Part I Overview Information


Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID) (http://www.niaid.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov )

Title:  Clinical Trials in Organ Transplantation in Children (U01)

Announcement Type
This RFA is a re-issuance with modifications of RFA-AI-02-004, which was previously released on March 26, 2002.

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

Request For Applications (RFA) Number: RFA-AI-07-006

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.838

Key Dates
Release Date: January 12, 2007
Letters of Intent Receipt Date(s): May 14, 2007
Application Receipt Date(s): June 13, 2007
Peer Review Date(s):  October, 2007
Council Review Date(s): January, 2008
Earliest Anticipated Start Date(s): March, 2008
Additional Information To Be Available Date (URL Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/
Expiration Date:  June 14, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

 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
    A. Cooperative Agreement Terms and Conditions of Award
      1. Principal Investigator Rights and Responsibilities
      2. NIH Responsibilities
      3. Collaborative Responsibilities
      4. Arbitration Process
  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

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI) invite new and/or competing continuation applications from teams of institutions to participate in a clinical trials program to improve graft acceptance and patient/graft survival in pediatric organ transplant recipients, i.e., children up to 20 years of age, who have undergone heart, lung, liver, kidney or intestinal transplantation.  The Clinical Trials in Organ Transplantation in Children (CTOT-C) program will support a cooperative, multi-institutional consortium for the conduct of interventional or observational clinical studies with associated mechanistic studies, to further our understanding of and ultimately reduce the immune-mediated morbidity and mortality in pediatric transplant recipients.  These studies will be designed to: (1) evaluate new therapies and approaches to overcome immunologic barriers to graft acceptance and/or long-term graft and patient survival; (2) evaluate novel approaches to treatment or prevention of immune mediated complications in pediatric transplant patients; (3) investigate underlying mechanisms of action for pathological processes and therapeutic regimens under evaluation; and (4) develop diagnostic tests and critical biomarkers that will facilitate routine surveillance, early diagnosis and ongoing monitoring of those processes that contribute to post-transplant morbidity and mortality.

NOTE:  This RFA will NOT support:  (1) studies of hematopoietic stem cell transplantation (HSCT) unless HSCT is a component of a study of organ transplantation; (2) studies of islet transplantation for treatment of type 1 diabetes; (3) studies involving animal models unless they are directly linked and necessary to achieve specific aims of a clinical trial; and (4) studies involving xenotransplantation.

Background

Organ replacement is presently the best treatment for end-stage organ failure in the absence of suitable alternative therapy.  In recent decades, organ transplantation in children has been associated with improved early survival and quality of life, though these advances have sometimes lagged behind similar progress in adult populations.

Despite marked improvements in one-year survival and a reduced incidence of acute rejection, the average half-life of an allograft is only 10 - 12 years, varying from organ to organ.  Little progress has been made in reversing the inexorable long-term decline of graft function and the reduced life expectancy of organ transplant recipients. This is largely due to the morbidities associated with long-term pharmacologic immunosuppression, such as infection, hypertension, diabetes mellitus, renal damage, hyperlipidemia, cardiovascular disease and malignancy.  Long-term effects of chronic steroid use and other immunosuppressive agents - stunting of growth, changes in body habitus, altered intellectual development, interruption of schooling, medical non-adherence, and psychosocial sequelae - are particularly deleterious in the pediatric population.

There are almost 100,000 individuals listed for organ transplantation in the United States.  Approximately two percent are children under the age of 21 years.  These children are exposed to the same pharmacologic and surgical interventions as their adult counterparts, but may have unique needs and characteristics including immunologic immaturity, naïveté to multiple infectious pathogens, differences in drug metabolism, and issues related to physical growth and psychological development.  Their relatively small number makes clinical investigation of pediatric transplant recipients quite challenging and also makes it unlikely that their specific needs will be addressed in the absence of a focused initiative.

In 1993, NIAID established the “Cooperative Clinical Trials in Pediatric Transplantation” (CCTPT) program, a consortium conducting clinical trials in pediatric kidney transplantation.  This endeavor focused on drug minimization in pediatric kidney recipients, pediatric pharmacokinetics, and studies of immune mechanisms.  CCTPT has succeeded in developing a reliable network of clinical centers for pediatric transplant research.  CCTPT trials have demonstrated that research kidney biopsies can be performed safely in children and that calcineurin inhibitor-free regimens can provide effective protection from kidney rejection in children.  This renewal of CCTPT, renamed CTOT-C, is expanded to include studies in all pediatric organ transplant recipients.

The CTOT-C consortium will work collaboratively with the Clinical Trials in Organ Transplantation (CTOT) consortium (www.CTOTstudies.org ) (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-04-003.html), a similar clinical studies program in adult organ transplantation. The collaboration is expected to benefit both groups; CTOT-C will provide the necessary pediatric expertise and advocacy for the CTOT, and under certain conditions may be able to leverage statistical power from concurrent studies in adults. 

Research Objectives and Scope

Responsive applications to this RFA will propose multi-center clinical trials and/or observational studies, with associated mechanistic studies, which will improve our understanding of and/or evaluate interventions to reduce the immune-mediated morbidity and mortality of solid organ transplantation in children.  Mechanistic studies associated with these clinical trials and observational studies should specifically address the underlying immunologic issues.  Examples of clinical trials and observational studies include, but are not limited to:

Each clinical study proposed (See Section IV.6.2. Application and Submission Information-Other Submission Requirements) must include associated mechanism of disease and/or therapeutic action studies.   Examples of associated mechanistic investigations include, but are not limited to:

Applications proposing such studies will be considered non-responsive and will be withdrawn from further consideration without peer review. The applicant will be informed of this action. 

Applicants are strongly encouraged to contact program staff listed under Section VII.1Agency Contacts, well in advance of the application receipt date to allow staff to assess responsiveness to this RFA and provide appropriate guidance as needed.

Data Coordination and Management

Data coordination and management will be carried out by a separately funded data coordinating center, the Statistical and Clinical Coordinating Center (SACCC) (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-04-046.html).  Each participating institution will be responsible for providing primary study data to the SACCC. Timeliness and accuracy of submitted data will be monitored by the SACCC and evaluated by the Steering Committee.  SACCC responsibilities are further described under Section VI 2.A.3, Cooperative Agreement  Terms and Conditions of Award – “Collaborative Responsibilities.”

Steering Committee

A Steering Committee will serve as the governing board for the CTOT-C consortium; its actions and decisions will be determined by majority vote. The Steering Committee will develop policies and procedures governing the activities of the consortium. Steering Committee responsibilities are further described under Section VI 2.A.3, Cooperative Agreement Terms and Conditions of Award – “Collaborative Responsibilities.” 

Mechanistic Studies Subcommittee 

The Steering Committee shall appoint a Mechanistic Studies Subcommittee to review proposed mechanistic studies and make recommendations to the Steering Committee.  Each Principal Investigator shall select one representative from his/her team as a voting member of the Mechanistic Studies Subcommittee; additional non-voting members may be nominated and approved by the Steering Committee.  Mechanistic Studies Subcommittee responsibilities are further described under Section VI.2.A.3. Cooperative Agreement Terms and Conditions of Award – “Collaborative Responsibilities.”

Publications Subcommittee

The Steering Committee will establish a Publications Subcommittee to develop publication policies and procedures for the CTOT-C consortium. Publications Subcommittee responsibilities are further described under Section VI.2.A.3. Cooperative Agreement Terms and Conditions of Award – “Collaborative Responsibilities.”

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 U01 award mechanism(s).

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.


The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI.2.A Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award.”  

At this time, NIAID has not determined whether and how this solicitation will be continued beyond the present RFA. 

2. Funds Available

The NIAID and NHLBI intend to commit approximately $3.5 million in FY 2008 to fund three to four new and/or competing continuation grants in response to this RFA.  An applicant may request a project period of up to five years and a budget for direct costs up to $800,000 per year.  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.   Although the financial plans of the NIAID and NHLBI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.  The anticipated start date is March 2008.   

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

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:

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 support. Principal Investigators must be established in the field of pediatric transplantation as evidenced by clinical experience and relevant publications.  

2. Cost Sharing or Matching

Cost sharing is not required.

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

A Principal Investigator may submit only one application.  A Principal Investigator may serve as a collaborator on another application provided there is no scientific overlap.  An investigator may serve as Principal Investigator on only one application. An institution may submit only one application as the applicant institution, but may participate on multiple applicant teams.  An institution may serve as an applicant institution on only one application.   

The applicant team must contain three or more participating institutions working together with a designated Principal Investigator.

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) 435-0714, Email: GrantsInfo@nih.gov.

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.

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): May 14, 2007
Application Receipt Date(s): June 13, 2007
Peer Review Date(s):  October, 2007
Council Review Date(s): January 2008
Earliest Anticipated Start Date(s): March, 2008
 
3.A.1. Letter of Intent

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

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 NIAID 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:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Tel: 301-496-8426
Fax: 301-480-2408
Email: pjackson@niaid.nih.gov

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:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Tel: 301-496-8426
Fax: 301-480-2408
Email: pjackson@niaid.nih.gov

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 NIAID. 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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

Applications must contain the following sections, in order, with page limits where indicated: (1) Documentation of Commitment to the Collaborative Group [1 page]; (2) Research Plan [25 pages]; (3) Scientific Agenda [2 pages]; (4) Applicant Group Qualifications, Organization and Administration (10 pages); and (5) Collaboration with the CTOT [2 pages]. Each section is described below:

1.  Documentation of Commitment to the CTOT-C Collaborative Group (1 Page)

The application must include a written commitment, signed by the Principal Investigator and the applicant institution, to participate in the CTOT-C consortium, including serving on the Steering Committee, adhering to Steering Committee policies and decisions, and accepting the participation and assistance of NIAID staff in accordance with the guidelines described in Section VI.2.A.3. Cooperative Agreement Terms and Conditions of Award:  “Collaborative Responsibilities.”

2.  Research Plan (25 Pages)

a.   Concept proposals for clinical studies

Research plans for interventional or observational clinical studies with associated mechanistic studies must be in the form of detailed concept proposals, organized as specific aims, background and significance, preliminary studies, and research design and methods.  All proposed clinical studies and associated mechanistic studies must be presented within a single Research Plan section not to exceed 25 pages in length.  Concept proposals must be presented in sufficient detail to allow reviewers to judge significance, approach, innovation, and environment.  Methods of data analysis and sample size justification for the proposed clinical study, must be included.  Submission of a detailed, final clinical protocol is neither required nor encouraged, as the choice of studies to be performed and final protocol development will be accomplished subsequent to award, under the guidance of the Steering Committee. 

The application must include a concept proposal for one or more interventional or observational clinical studies with associated mechanistic studies that meets the objectives and scope of this RFA.   Proposals may involve study of a single type of organ transplant or may be designed to address a transplant-related immunologic problem that will be studied in a diverse group of pediatric organ recipients.  The proposed clinical study may involve a clinical intervention or may be an observational study.  The proposed study or studies must not exceed the clinical and scientific resources of the applicant’s team of institutions and must not exceed 5 years in duration.

The concept proposal must include the following information about the clinical study or studies:

b. Accompanying mechanistic studies

Each clinical proposal must be accompanied by mechanistic studies designed to expand our understanding of the basic mechanisms of alloimmunity, innate immunity in the transplant setting, and/or graft dysfunction. Mechanistic studies will be weighed equally with the interventional or observational clinical studies in the review of the application.

 Descriptions of proposed mechanistic studies must include:

The applicant must clearly state how anticipated study results can be expected to contribute to improvements in patient/graft survival.

Each proposed mechanistic study must include:

3.  Scientific Agenda (2 Pages)

Applicants must briefly present their views of the important questions facing the field of pediatric transplantation and explain how their proposed research addresses these questions (may not exceed 2 pages).  These responses will assist the Steering Committee in creating a scientific agenda for the overall CTOT-C consortium post award.

4.  Applicant Group Qualifications, Organization and Administration (10 pages)

a. The applicant team must contain three or more participating institutions, or must provide evidence that the resources of fewer centers are sufficient to support the clinical and mechanistic studies described in the application.  Member institutions may be clinical participants, in which case they must provide documentation of a United Network for Organ Sharing (UNOS) certified program in organ transplantation, or they may be mechanistic study participants, in which case they must have demonstrated expertise in the research techniques necessary for the proposed mechanistic studies and research agenda. 

b. The applicant institution and each institution participating in the applicant’s team must document clinical experience, capacity to recruit and retain pediatric study participants, and provide a description of the population currently available for each proposed study.  This information should include annual numbers of all pediatric organ transplants performed (by organ) at each clinical site for the last five years.  Furthermore, the applicant and participating institutions must explicitly state that the approved trials within the CTOT-C will have priority over any subsequent non-CTOT-C study in pediatric organ transplantation.  Exemptions from this agreement will require approval by the NIAID and the Steering Committee. 

c. The applicant must document availability of personnel and facilities capable of performing and supporting administrative functions for the overall management of the applicant group.

d. The application must name a single Principal Investigator who will have scientific responsibility for the application as a whole, including all team-related research activities.  The Principal Investigator must be a physician with substantial experience in pediatric organ transplantation and in the design, implementation, and evaluation of clinical trials.

e. Applications must name a single Senior Investigator for each participating institution in the applicant’s group or team that will be responsible for on-site clinical and scientific implementation, direction and management of the clinical protocols, and the coordination of requirements for mechanistic studies of underlying mechanisms and immune/surrogate markers.  A letter from each Senior Investigator, indicating a commitment to participate and the qualifying characteristics of his/her institution, must be included with the application.

f. The applicant must provide a clear and concise plan, in narrative and diagrammatic form, that depicts the interrelationships among the members of the team or group, their relevant experience/expertise, and the contribution of each to fulfillment of the objectives of this RFA, as well as an organizational chart of the team or group showing the name, organization, and scientific discipline of the Principal Investigator and all key scientific, technical and administrative personnel.

g. The applicant must provide a plan to ensure the maintenance of close cooperation and effective communication among members of the applicant’s group; letters of commitment to this plan from all participating institutions; and evidence of the capability of the applicant organization and each institution in an applicant group to participate and interact effectively in cooperative, multi-center clinical trials.

5. Collaboration with the CTOT (2 Pages)

The applicant must describe how the CTOT-C consortium will establish a productive collaboration with the CTOT. Information about the CTOT is available at http://www.ctotstudies.org, and at (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-04-003.html),

Additional submission requirements for the preparation of the Detailed Budget:

Study Costs

All costs required for the concept proposals and mechanistic studies must be included in the application and must be fully justified.  These include the costs of the proposed clinical research, costs for patient recruitment and follow-up, mechanistic studies, data collection, and participation in on-site quality assurance audits.

The budget must include support for a clinical study coordinator at each clinical site, with effort proportional to the anticipated volume of patient enrollment at that site, but in no case less than 20% effort per site.

Mandatory Meetings

Requested budgets should also include funds for:  (1) travel to the Bethesda, MD area for two Steering Committee meetings during the first 12 months, and annually thereafter, for the Principal Investigator and one Senior Investigator from each participating institution, and (2) travel to the Bethesda, MD area for two Mechanistic Studies Subcommittee meetings per year for the Principal Investigator and one representative from the applicant’s group.

Foreign Institutions

Applications from groups that include foreign institutions must provide the following information:

a.       If a study requiring an IND (Investigational New Drug) application is proposed, the application must provide information regarding the costs associated with maintaining a legal entity in the foreign country, submission to the foreign health authority, and required insurance coverage for clinical trials.

b.       All foreign sites must provide information about the availability and cost of clinical site monitoring in the foreign country.

c.        The above costs must be included in the study budget.

Applications lacking the information described above, as determined by NIAID staff, will be designated as non-responsive to the RFA and will be withdrawn from further consideration without peer review. The applicant will be informed of this action. 

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.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may 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 expects that grant 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

Only the review criteria described below will be considered in the review process.  The following will be considered in making funding decisions:

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 NIAID in accordance with the review criteria stated below.

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

·         Receive a second level of review by the advisory councils of NIAID and NHLBI.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important scientific health 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? 

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?  

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?

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)?  Does the Principal Investigator have adequate, appropriate expertise and contributions to the field of pediatric organ transplantation?  Does the Principal Investigator have prior experience with multi-center clinical trials?  Is the Principal Investigator committed to the collaborative effort and able to provide the leadership necessary to achieve multi-site adherence in a clinical trial research protocol?  Do the mechanistic study investigators have expertise and prior experience with the conduct of mechanistic studies pertaining to the immunologic areas under study using human specimens?  Do the mechanistic studies investigators have research experience in basic immunologic aspects of transplantation as demonstrated by authorship of publications?”

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?  Is the relationship among the applicant group members clearly defined?  Are there adequate plans for cooperation and effective communication among applicant group members?

Concept Proposal for Clinical Studies and Associated Mechanistic Studies:  Are the rationale and scientific merit of the concept proposal for the clinical study or studies, and the associated mechanistic studies well developed and feasible? If implemented, will the proposed studies advance pediatric organ transplantation? Are there adequate and feasible plans for managing the proposed studies, plans for recruitment and retention of study participants?  Does the applicant adequately address the overall approaches to overcoming obstacles and limitations with respect to these activities?

Participating Clinical SitesDo the clinical sites have demonstrated knowledge of clinical organ transplantation in pediatric patients as evidenced by clinical experience, transplant outcomes, and scientific publications?  Does the site have a UNOS-approved transplant program?  Are the clinical sites specialized pediatric centers and/or institutions with extensive experience and expertise in pediatric solid organ transplantation?  Is their any evidence of successful experience in recruitment and retention of research subjects in multi-center clinical studies, and particularly studies of clinical organ transplantation in children?  Is their documentation of center volume adequate to contribute at least 10 pediatric subjects per year to the proposed studies?  What clinical and scientific resources does the site bring to the applicant team?

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 may 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 funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy expects that grant 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).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 U01, 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.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have primary responsibility for: (1) determining and coordinating the project activities scientifically and administratively; (2) setting project goals and timelines to achieve the proposed goals, (3) attending Steering Committee meetings, serving as a voting member of the Steering Committee, and accepting and implementing policies and procedures developed by the Steering Committee; (4) providing primary study data to the SACCC for management, quality control, and analysis; (5) submitting data to NIH-supported and/or public databases in accordance with policies agreed upon and established by the Steering Committee and the NIH data sharing policy available at: http://grants.nih.gov/grants/policy/data_sharing/; and (6) participating in the cooperative nature of the group.  It is recognized that goals may require revision and re-negotiation during the course of the project period.  Release of each funding increment by NIAID will be based on a review of progress towards achieving the previously agreed upon research goals.

Monitoring Clinical Studies

When clinical studies or trials 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, and terms and condition of award, are available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf. Local institutional review boards and the NIAID Data and Safety Monitoring Board (DSMB) must approve clinical protocols before initiation.

Data

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 HHS, PHS, and NIH policies.  However, awardees must be committed to making the biological samples, diagnostic products, and other research tools, methods, data, and materials that are developed under CTOT-C awards available to the CTOT-C and the research community.

2.A.2. NIH Responsibilities

The NIH Project Scientist will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants.

During performance of the award, the NIH Project Scientist, with assistance from other scientific/medical/regulatory program staff who are designated based on the research topic and their relevant expertise, may provide appropriate assistance, advice, and guidance by: participating in the design of the activities; advising in the selection of sources or resources; coordinating or participating in the collection and/or analysis of data; advising in management and technical performance; or participating in the preparation of publications.  However, the role of NIAID will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and the NIAID staff will be given the opportunity to offer input into this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator and the Steering Committee.

The NIH Project Scientist will serve as voting members of the Steering Committee and the Mechanistic Studies Subcommittee, schedule the first meeting of the Steering Committee, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies. 

Collaborations with industry will usually require the assistance of the NIAID Division of Allergy, Immunology and Transplantation (DAIT) Clinical Research Program, and be conducted under an NIAID Clinical Trials Agreement.

The NIAID reserves the right to terminate or curtail a study or any individual award in the event of: (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol; (b) substantive changes in the consensus protocol to which the NIAID does not agree; (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance; or (d) human subject ethical  or safety issues that may dictate a premature termination.

The NIAID DAIT Chief of Regulatory Affairs or designee will be responsible for providing guidance and assistance in the development, assembly and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist. The program official will monitor program progress, approve changes, and have access to data generated under these awards. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the group.

Data and Safety Monitoring Board (DSMB)

An independent DSMB, appointed by NIAID, will review progress at least annually and report its findings to the NIH Project Scientist.  Clinical protocols and mechanistic studies will be subject to review by the DSMB, in an advisory capacity, prior to implementation.  The DSMB review will focus on safety, ethics, scientific and statistical integrity of the studies.

Cooperation with Other NIH-Sponsored Programs

 In order to most efficiently utilize research resources and rapidly exchange scientific information to promote organ transplantation objectives, it is anticipated that awardees will collaborate with other NIAID funded programs, such as the CTOT.  The NIH Project Scientist will facilitate liaison activity for collaborations, and provide assistance with access to NIAID-supported resources and services.

2.A.3. Collaborative Responsibilities

Steering Committee

The Steering Committee will meet at least twice in the first year and annually thereafter in Bethesda, MD.

Mechanistic Studies Subcommittee

The Steering Committee shall appoint a Mechanistic Studies Subcommittee to review proposed mechanistic studies and make recommendations to the Steering Committee.  Each Principal Investigator shall select one representative from his/her consortium as a voting member of the Mechanistic Studies Subcommittee; additional non-voting members may be nominated and approved by the Steering Committee. The NIH Project Scientist will serve as voting members.  The Mechanistic Studies Subcommittee may ask the Steering Committee to appoint ad hoc subcommittee members if additional expertise in specific areas is needed.  The Mechanistic Studies Subcommittee shall elect a Chair from among non-Federal members.  The Mechanistic Studies Subcommittee will meet at least twice yearly and its members will be expected to participate in all meetings, conference calls and other subcommittee activities.

Publications Subcommittee

The Steering Committee will establish a Publications Subcommittee to develop publication policies and procedures for the CTOT-C consortium.

Data Coordination and Management

Data coordination and management will be carried out by a separately funded data coordinating center, the Statistical and Clinical Coordinating Center (SACCC).  Each participating institution will be responsible for providing primary study data to the SACCC for management, quality control and analysis using procedures and standards determined by the Steering Committee and the SACCC. The SACCC will provide technical assistance and data management services to participating institutions with respect to quality control, uniformity of data collection, management of the collective database and data analysis; centralized data collection and management; and quality assurance.  The SACCC will develop a statistical analysis plan for each approved study protocol that will be reviewed and approved by the Steering Committee.  In the event of a specific safety concern, the DSMB may also request specific analyses from the SACCC.  All participating sites will have access to all data originating from their sites.  The awardees will retain custody of and have primary rights to their data developed under these awards subject to government rights of access consistent with HHS, PHS and NIH policies.  The participating institutions will be closely involved with these centralized data collection and management services, and are responsible for on-site data collection and transmittal. The performance of participating institutions with respect to data submission, data quality, and protocol compliance will be monitored by the SACCC using criteria developed by the Steering Committee; these data will be provided to the PIs and evaluated by the Steering Committee at regular intervals.

2.A.4. Arbitration Process

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 arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

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:

Jonah Odim, MD, PhD
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases

Room 3041, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: 301-451-3138
FAX: 301-402-2571
Email: odimj@niaid.nih.gov

Nancy D. Bridges, M.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Room 3039, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: 301-451-4406
FAX: 301-402-2571
Email: nbridges@niaid.nih.gov

2. Peer Review Contacts:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Tel: 301-496-8426
Fax: 301-480-2408
Email: pjackson@niaid.nih.gov

3.
Financial or Grants Management Contacts:

Leslie Boggs
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2110, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-402-6450
FAX: 301-493-0597
Email: boggsl@mail.nih.gov

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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 RFA 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:  93.855, Immunology, Allergy, and Transplantation Research and 93.838, Lung 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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