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 Child Health and Human Development (NICHD), (http://www.nichd.nih.gov)
Office of Research on Women’s Health (ORWH), (http://orwh.od.nih.gov/)

Title: Cooperative Multicenter Reproductive Medicine Network (U10)

Announcement Type
This announcement for the Reproductive Medicine Network (RMN) is a re-issue of RFA-HD-99-005, released on May 4, 1999.

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

Request For Applications (RFA) Number: RFA-HD-06-008

Catalog of Federal Domestic Assistance Number(s)
93.865

Key Dates
Release Date: March 9, 2006
Letters of Intent Receipt Date(s): August 25, 2006
Application Receipt Dates(s): September 25, 2006
Peer Review Date(s): February/March 2007
Council Review Date(s): June 2007
Earliest Anticipated Start Date: July 1, 2007
Additional Information To Be Available Date (Url Activation Date): March 31, 2006
Expiration Date: September 26, 2006

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

The National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women’s Health (ORWH) invite investigators willing to participate, with the assistance of staff of NICHD under cooperative agreements, in an ongoing multicenter cooperative program designed to conduct clinical studies investigating problems in reproductive medicine, including infertility, such as causes of infertility and outcomes of infertility treatments; gynecological diseases and disorders; and diseases and disorders of the male reproductive system, particularly those that impact fertility. Disorders in the endocrinological system that affect reproduction are also within the scope of investigation for the Reproductive Medicine Network.  The objective of this program is to facilitate resolution of these problems by maintaining a network of sites that, by rigorous patient evaluation using common protocols, can study large numbers of patients and provide answers more rapidly than individual sites acting alone. The benefit of this activity will be to the public: individuals with reproductive diseases and disorders, infertile couples, and their health care providers.

Background

The mission of the Reproductive Sciences Branch is to ensure the birth of healthy, wanted babies through studies on human fertility and infertility. Additionally, the Branch supports research on common reproductive disorders that affect fertility as well as research into improving outcomes of infertility treatments.

In several aspects of reproductive medicine, particularly in the field of infertility, uncontrolled, trial and error methods have led to undeserved claims of efficacy and resulted in significant costs, both human and financial. With the development and wide acceptance of intracytoplasmic sperm injection (ICSI) for the treatment of male factor infertility, male patients are often not fully evaluated and given the option of less costly interventions. And there are few options available for the diagnosis and treatment of clinically normal men with a sperm defect.

There are gynecologic conditions that result in significant morbidity, particularly in women of reproductive age. Conditions such as endometriosis, leiomyomata uteri, abnormal uterine bleeding, pelvic floor disorders and others that cause pain, disruption of function in the workplace and the home and other problems beyond or beside effects on fertility. Many of these conditions can lead to hysterectomy or other major surgery. In some cases, alternative management strategies might have been effective, but were not understood, accessible or affordable.

In an attempt to provide well-designed clinical trials in reproductive medicine, the NICHD established the Reproductive Medicine Network in 1989. Eight clinical sites, plus a Data Coordinating Center, were awarded in response to the RFA. They have conducted trials on intrauterine vs. intracervical insemination, semen analysis as a measure of fertility, the utility of endometrial biopsy in infertility evaluation, and are conducting an ongoing trial on the efficacy of clomiphene citrate in combination with metformin as a treatment for infertility resulting from polycystic ovary syndrome.

Scope

The NICHD plans to extend the RMN, through a competitive, peer-reviewed process, for an additional five years to support clinical trials in reproductive medicine. Each RMN clinical site is expected to cooperate with the Data Coordinating Center (DCC) and NICHD staff to design and conduct clinical trials relevant to reproductive medicine. It is expected that current ongoing trials within the RMN will continue into the continuation grant period for successful existing centers. Centers that join the Network in the next award period may participate in protocols ongoing at that time.

Projects responsive to this solicitation would address clinical problems in reproductive medicine, including infertility; gynecological diseases and disorders; diseases, disorders of the male reproductive system; and disorders in reproductive endocrinology. The following are intended only as examples and should not be considered exclusive areas of interest:

Since this list is not meant to be all-inclusive, potential applicants are encouraged to discuss their potential research interests with the program staff listed under Section VII.  Agency Contacts.

A Data Coordinating Center (DCC) will provide a broad range of support services to the RMN in accomplishing its goal. It will serve to centralize and standardize the data that are derived from collaborative studies and will put the data sets into a common format that will facilitate their use by RMN member projects. The DCC will also serve as a collaborative member of the RMN by assisting in the statistical planning and implementation of clinical protocols and by providing logistical services to the RMN members as required by the multi-center research program. The DCC will assist with the preparation of Data and Safety Monitoring Committee (DSMC) reports, scientific manuscripts and other reports and documents as needed to support the goals of the RMN clinical sites. Additionally, the DCC will serve as a data archive to preserve the data for future secondary analyses and for access by the outside community.

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 NIH Cooperative Clinical Research (U10) 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 U10 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. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".  At this time, it is not known whether this funding opportunity will be re-issued. 

2. Funds Available

The NICHD and ORWH intend to commit approximately $6.6 million in FY 2007 to fund eight to ten new and/or competing continuation grants in response to this RFA for clinical sites, in addition to one new or competing continuation grant for the Data Coordinating Center (DCC). An applicant for a clinical site may request a project period of up to five years and a budget for direct costs associated with base costs up to $200,000 per year.  An applicant for the DCC may request a project period of up to five years and budget for direct costs up to $500,000 per year; in addition, the DCC should request not more than $2 million per year in Years 02 through 05 in the patient care category for distribution of per-protocol costs to the clinical sites for approved protocols.

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 NICHD and ORWH 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.

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:

An institution may apply for both a Clinical Site and the Data Coordinating Center (DCC) grant; however, separate applications with different Principal Investigators are required for each.  The DCC application must include a specific plan for maintaining the independent operation of each unit. 

Applications are welcome from both current members of the RMN (competing continuation applications) and from prospective members (new applications).

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

The Principal Investigator of a clinical site application must be a physician with clinical expertise related to reproductive medicine in women and/or men.

The Principal Investigator of the DCC must have appropriate expertise and capability in biostatistics, clinical study design, study development and support, data management, data analysis and project management.

2. Cost Sharing or Matching
Not applicable

3. Other-Special Eligibility Criteria
Not applicable

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): August 25, 2006
Application Receipt Dates(s): September 25, 2006
Peer Review Date(s): February/March 2007
Council Review Date(s): June 2007
Earliest Anticipated Start Date: July 1, 2007

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 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:

Tracy L. Rankin, Ph.D.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B-01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)

Telephone: (301) 435-6979
FAX:  (301) 480-2389:
Email:  rankint@mail.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:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510 
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)

Telephone: (301) 496-1485
FAX: (301) 402-4104
Email: stretchr@mail.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 the NICHD. 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

Data Coordinating Center (DCC)

The NICHD invites applications from the current member DCC of the RMN (competing continuation application) and from prospective members (new applications).   The application for the DCC should contain an introduction; either a progress report (competing continuation application only) or a description of the relevant capabilities and experience (new application) and a research plan for the next competitive funding period.

Scope:

The DCC will provide support in the following areas:

a) Study Design, Conduct, Analyses and Publications: The DCC will be responsible for providing statistical leadership and for developing innovative clinical trial design and analyses methodologies consistent with the RMN research agenda; assistance with protocol and manual of operations development; developing a data and safety monitoring plan for each implemented protocol; developing and implementing a plan for adverse event reporting in coordination with NICHD staff; performing interim analyses of safety and efficacy for the Data and Safety Monitoring Committee, NICHD and the Steering Committee; conducting final analyses and participating on publication writing teams; producing study monitoring reports for the Steering Committee and NICHD; and conducting analyses and summaries of annual and interim reports for NICHD-sponsored Investigational New Drug Applications (IND) in cooperation with NICHD staff.

b) Data Management: Provide central registration and randomization for all study subjects as required by study protocols; develop case report forms and standardized criteria for clinical endpoint verification; design and implement systems for the efficient tracking and transfer of clinical and laboratory data to the central database; provide data management training to the clinical sites; provide for central storage, security, processing and retrieval of study results; and prepare selected public access databases.

c) Site Monitoring: Initiate, monitor and close out clinical sites to assure Good Clinical/Laboratory Practice; audit clinical sites and provide reports to the NICHD and the Steering Committee

d) Regulatory Requirements: The DCC will work with NICHD staff by providing them with clinical study data, reports, and other support as required for Adverse Event Reporting and IND submissions.

It is expected that the successful applicant will possess a broad range of expertise and bring perspectives to the RMN that will inform group decisions and accelerate the pace of progress toward moving promising therapies into clinical practice. Specifically, applicants must have demonstrated capability in providing the types of support outlined above for multi-center trials. DCC applicants should also demonstrate biomedical knowledge relevant to reproductive medicine.

Minimum Requirements:

At a minimum, the application for the DCC should address the following:

a) Evidence of Successful Past Performance: Applicants must demonstrate prior experience in the design, conduct, data analysis, and data management of collaborative clinical research projects.  This includes protocol and manual of operations development, staff training in study procedures, data collection and management, quality assurance, data analysis, electronic communications, administrative management and coordination.  Experience with clinical trials in reproductive medicine is preferred, but not required. 

b) Appropriate Staff Expertise and Capability: The DCC will consist of a Principal Investigator, a project coordinator, and other staff deemed necessary to carry out its mission. The proposed DCC staff must be prepared to cooperate effectively in all network functions with NICHD and the RMN clinical sites. The Principal Investigator and other staff must have appropriate expertise and capability in biostatistics, clinical study design, study development and support, data management, data analysis and project management, including site training and quality assurance procedures.

c) Capacity and Ability to Manage Data and Communications: Applicants must have the ability to assist in designing study protocols, data collection forms, manuals of operation, and data collection systems. Additionally, they must have experience in developing and maintaining data quality control systems. Applicants must also provide plans for supporting a web-based communications system to members of the Network, as well as a data-sharing plan to make aspects of the trial data available to the outside community.

d) Evidence of Reporting and Publications Capabilities: RMN DCC applicants must provide evidence of their capacity to generate quarterly reports on subject enrollment for several concurrent studies; appropriate reports for the DSMC, Advisory Board and the Steering Committee meetings; and other special reports, as required. Applicants must also provide evidence of their ability to conform to all regulatory requirements in the conduct of clinical research, including safety and IND applications and reports.

e) Experience in Providing Logistical and Other Support Services: Applicants must be able to provide meeting and conference support for the activities of the Steering Committee, the Advisory Committee and the Data and Safety Monitoring Committee through the provision of materials and documentation, meeting planning and logistics, and conference call coordination.

f) Evidence of On-site Monitoring Capabilities: Applicants must have experience and demonstrate capability in organizing and conducting on-site monitoring of multi-center research studies

g) Evidence of Management Capability: Applicants must demonstrate their capability to assist the RMN Network to i) estimate appropriate and reasonable resources needed for individual projects; ii) manage those resources efficiently during the research; and iii) report these resource allocations to NICHD periodically.

Budget:

The DCC budget should be prepared for five 12-month periods.  The budget justification for each year should include a table that apportions the direct costs among the following categories:  core costs, costs of protocol initiation, and costs of protocol support.  Applicants should assume that one to two protocols will be initiated and active in the second year, including one randomized clinical trial.  Data Coordinating Center budgets should include:

The first year budget is limited to a maximum of $500,000 in direct costs with a limit of three percent escalation in the out years.  Additionally, the DCC should request not more than $2 million per year in Years 02 through 05 in the patient care category for the distribution of approved protocols.  The final amount will be determined by NICHD.  These funds will be managed by the DCC and distributed to each participating clinical site as a fee for service arrangement after a protocol has been approved and the NICHD has released the funds for distribution. 

The budget justification for each year must include a table that apportions the total cost request among the following categories:  1) core costs, 2) protocol initiation costs (per protocol), and 3) protocol support costs (per protocol).  Core costs should include support for essential personnel, information technology costs, committee management expenses and travel.  Protocol initiation costs should include the costs of preparing and/or expanding the protocol manual, developing data forms and questionnaires, recruitment materials and database structures.  Protocol support costs should include pharmaceutical handling, data entry and analysis, quality control, and manuscript preparation.  The total first year budget request should provide for the organization of all administrative aspects of the RMN and for the development of at least one protocol.  Budget requests for the out years should assume that additional protocols will be initiated and that one to two will be active during the grant period.  Costs for financial administration to prepare protocol budgets and to distribute and monitor funds should also be addressed.  The funds released for DCC operations in each year will be based, in part, on the number of protocols actually executed by the Network and may be more or less than the budget requested in the application.

Intent to Participate:

The RMN will be a collaborative effort that will require frequent interaction of awardees among themselves and the NICHD. Applicants must explicitly indicate their willingness to: participate in Steering Committee meetings (see Section VI, 2A, Cooperative Agreement Terms and Conditions of Award) and regular telephone conference calls; cooperate with other awardees in the development and design of research protocols; abide by common definitions, common methods for patient selection and enrollment, and common protocols, procedures, tests, as chosen by majority vote of the Steering Committee; comply with data reporting procedures and timelines as established by the Steering Committee and the DCC; comply with study policies and quality assurance measures approved by the Steering Committee; agree to oversight of the study by a Data and Safety Monitoring Committee (DSMC); report all adverse events in accordance with procedures established by the Steering Committee and NIH policies; and cooperate with other awardees in the publication of study results

Clinical Sites

The NICHD invites applications from both current members of the RMN (competing continuation applications) and from prospective members (new applications).

Scope:

The RMN clinical sites are responsible for the identification of priority areas for research, with input from the Steering Committee, the Advisory Board and NICHD staff; developing and implementing the Network protocols, recruitment and enrollment of subjects into approved protocols; collection and transmission of data to the DCC; and analysis of the data and timely publication of the results in peer-reviewed journals.

Minimum Requirements:

a) Principal Investigator: The named Principal Investigator (PI) must be a physician with clinical expertise related to reproductive medicine in women and/or men with a demonstrated access to an appropriate patient population and ability to recruit successfully to clinical studies. In addition to the named PI, the applicant must name at least two co-investigators. One of the co-investigators must be a doctoral-level biostatistician or epidemiologist. The other co-investigator must possess clinical expertise in reproductive medicine for the gender opposite that of the Principal -Investigator. For example, if the named PI specializes in gynecology, the co-investigator must specialize in clinical studies of the male (andrology, urology, internal medicine, etc.). The PI must devote at least 20 percent effort to the project, the biostatistical co-investigator must devote at least 10 percent effort, and the third investigator must devote at least 10 percent effort.

b) Institutional Environment: The applicant must have a history of previous successful clinical research and expertise in research design, biostatistics, and the development of clinical protocols. The ability to enroll sufficient numbers of patients for clinical studies should be documented. The applicant must be able to demonstrate past and existing excellence in collecting and maintaining clinical data on its patients. There must be firm institutional and departmental commitments to support this cooperative program and a strong staff dedication to adhere to programs jointly defined and to generate data of high quality. Applications from institutions that have a General Clinical Research Center (GCRC) funded by the National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application.

c) Other Staff and Facilities: An experienced research nurse must be designated as a full-time nurse coordinator and additional research nursing staff should be available. Laboratory facilities must be available for appropriate testing of patients and subjects, in such areas as hematology, blood chemistry, endocrinology, microbiology, radioimmunoassay and semen analysis. Appropriate imaging services must be available, including ultrasound, contrast studies, and other radiological and related techniques that may be required to diagnose and follow the conditions under study.

d) Concept Protocol: All applicants, competing continuation and new, will submit a concept protocol to provide reviewers and NICHD an idea of the capabilities of the applicant.  The concept protocol should describe one study, including background and significance, objectives, study design, and data analysis (including considerations of sample size, power and statistical model).  The protocol should estimate numbers of subjects potentially eligible at the applicant’s institution and should address the inclusion of women, minorities, and children as subjects.  The concept protocol will be limited to ten pages and must summarize a project that could potentially be undertaken by the RMN.  Therefore, the concept should necessitate a multi-center approach.   

e) Department and Institutional Commitments: There should be evidence of strong institutional support for the clinical site, including adequate space in which to conduct clinical activities and office space for staff. The department and institution must clearly support the cooperative nature of the program, including the capitated funding plan. These commitments should be clearly documented by providing letters to the Principal Investigator.

f) Access to Adequate Patient Population: The applicant must document the numbers of patients seen annually for reproductive health diagnoses, broken down by diagnosis in a tabular format. The applicant should describe the demographics of the population from which they expect to recruit their clinical subjects and plans for recruitment of women, minorities, and children. The applicant should include a brief discussion of previous relevant efforts and their specific plans for recruitment and retention of research subjects.

g) New Applications:  Prospective applicants must address their recent experience and participation in randomized clinical trails and other studies, preferably of a cooperative, multi-site nature.  Specific roles should be described for each study and research presentations and publications should be listed.

h) Competing Continuation Applications: Competing continuation applications should describe the site’s participation and contribution to the Network in detail, including subject enrollment in all studies, involvement in protocol development and their particular contribution to each study (e.g., Principal Investigator at site, participation on protocol and manuscript committees), collaborative Network activities, research presentations and publications.      

Budget:

Assurance of cooperation with the policy for capitation of research costs for each individual protocol, in addition to a base budget, should be provided.  In addition, the applicant should provide assurance of cooperation with the DCC for appropriate monitoring of enrollment to receive per-protocol funds.  The appropriate Federal cost policies and regulation governing NIH grant programs will be applied (see NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm

Each applicant will prepare a first year base budget based on the following:

Base budget costs are limited to $200,000 per year.  For out-year budgets, assume an annual increase of base salary and travel costs not to exceed three percent. 

On going annual budgets for the RMN clinical sites will be based on individual protocols as approved by the Steering Committee based on a capitation system.  Each RMN clinical site will be awarded base costs as described above in addition to funding from the Data Coordinating Center that represents per protocol costs, i.e. a flat fee for each subject successfully enrolled and completed for each study.  For sites with GCRC funding, applicable capitation funds can be reduced relative to the amount of GCRC support.  The Principal Investigator will be required to project subject enrollment for each specific protocol during a specified time frame, although continuation and the level of funding will be based on actual enrollment.   

Intent to Participate:

The RMN will be a collaborative effort that will require frequent interaction of awardees among themselves and the NICHD. Applicants must explicitly indicate their willingness to: participate in Steering Committee meetings (see Section VI, 2A, Cooperative Agreement Terms and Conditions of Award) and regular telephone conference calls; cooperate with other awardees in the development and design of research protocols; abide by common definitions, common methods for patient selection and enrollment, and common protocols, procedures, tests, as chosen by majority vote of the Steering Committee; comply with data reporting procedures and timelines as established by the Steering committee and the DCC; comply with study policies and quality assurance measures approved by the Steering Committee; agree to oversight of the study by a Data and Safety Monitoring Committee (DSMC); report all adverse events in accordance with procedures established by the Steering Committee and NIH policies; and cooperate with other awardees in the publication of study results

Pre-application Workshop

An information pre-application workshop addressing the scientific and administrative issues associated with this initiative will be held on March 23, 2006 in association with the Society for Gynecological Research meeting in Toronto, Canada.  The purpose of this workshop is to familiarize the potential applicants with established NIH guidelines and review criteria; discuss the areas of NICHD programmatic emphasis; and facilitate the submission of a well-organized application.

Potential applicants should contact Dr. Tracy Rankin to request further details.  Individuals planning to attend are requested to submit specific questions to Dr. Rankin at least one week in advance of the workshop.  Attendance at the workshop is not required to submit an application in response to this solicitation.  A summary of the workshop will be posted at http://www.nichd.nih.gov/about/cpr/rs/workshops.htm.

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

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

The scope and variety of the research strengths of the proposals to enable a successful collaborative program will also be considered.  Final selection of the Clinical Sites for funding may be partly based on the need for diversity, including geography and special populations. 

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 NICHD in accordance with the review criteria stated below.

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

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 the following outlined 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. 

Data Coordinating Center (DCC) Applicants

In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals in the context of serving as the DCC for the Reproductive Medicine Network:

1)    Experience and ability in multi-center, collaborative clinical trials:  documentation of expertise in protocol development, staff training, research instrument development, data management, biostatistical expertise as applied to study design, data administration and coordination.

2)    Plan for implementing protocols and procedures:  demonstration of expertise in manual of operations development, data collection and management, quality assurance, randomization, data analysis and human subjects protections.  Also the experience and expertise of the investigator in development of site-monitoring plans, safety monitoring plans, in FDA regulatory requirements pertaining to IND applications and Good Clinical Practice compliance.

3)    Staff experience and capability:  scientific and administrative abilities of the Principal Investigator and other team members; experience of the Principal Investigator and key personnel in statistics, data management, quality control, study coordination and administration of multi-center clinical trials.

4)    Environment:  demonstration of adequate resources, including staffing, and institutional support to support participation in a collaborative program.

5)    Competing continuation applicant:  evidence of successful past performance as a Data Coordinating Center, addressing points one through four above in this context.  Specifically, reviewers will be asked to comment on the centers performance in providing statistical leadership, protocol development, safety monitoring plans for executed protocols, site management, data management, and publication record. 

Clinical Site Applicants

In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals in the context of serving as a Clinical Site for the Reproductive Medicine Network:

1)    Qualifications and experience of the principal investigator, co-investigator and staff:  the expertise, training and experience of the Principal investigator and the research team in the conduct of clinical trials, particularly cooperative, randomized clinical trials; commitment of staff time for the satisfactory conduct of Network activities; experience and qualifications of team members responsible for subject recruitment, enrollment, data collection and data management; knowledge and experience of the investigators in areas relevant to reproductive medicine

2)    Institutional environment:  adequacy of institutional resources including personnel, space, administrative support (fiscal management support, personnel management, procurement and budgeting)

3)    Concept protocol:  evaluation of the proposed protocol in terms of quality and relevancy of proposed hypotheses, background and significance, objectives, study design, and data analysis (including considerations of sample size, power and statistical model).

4)    Patient access and study population:  plans for recruitment and retention of subjects; plans to ensure appropriate representation by ethnicity, age and gender

5)    Department and institutional commitment:  willingness and ability to participate in the Network, including applicant institution’s history of collaborative research, depth of commitment, willingness to randomize subjects, and ability to work with other Network sites

6)    Competing continuation applications:  evidence of successful past performance as a clinical site in the Reproductive Medicine Network.  Reviewers will be asked to comment on the re-competing sites’ effectiveness at:  protocol development, including concept development and research design; site performance in past and current clinical trials, including successful subject recruitment, data quality, and subject follow-up; presentation and publication record; and cooperation in a multi-center network.  Additionally, the reviewers should comment on the effectiveness of the Principal Investigator in providing site leadership and cooperating with all aspects of the RMN.

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).

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 (NIH Cooperative Clinical Research for Clinical Sites [U10]), 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 above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for identifying priority areas for research, with input from the Steering Committee, the Advisory Board and NICHD staff; developing and implementing protocols; recruiting and enrolling subjects into approved protocols; collecting and transmitting data to the DCC; and analyzing the data and publishing the findings of the RMN.  The awardee will agree to accept the participatory and cooperative nature of the RMN Network. The Principal Investigator and co-Investigators will be members of the Steering Committee and will be required to participate in all Steering Committee activities and to follow the policies and procedures that are developed by the Steering Committee. Each RMN clinical site will have one vote in all Steering Committee matters. The clinical site PIs will be required to provide primary study data to the DCC for management, quality control and analysis.

The DCC will provide statistical leadership for the Network through developing study designs and analyses; establishing a collaborative database and data management procedures; establishing site monitoring plans; assuring compliance with all regulatory requirements in conjunction with NICHD staff; providing procedures for data analysis, reporting and publication; providing procedures for the submission of copies of the collaborative data sets to each Principal Investigator and the NICHD upon completion of the study; and providing procedures to protect and ensure the privacy of medical and genetic data and records of individuals.

The Data Coordinating Center (DCC) will provide a broad range of support services to the RMN in accomplishing its goal. It will serve to centralize and standardize the data that are derived from collaborative studies and will put the data sets into a common format that will facilitate their use by RMN member projects. The DCC will also serve as a collaborative member of the RMN by assisting in the statistical planning and implementation of clinical protocols and by providing logistical services to the RMN members as required by the multi-center research program. The DCC will assist with the preparation of Data and Safety Monitoring Committee (DSMC) reports, scientific manuscripts and other reports and documents as needed to support the goals of the RMN clinical sites.

Specifically, the DCC will  assist with protocol and manual of operations development; develop a data and safety monitoring plan for each implemented protocol; develop and implement a plan for adverse event reporting in coordination with NICHD staff; perform interim analyses of safety and efficacy for the Data and Safety Monitoring Committee, NICHD and the Steering Committee; conduct final analyses and participate on publication writing teams; produce study monitoring reports for the Steering Committee and NICHD; and conduct analyses and summaries of annual and interim reports for NICHD-sponsored Investigational New Drug Applications (IND) in cooperation with NICHD staff.  Additionally, the DCC will serve as a data archive to preserve the data for future secondary analyses and for access by the outside community.

The DCC will also provide central registration and randomization for all study subjects as required by study protocols; develop case report forms and standardized criteria for clinical endpoint verification; design and implement systems for the efficient tracking and transfer of clinical and laboratory data to the central database; provide data management training to the clinical sites; provide for central storage, security, processing and retrieval of study results; and prepare selected public access databases. The DCC will initiate, monitor and close out clinical sites to assure Good Clinical/Laboratory Practice; audit clinical sites and provide reports to the NICHD and the Steering Committee.  The DCC will work with NICHD staff by providing them with clinical study data, reports, and other support as required for Adverse Event Reporting and IND submissions

The DCC awardee will agree to accept the participatory and cooperative nature of the RMN Network.  The Principal Investigator of the DCC will have one vote on the Steering Committee.  All activities of the DCC must be closely coordinated with the Steering Committee.

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.

2.A.2. NIH Responsibilities

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

The NICHD Project Scientist will have substantial scientific/programmatic involvement during the conduct of the Network through technical assistance, advice and coordination above and beyond normal program stewardship for grants. The NICHD Project Scientist will participate by reviewing and commenting on each stage of the program before implementation; by advising in management and technical performance; by advising in the acquisition of needed resources (e.g. drug supplies, tissue bank repositories); and by participating in the preparation of publications. The Project Scientist will serve as the liaison/facilitator between the awardee, pharmaceutical industries and other government agencies (e.g. FDA) and will serve as a resource of scientific and policy information related to the goals of the awardee.

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.

2.A.3. Collaborative Responsibilities

Steering Committee

The primary governing body of the RMN will be the Steering Committee. The Steering Committee will be composed of the following: the Principal Investigators of the clinical sites; the named co-Investigators of each clinical site; the Principal Investigator of the RMN DCC; the NICHD Project Scientist; and an independent Committee Chair named by the NICHD. All major scientific decisions will be determined by the Steering Committee with each clinical site having one shared vote and all other members of the Steering Committee having one vote.

The Steering Committee will review all concepts for scientific merit and feasibility; review all protocols prior to implementation; review all public presentations of the RMN results and manuscripts, posters, and abstracts prior to publication; review compliance with protocol requirements; define subcommittees; develop Network and study policies; receive and act upon reports of subcommittees, the Advisory Board and the DSMC; and review matters relevant to administrative, financial and medical considerations of studies.

The Committee Chairperson is responsible for the overall administration of the Steering Committee and provides leadership for all activities described above. The Chairperson, together with the NICHD Project Scientist, schedule Steering Committee meetings; establish an agenda for those meetings and monitor the work of subcommittees.

The NICHD Project Scientist will convene the first meeting of the Steering Committee. Thereafter, the Committee will meet in person or by teleconference at least four times a year. The Chairperson and NICHD Project Scientist will schedule additional meetings by teleconference as necessary and as determined.

The Committee will have primary responsibility for developing the common clinical protocols. One Principal Investigator or subcommittee will take the lead responsibility for drafting each individual protocol, with the assistance of the RMN DCC and NICHD Project Scientist.

The Steering Committee will provide input and will be responsible for oversight of protocol development. The decision to implement the protocol will be determined by a vote of the entire Steering Committee and will be subject to additional review by the DSMC.

The Steering Committee, or a subcommittee, will review the budget and expenditures at least once each year at a face-to-face meeting. Clinical trials will proceed into the implementation stage only with the concurrence of both the Steering Committee and the NICHD Program Official. Each Steering Committee member will be expected to participate in all Steering Committee activities--e.g., meetings, conference calls, subcommittee activities, etc…, as necessary.

The Steering Committee, or a subcommittee, will develop a set of criteria for assessing the performance of the participating institutions with particular attention to accrual of adequate numbers of subjects, timely submission and quality of required data and conscientious observance of protocol requirements. The Committee, or the designated subcommittee, will prepare an annual report containing information on the progress in ongoing and newly-initiated clinical trials; subject accrual and protocol compliance at all participating sites; manuscripts published, in press, and in preparation; presentations at scientific meetings; and budget review. The DCC will take the lead in writing this report; the NICHD Project Scientist will not participate substantively in the production of this report and the Committee Chairperson, the RMN Advisory Board and the NICHD Program Official will be responsible for reviewing the report for NICHD.

Advisory Board

An Advisory Board, convened by the NICHD, will advise the Steering Committee in the identification and prioritization of topics and protocols for the RMN. The Advisory Board will be composed of senior scientists, not part of the Network, with expertise in obstetrics and gynecology, andrology, biostatistics, epidemiology, human genetics and clinical trial design. The Chairperson of the Steering Committee and the NICHD Project Scientist will serve as ex officio members of the Advisory Board. Additional members will participate as necessary for specific expertise.

Data and Safety Monitoring Committee

A Data and Safety Monitoring Committee will monitor the safety of ongoing clinical trials and advise on their conduct. This committee will be established by NICHD and consist of individuals with expertise in obstetrics and gynecology, andrology, biostatistics, epidemiology, population genetics, clinical trial design and ethics. This committee will focus on safety, ethics, and scientific and statistical integrity of both proposed and ongoing trials.

Data Coordination and Management

The RMN DCC will carry out data coordination and management.  As described, each participating clinical site will be responsible for providing primary study data to the DCC for management, quality control and analysis. Specific analyses to be performed will be directed by the Steering Committee. The results of those analyses will be delivered to the Steering Committee and the Steering Committee is responsible for determining how the results are interpreted, whether the results should influence ongoing data collection, and how the findings should be disseminated. All participating sites will have access to all data originating from their sites.

Publication and Presentation

Timely publication of findings is required. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgement of the participating institutions and NICHD support. Review and approval by the Steering Committee will be required for all analyses prior to publication or presentation according to criteria that will be developed by the Steering Committee.

Collaboration with the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR)

The Principal Investigators of the clinical sites and the DCC will be required to attend the annual SCCPIR research meeting.  The purpose of this meeting is to familiarize the Network investigators to the latest developments in basic investigations in reproductive science and thereby facilitate translational development.  Additionally, the Network will be expected to present their latest research findings to the SCCPIR investigators at this same annual meeting.  For some proposed studies, certain SCCPIR sites may be provided the resources to serve as additional recruitment sites for RMN initiated protocols.

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:

Tracy L. Rankin, Ph.D.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B-01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)  

Telephone: (301) 435-6979
FAX:  (301) 480-2389:
Email:  rankint@mail.nih.gov

Lisa Begg, Dr. Ph.H., R.N.
Office of Research on Women’s Health
Office of the NIH Director
1 Center Drive, Room 201, MSC 0161
Bethesda, MD  20892-0161
Telephone: (301) 496-7853
FAX: (301) 402-1798
Email:  beggl@od.nih.gov  

2. Peer Review Contacts:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510 
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)  

Telephone: (301) 496-1485
FAX: (301) 402-4104
Email:  stretchr@mail.nih.gov  

3. Financial or Grants Management Contacts:

Cecilia Bruce
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)  

Telephone: (301) 496-1304
FAX: (301) 451-5510
Email: brucec@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.

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/ 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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