budget between $50,000 and $75,000 in the first year of the program and between $25,000 and $50,000 in the second year of the program to ensure development of robust, secure and comprehensive data management systems and for related training needs. It is recommended that data management systems be developed using U.S. Food and Drug Administration guidelines on electronic records issued in 21 CFR part 11 (http://www.biotechnicalservices.com/downloads/21CFRpart11.pdf). A large part of the computerized data management system should be implemented and tested by the end of the first year.

Data Collection Procedures: The application should provide a detailed description of the data collection procedures for the projects. Supervision, quality control/assurance, and practices to assure data integrity and data security for data forms as well as the computerized data should be described in detail. For studies involving specimen collection and testing, the application should provide a detailed data management plan for specimen labeling, coding, tracking, and archiving, and a quality management plan for specimen handling and testing.

Other Data Management Core Functions: Describe the expertise, qualifications, experience and roles of the Data Manager and all other Data Management Core staff with respect to collaborating on the design, development and testing of databases and data management software, validation of the data system, training of data management and field personnel on data collection procedures and activities, maintenance of the database and software systems, documentation of changes, and preparation of standard operating procedures for all aspects of data management.

Biostatistics Support: Describe the expertise, qualification, experience and roles of the TMRC Biostatistician and any other biostatistical staff with respect to assisting with protocol design, development and analysis, including developing sampling designs, where appropriate, generating interim tables and preliminary statistical analyses for progress reports, and assisting with statistical issues related to laboratory testing and results.

4. Scientific Cores

A scientific core is a resource to the multi-project grant as a whole and must support at least two of the proposed research projects. The application must indicate the specific projects to be served by the Scientific Core(s). This section of the application should present a clear picture of the facilities, techniques, and skills that the core will provide and describe the role of the Core Leader and each of the key participants. The apportionment of dollars, or percentage of dollars, that will be required to support each component research project which will utilize each scientific core should also be presented.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Letters of Intent Receipt Date(s): June 21, 2006
Application Receipt Dates(s): July 21, 2006
Peer Review Date(s): November, 2006
Council Review Date(s): January, 2007
Earliest Anticipated Start Date: July, 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3136, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (USPS Express or regular mail)
Bethesda, MD 20817 ( for express/courier service)
Telephone: (301) 435-8537
FAX: (301) 402-2638
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 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)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3136, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (USPS Express or regular mail)
Bethesda, MD 20817 ( for express/courier service)
Telephone: (301) 435-8537
FAX: (301) 402-2638
Email: [email protected]

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the National Institute of Allergy and Infectious Diseases. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review

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. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of program priorities

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the National Institute of Allergy and Infectious Diseases in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by National Advisory Allergy and Infectious Diseases Council.

Review Criteria

Applications will be evaluated based on the following criteria:

1. Significance . Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

2. Approach . Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

3. Innovation . Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

4. Investigators . Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

5. Environment . Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Additional Review Criteria for the Overall Multi-project Grant Application

The relationship and contributions of each component research project and core to the overall theme of the multi-project grant application will be evaluated by the initial review group. This evaluation is a separate consideration from the merit evaluation of the individual projects and cores. Assessment of the overall application is conducted after all individual research projects in that application have been reviewed and rated.

Specific factors to be evaluated in the consideration of the overall multi-project application are as follows:

• What is the Scientific merit of the program as a whole, as well as that of the individual research projects.
• What is the Significance of the overall program goals.
• Are there demonstrations of Scientific gain achieved by combining the component projects into a multi-project program, beyond that achievable if each project were to be pursued independently.
• Does the application provide evidence of Cohesiveness and multi-disciplinary scope of the program and the coordination and interrelationships of all individual projects and core(s) to the common theme.
• Does the application provide evidence of the Leadership and scientific ability of the Program Director: ability to develop a program of integrated research projects with a well-defined central research focus, and commitment and ability to devote adequate time and effort to the program.
• Are the Qualifications, experience, and commitment of investigators responsible for the individual research projects or core(s) and their contribution to the program, appropriate for the proposed research program. Is their ability to devote time and effort to the program documented adequate and appropriate.
• For competing renewal and supplement applications, What are the accomplishments of the program to date and do they indicate appropriate productivity.

Review Criteria for the Administrative Core

• Does this have clearly delineated organizational structure and administrative mechanisms, which accelerate science, foster interactions and enable translation.
• Has they clearly described structure and roles of administrative staff.
• Do they show clear and explicit discussion of fiscal and other resource prioritization, allocation and management.
• Does the application provide evidence of adequate communications plans.
• Does the application provide evidence of adequate plans for facilitating and financing research related travel and training plans.

Review Criteria for Date Management Core

• Does the application adequately described security features, a tracking system, double data entry, date and time stamping and audit trails.
• Does the application provide evidence of qualified staff to collaborate on the design development and testing of databases and data management software, validation, training, maintenance of systems, documentation of changes and preparations of standard operating procedures
• Is there a clear description of panning and implementation of the system, as well as the time frame to achieve a fully operational data management system with appropriately trained staff
• Is there a detailed description of the data collection procedures, including specimen labeling, coding, tracking, archiving and quality assurance.
• Does the application provide evidence of adequate biostatistical support to provide assistance in protocol design, development and analysis with no less than 10% effort.

Review Criteria for Individual Scientific Cores

Each core unit must provide essential facilities or services for two or more individual research projects which have been judged to have significant and substantial scientific merit. Review criteria for scientific cores consist of the following:

• Does the application provide justification and usefulness of the core facilities to the various research projects.
• Do the show a good relationship in each core to the central focus of the overall program.
• Is there clear quality of relevant facilities or services provided by the core (including procedures, techniques and quality control) and criteria for prioritization and usage.
• Does the application provide evidence of clear qualifications, competence and commitment of the core leader and key personnel.
• Does the application provide evidence for the appropriateness of the budget.

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not Applicable

Section VI. Award Administration Information

1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See Also Section IV.5. Funding Restrictions.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Dr. Malla R. Rao
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 5095, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 451-3749
FAX: (301)402-0659
Email: [email protected]

2. Peer Review Contacts:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3136, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (USPS Express or regular mail)
Bethesda, MD 20817 ( for express/courier service)
Telephone: (301) 435-8537
FAX: (301) 402-2638
Email: [email protected]

3. Financial or Grants Management Contacts:

Donna Sullivan
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2112, MSC-7614
6700B Rockledge Drive|
Bethesda, MD 20892-7614
Telephone: (301) 594-6361
FAX: (301) 493-0597
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ in the following citations: No. 93.855, Allergy, Immunology and Transplantation Research and No. 93.856, Microbiology and Infectious Diseases Research, and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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