Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This funding opportunity announcement (FOA) invites applications from institutions/organizations willing to participate with the NICHD in an ongoing multi-center clinical program designed to study clinical and health aspects of pelvic floor disorders in women. Pelvic floor disorders for the purpose of this FOA include urinary incontinence, fecal incontinence, pelvic organ prolapse, and other sensory and emptying abnormalities of the lower urinary and gastrointestinal tracts. Clinical and health aspects of pelvic floor disorders include surgical and nonsurgical treatments, pharmacologic therapies, social and behavioral interventions, outcome analysis for the broad array of treatments available, and prevention efforts, among others. Importance is also placed on the inclusion of innovative translational aims which maximize the use of well-defined study populations in order to contribute to the understanding of the etiology and pathophysiology of these disorders.

The overall objective of the Pelvic Floor Disorders Network (PFDN) is to facilitate interactions between a network of academic centers with the recruitment capabilities and research expertise needed to perform studies under rigorous common protocols that will provide evidence-based clinical answers to both providers and women more rapidly than would otherwise be possible for an individual clinical research center.

The infrastructure is organized to allow for randomized double-blinded placebo controlled trials followed by the analysis of both short-term and long-term outcome measures. The infrastructure also allows for observational studies, particularly those that will inform the development of randomized trials. In addition, translational aims have begun to be incorporated into the most recent PFDN studies. It is anticipated that 6 -8 Clinical Sites will be involved in the program, along with one Data Coordinating Center.

The PFDN was established by the NICHD in 2001 in response to an increasing awareness by the public and by health professionals of the need for more evidence-based data to guide both surgical and non-surgical clinical care for pelvic floor disorders. The public health impact of pelvic floor disorders is large and growing. The National Health and Nutrition Examination Survey (NHANES) estimates that these disorders affect almost one-quarter of women between the ages of 20 and 80 and projects that up to 58 million women will have at least one pelvic floor disorder in 2050; 41 million with urinary incontinence, 25 million with fecal incontinence, and 9 million with pelvic organ prolapse. The national burden related to pelvic floor disorders is large in terms of direct health care costs, lost productivity, and decreased quality of life as affected individuals may withdraw from their social lives and incontinence may be a major factor requiring nursing home care in the elderly.

In many cases, clinicians caring for women with pelvic floor disorders have adopted principles of care and both surgical and non-surgical techniques before rigorous, controlled evaluation has taken place. A lack of data on failure rates, complications, and cost effectiveness of therapies contributes to both the financial burden and the inability of providers and patients to make well informed treatment decisions. High quality clinical outcome data for fecal incontinence is particularly scarce as fecal incontinence is often not reported due to social stigma. Regional and international differences in surgical practice without strong scientific justification have also complicated the development of treatment guidelines.

It is clear that pelvic floor disorders are a source of substantial morbidity for women and thus represent a health care issue which requires expert knowledge obtained through evidence-based research which addresses the prevention, diagnosis, pathophysiology and treatment of these disorders. The NICHD established the PFDN to support a multicenter network in response to the need for high quality clinical trials in this program area. Studies include both careful analysis of standard treatment outcomes as well as testing new therapies and approaches to move the research agenda forward in novel directions for clinical benefit.

The PFDN objectives continue to focus on a robust research agenda which designs and executes high quality randomized trials and translational studies to benefit women with pelvic floor disorders. Historically, the PFDN has completed approximately 5 large studies per cycle. Seven Clinical Sites and a Data Coordinating Center were selected for the first 5 year cycle (2001-2006). Some of the studies initiated in the first cycle were: 1) a randomized trial on the risks and benefits of adding Burch colposuspension to abdominal sacral colpoplexy for prevention of stress urinary incontinence in women with prolapse but without baseline stress incontinence symptoms; 2) a cohort study of the prevalence and incidence of pelvic floor symptoms in postpartum women after vaginal delivery with and without anal sphincter laceration compared to cesarean delivery without labor; 3) a cohort study of colpocleisis; and 4) development and validation of an instrument to assess the use of adaptive behaviors in women with pelvic floor disorders. In the second 5 year cycle of the PFDN (2006-2011), the following studies were initiated: 1) a randomized clinical trial with a patient preference arm to determine whether symptom-specific treatment of urinary incontinence after prolapse surgery is equally effective to prophylaxis by adding Tension-free Vaginal Tape mid-urethral sling at the time of prolapse surgery; 2) a randomized clinical trial to compare surgical outcomes between sacrospinous ligament fixation and uterosacral vaginal vault ligament suspension which included a study on the impact of perioperative behavioral therapy/pelvic muscle training in women undergoing vaginal surgery; 3) a randomized clinical trial to compare the prevalence of fecal incontinence in women who have sustained an obstetric sphincter laceration who receive either usual care or a behavioral intervention; and 4) a double-blind randomized trial comparing the change in urge incontinence episodes between women receiving intra-detrusor Botox A injections and anticholinergic therapy.

In the current and third cycle of the PFDN (2011-current), with 8 funded clinical sites, study enrollment was completed on 3 studies at the time of this FOA: 1) a random assignment of Interstim compared to Botox A injections in the bladder for the treatment of refractory urge urinary incontinence; 2) a randomized trial comparing uterosacral ligament suspension and hysterectomy to hysteropexy with the Uphold LITE vaginal support system; 3) randomly assigning participants with mixed urinary incontinence already proceeding with a sling procedure to a standardized behavioral/physical therapy program or to regular follow up care. Large translational aims in the third cycle have included: 1) characterization and evaluation of the impact of 2 different treatment modalities (Interstim and Botox A ) for refractory urgency urinary incontinence on bladder inflammation and tissue remodeling manifested via biomarkers present in urine; 2) comparison of the urinary microbiome in women with mixed urinary incontinence with unaffected controls; 3) comparison of the baseline proportional levels of butyrate and other metabolites in stool samples of women with fecal incontinence relative to unaffected age-matched controls; and 4) qualitative work to develop a new patient reported outcome measure for anal incontinence.

Studies not completed at the time of this FOA are 1) a factorial design investigating improvement in fecal incontinence with loperamide versus placebo and/or usual care versus standardized anal sphincter training with manometry-assisted biofeedback, and 2) a three arm apical suspension trial for post-hysterectomy vault prolapse using sacral colpopexy, transvaginal mesh and native tissue apical repair. These and other studies may be continuing to enroll subjects at the initiation of the next award period beginning April 2016. The NICHD intends to enable the PFDN to initiate new protocols within the first year of the next award period in addition to completing studies in progress at the end of the current cycle. Clinical Sites selected to join the PFDN should be prepared to participate in ongoing protocols unless otherwise directed by the Steering Committee. New protocols will be decided cooperatively by the Steering Committee, with advice from the Advisory Board. A Data Safety and Monitoring Board reviews all protocols before initiation and also advises NICHD on research design issues, data quality and analysis, and ethical and human subject protection matters.

The scope of research of this FOA includes clinical problems in urinary incontinence, fecal incontinence, and pelvic organ prolapse and other sensory and emptying abnormalities of the lower urinary and gastrointestinal tract. Randomized trials are the preferred approach although other experimental approaches can be considered, especially as required to address translational objectives or the development and validation of quality of life instruments and measures which will inform subsequent randomized controlled trials. In all cases, good use of the multicenter capabilities and the collaborative process is paramount.

Because treatment of pelvic floor disorders is markedly different in men and children compared to women, participation in the clinical protocols planned under this initiative are restricted to adult women.

Examples of research topics which may be proposed include, but are not limited to:

• Comparative effectiveness research on surgical treatments, pharmacologic agents, devices, and other non-surgical treatments including behavioral therapies;
• Primary prevention studies;
• Postoperative management strategies to minimize recovery time and recurrence of pelvic floordisorders;
• Studies investigating the optimal timing of interventions;
• Studies that address complications and failures from interventions for pelvic floor disorders;
• Innovative research exploring new therapies utilizing findings from laboratory research in areas that could include, as examples, fecal transplants or pharmacogenetics;
• Translational studies using human samples to investigate the etiology of pelvic organ prolapse, urinary incontinence or fecal incontinence, including the role of the microbiome and metabolome.

The Pelvic Floor Disorders Network Clinical Sites will be a collaborative network of up to nine Clinical Sites, one Data Coordinating Center (DCC), and the NICHD. The DCC is supported by a separate award, described in detail in RFA-HD-16-011. Clinical Sites will be responsible for proposing protocols that are appropriate and feasible for adoption by the Network, guiding protocol development, enrolling patients, analyzing results, and disseminating research findings. All Clinical Sites will be required to participate in a cooperative and interactive manner with one another, the NICHD and the DCC.

A Steering Committee will be the main governing body of the Network and will be composed of the PDs/PIs of the Clinical Sites and the Data Coordinating Center and the NICHD Project Scientist. At the discretion of the NICHD, a Network Steering Committee Chairperson may be appointed and non-voting members from other NIH Institutes and Offices may be present. The structure and role of the Steering Committee are described below under Cooperative Agreement Terms and Conditions of Award.

Research topics of high priority are identified by the Steering Committee with input from the Advisory Board, and lead to the design and implementation of protocols appropriate for the evaluation, diagnosis, prevention, and management of pelvic floor disorders.

A centralized DCC supports the activities of the Network. The functions of the DCC include developing protocol data management, devising novel comparative study designs, providing sample size calculations and statistical advice, developing data forms and protocol tools, performing data analyses, coordinating the activities of the Steering Committee, Protocol Review Committee, Advisory Board and Data and Safety Monitoring Board, and overall study coordination and quality assurance.

In addition, in order to hasten accrual in Network studies, at the discretion of the vote of the Steering Committee (see below), the DCC, along with the NICHD and the Clinical Site PDs/PIs, will have the responsibility of identifying qualified and interested investigators at non-Network sites who wish to enroll patients in these studies. Arrangements for data collection and reimbursement of trial-related data collection costs at non-Network sites will be the responsibility of the DCC.

An External Advisory Board will meet in person biennially and by teleconference or webinar at least 3 times per year.

A Data and Safety Monitoring Board (DSMB) will monitor Network interventional studies. As a part of its monitoring responsibility, the DSMB will submit recommendations regarding the continuation of each study in its purview to the DCC which will be used by PD(s)/PI(s) to provide information to their institutional review boards (IRBs). Funding for the functioning of the DSMB and the External Advisory Board will be provided through the base funds of the DCC.

Participation in Studies

As per the intent of the NICHD in supporting this network, multiple trials and descriptive studies will be conducted during the five-year project period. It is anticipated that initially one study may be selected from the studies proposed by the successful applicants. However, a decision to fund a particular Clinical Site will not commit the Network to develop or pursue the study protocol proposed by that Site. Nevertheless, awardees must agree to actively enroll patients in at least one Clinical Network trial and/or descriptive study in the first year of the award. Applicants should plan that, after the first year, at least three studies will be enrolling patients each year.

It is anticipated that each protocol will be implemented in all of the Clinical Sites. As specific protocols are developed, support will depend on the availability of funds, and per patient (capitation) funding made available. All the Clinical Sites must be willing to pursue this funding arrangement for each new protocol conducted. Clinical Sites that do not enroll patients in PFDN protocols or do not collaborate in the scientific development activities of the PFDN may not receive continuing support at the discretion of the Program Officer. Clinical protocols must be approved by local IRBs, and Clinical Sites will be supported in this effort by the PFDN DCC.

The exact number of protocols supported in the five-year program will depend on the nature and extent of the investigations proposed by the Steering Committee and on available funds. Both short-and-long term projects will be considered for prioritization and implementation.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

The PD(s)/PI(s) for a Clinical Site should be able to demonstrate the ability to treat urinary incontinence, fecal incontinence, and pelvic organ prolapse as well as other pelvic floor disorders both surgically and nonsurgically. Typically the PD(s)/PI(s) would be urogynecologists or urologists with board specialization in Female Pelvic Medicine and Reconstruction Surgery, but other types of physicians/surgeons are eligible if they can demonstrate this expertise.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Lisa Halvorson, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-1646
Email: lisa.halvorson@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: A detailed description of the clinical attributes of the Clinical Site must be provided.  This should include imaging and diagnostic testing available for women with pelvic floor disorders.  This may include, but is not limited to, multichannel and fluoroscopic urodynamic testing, ultrasound (specify endoanal, perineal, etc.), both dynamic and traditional MRI, and defecography. Any other unique technologies to the site should be described. Available space for performing Network-related activities should be described.  The availability of a pharmacy capable of supporting clinical research must be documented and details on experience in preparation, administration, and storage of masked pharmaceuticals should be included. The Clinical Site should also describe the ability to collect and handle laboratory specimens.

Population Available for Clinical Research 

The nature of the patient population available for clinical research must be clearly defined.  In order to provide peer reviewers with the relevant characteristics of the specific patient population available for study at the applicant Clinical Site, include information regarding admissions over the designated two year period of January 1, 2013, to January 1, 2015.  This information should include the number of inpatients and outpatients (presented separately) treated for pelvic floor disorders.  Separate tallies should be presented for: 1) pelvic organ prolapse; 2) urinary incontinence and other relevant lower urinary tract disorders; 3) fecal incontinence and other relevant lower gastrointestinal tract disorders; and 4) other pelvic floor disorder treatments specified by the Clinical Site.  For applicants with more than one Clinical Site, please include each Consortium Site's information in a clearly identified separate section.  If there are ongoing or pending studies/trials that will limit availability of patients for PFDN trials, these must be described for the review panel's consideration at the time of review.

All instructions in the SF424 (R&R) Application Guide must be followed.

The PD/PI should be a practicing physician able to care for all types of female pelvic floor disorders.  One other investigator should be designated as the Alternate PD/PI who is able to serve in the absence of the PD/PI. The Alternate PD/PI may be one of the named PD(s)/PI(s) on a multiple PD/PI application. Overall, there must be at least three full time, academically oriented clinician investigator specialists in female pelvic floor disorders at each Clinical Site. At a minimum, this includes the PD/PI and at least two other investigators in specialties such as urogynecology, urology, gynecology, colorectal surgery, gastroenterology, geriatrics, radiology, and physical or occupational therapy.  The biosketches of the PD(s)/PI(s) and other investigators should describe academic and clinical qualifications as well as current and planned clinical, research, administrative, and academic commitments. A complete description of the investigator’s training and qualifications in clinical care and research is required, including experience in research design and implementation of collaborative clinical research especially randomized clinical trials. 

All instructions in the SF424 (R&R) Application Guide must be followed.

A Base Budget estimate for the Clinical Site should be included for all years. The first year Base Budget will be limited to $180,000 in direct costs with allowances as follows:

• Contact PD/PI: minimum 15 percent (1.8 person months) effort
• Alternate PD/PI: minimum 10 percent (1.2 person months) effort
• Research Nurse Coordinator: minimum 80 percent (9.6 person months) effort
• Travel: a total of four quarterly, 2-day meetings per year; 2 meetings to the Washington D.C. area and 2 meetings at Clinical Site locations (generally one on the West Coast and one in the Central US). Funds should be budgeted to provide travel for the PD(s)/PI(s), Alternate PD/PI, and Research Nurse Coordinator. The PD(s)/PI(s) should make a commitment to attend all Steering Committee meetings.

When a Clinical site application has been favorably recommended and is being considered for funding, the applicant will be required to accept capitated protocol budgets for those studies underway in the Network, and participate in planning protocol budgets for studies under development. For additional information, please see Section VI. Award Administration Information.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Include Specific Aims for the Clinical Site application.

Research Strategy: The Research Strategy section should address all of the following issues:

• Describe relevant experience of the clinical site with previous or ongoing clinical trials, especially those of a cooperative or multicenter design, in the field of women's reproductive health or pelvic floor disorders. Contributions in key areas of research development and design, patient recruitment, retention and study completion, data collection and analysis, as well as a track record of publications should be described in the application.
• Clinical sites that are current PFDN members should describe their participation and contribution to the Network in detail including patient enrollment in studies, involvement in trials, specific contributions to each trial (e.g., PD/PI at clinical site, protocol committee member), subcommittee activities and publications. 
• New applicants must describe their recent experience and participation in randomized clinical trials, preferably of a multicenter nature.  Specific roles and activities (e.g., PD/PI, participating site, steering committee, writing committee, trial design and development) should be described for each study.  Publications should be listed that resulted from participation in studies.

For the proposed project period, describe plans for recruitment and retention of subjects.

• Staffing and Management Plans: The application should describe strategies and plans for staffing and managing clinical site functions. The time commitment of each funded investigator will vary depending on the specific Network protocols ongoing at any particular time and the Clinical Site should have the ability to add or remove investigators as appropriate.
• A research nurse coordinator or personnel with research training and experience in multiple clinical trials must be designated to coordinate day to day activities of the site. Additional research support staff should be available, as protocols may require patient recruitment at night or on weekends.  Staff training and roles in clinical research and randomized clinical trials should be described in the application. The ability to have sufficient research staff to mask some staff for certain trials should be noted. Plans and procedures for quality information transfer to the Data Coordinating Center should be described.
• Clinical Sites that propose to combine institutions or multiple sites must describe and justify the proposed organization and provide a detailed logistical plan for collaboration and cost-effective management. The history of the multi-site relationship should be described including eligibility and enrollment in previous clinical trials.
• Special Strengths of the Institution: Applicants are encouraged to describe special or unique strengths of the site that may be relevant to female pelvic floor disorders research.  This can include state-of-the art scientific capabilities such as modern imaging techniques, proteomics, genomics, microanalysis, genetics, clinical pharmacogenetics, and surgical techniques which may be shared or may be available to develop and expand the scientific productivity of the Pelvic Floor Disorders Network.  Do not duplicate information described in Other Project Information, Facilities and Other Resources.

Letters of Support: Strong institutional commitment must be clearly documented with letters of support from appropriate individuals.  There must be a clearly expressed intent to participate in a collaborative manner with the other Clinical Sites, the Data Coordinating Center, and the NICHD.  Clinical Sites are expected to participate in all Network studies unless applicants describe implemented trials at their clinical site that conflict with ongoing Network studies described in this FOA as part of their application. Evidence of past support can also be cited.  Letters should describe support in areas of grants management, personnel management, space allocation, procurement, equipment as well as general support of the research. Letters supporting the research capabilities and activities of the Clinical Site should be included. Multi-site applications should have appropriate letters of support for the collaboration.  

Letters from the Service or Division Chairperson and the Chief Operating or Executive Officer of the facility where the applicant is based, must be included in the application.  These letters must indicate support for the application and clearly state that appropriate clinical time commitments and schedule modifications will be made as needed to assure the applicant and Clinical Site's full participation in Network studies, as well as writing and administrative responsibilities as part of the Steering Committee.  Assurance of cooperation with the policy for capitation of research costs for each individual protocol should also be provided from the departmental and institutional offices of sponsored research programs.

Applications from institutions that have a Clinical and Translational Science Award (CTSA) must describe the type and amount of support available from those resources for conducting research at the PFDN Clinical Site. Institutions with a CTSA should provide a letter from the program director that describes the level of support and gives specific examples of that support. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the scientific, administrative, clinical and academic qualifications of the PD/PI, the research team, and the Research Coordinator appropriate for the PFDN?  Do the key personnel have the knowledge and experience in areas relevant to the conduct of collaborative clinical research, including both randomized clinical trials and well-designed observational studies, with experience in research design and leadership?  Is the commitment of staff time satisfactory for the conduct of Network activities?  Do the team members responsible for subject recruitment, enrollment, data collection and data management have the necessary qualifications?  Is there evidence of the quality of the investigators' participation in randomized clinical trials or seminal observational and translational studies in the recent past?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Is there evidence that the Clinical Site will be a source of innovation in the scientific questions and design?

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Are appropriate populations available and is there evidence of commitment to prioritize PFDN studies?  Does the application demonstrate willingness to work and cooperate with other PFDN Clinical Sites and the NICHD?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there demonstrated willingness to work and cooperate with other PFDN Clinical Sites, the DCC and the NICHD? Is there demonstrated adequacy of administrative, clinical, and data organizational management facilities as described in the requirements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

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

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NICHD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development (NACHHD) Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Consideration of program balance; that is, the scope and variety of research strengths to enable a successful collaborative program. This will include contributions in ethnic diversity of subjects available for study, as well as diversity in PD/PI expertise.
• Relevant capabilities and experience to be used in executing the responsibilities of the Clinical Site.

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. 

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

When a Clinical site application has been favorably recommended and is being considered for funding, the applicant will be required to accept capitated protocol budgets for those studies underway in the Network, and participate in planning protocol budgets for studies under development.

NOTE: Ongoing funding of the Clinical Sites will be based on individual protocols that will be funded through a capitation system in addition to the annual base budget.  Capitation costs are a flat fee for each subject successfully enrolled and completed for each study.  Capitation costs are determined by estimating clinical study costs per subject by the Clinical Sites with approval for the final funding by the Steering Committee.  For Clinical Sites with CTSA support, capitation costs can be reduced relative to the amount of CTSA support. The Data Coordinating Center will be responsible for issuing per protocol payments to the Clinical Sites for each study based on enrollment and completion of indicated study visits and data collection points under the capitation system.

Each PFDN Clinical Site will be awarded base costs (as listed above) from the NICHD.  The Clinical Site's F&A rates on the initial competitive awards will not be increased in future years due to changes in their negotiated rate agreements.

Total funding for Clinical Sites depends on the base awards and reimbursements for approved protocol-related expenses from the DCC.  The overall provision of money for the PFDN is subject to the availability of NICHD funding.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Identification of priority areas for research.
• Developing and implementing the Network protocols.
• Collection and transmission of data to the DCC.
• Analysis of data and publication of results of PFDN studies.
• Accepting the collaborative nature and the role of the group process as cooperative and
• participatory.
• Projecting subject enrollment for specific protocols during a specified time frame (continuation and level of funding will be based on actual enrollment).
• Design and execution of PFDN studies, supervision of personnel, interaction with Institutional Review Boards, interaction with Clinical Site grants management officials, and for collaboration and cooperation with the other Clinical Site PI(s), the Steering Committee, NICHD, and the DCC.
• 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.

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

NICHD Project Scientist -- The NICHD Project Scientist will provide technical assistance and participate as one voting member of the Steering Committee.  Specifically, the NICHD Project Scientist will:

• Assist with the identification of important areas of study.
• Assist in the development of Network protocols.
• Assist in the development and review of capitation-based budgets, including the identification of
• study costs and special institutional needs.
• Assist in the review and evaluation of each stage of the program before subsequent stages are
• started, in conjunction with the Steering Committee, DSMB, NICHD Program Official (see below),
• and Advisory Board, and make recommendations to enhance the scientific quality of the work.
• Assist in the reporting of results to the community of investigators and health care recipients.
• Assist in the conduct of the trials and studies, including ongoing review of progress, possible
• redirection of activities to improve performance and cooperation, and frequent communication with other members of the Steering Committee.
• Participate on the Steering Committee and all active subcommittees.
• Liaison with Project Officer in regards to communication of progress and difficulties.

NICHD Program Official -- 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 Program Official, apart from the Project Scientist, will:

• Carry out continuous review of all activities to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines.
• Have the option to withhold support to a participating institution if technical performance
• requirements are not met, such as protocol compliance, enrollment targets, or randomization of
• subjects.
• Have the option to modify or terminate a study based on advice from the Steering Committee, the Data and Safety Monitoring Board, or the Advisory Board.
• Perform other duties required for normal program stewardship of grants.

Areas of Joint Responsibility include:

Steering Committee - The Steering Committee will be the main governing body of the PFDN and will have primary responsibility for developing research protocols by consensus, supervising the conduct of the studies, approval of study budgets, and the preparation of publications.  The Steering Committee will consist of the PD(s)/PI(s), the PD/PI of the DCC, and the NICHD Project Scientist.  Each full member will have one vote.  For multi-PI applications, the designated Contact PD/PI will be the voting member for that site. Other non-voting members from other Institutes and Centers may participate. An outside chairperson, who is not participating as an investigator, will be selected by the NICHD to serve as chair in creating the agendas and conducting the meetings. All major scientific decisions will be determined by super-majority vote of the Steering Committee.  Committees will be established by the Steering Committee, as deemed appropriate.  A member of the NICHD Grants Management Branch will advise the Steering Committee on funding matters.  The PFDN has established policies and procedures that govern its operations, including publications.  These policies and procedures can be amended by the Steering Committee and the NICHD.  Awardees will be required to accept and implement the common protocols, policies and procedures approved by the Steering Committee.

Advisory Board -- The Advisory Board assists the Steering Committee in the identification and prioritization of topics for research, mainly through review of protocols at the mid-development stage.  Members are appointed by the NICHD with input from the Steering Committee and their expertise can include clinical trial design, statistics, epidemiology, obstetrics and gynecology, urology, urogynecology, gastrointestinal disorders, and colorectal surgery.   The PD/PI of the Data Coordinating Center and the NICHD Project Scientist will attend Advisory Board Meetings as non-voting members.

Data Safety and Monitoring Board (DSMB) -- The DSMB will have the responsibility of monitoring the safety of ongoing clinical trials and reviewing final protocols and consents before initiation.  The DSMB is established by the NICHD and reports to the NICHD Director.  The DSMB is composed of individuals with expertise in clinical trial design and conduct, statistics, urogynecology, urology, fecal incontinence, a consumer representative, and ad hoc members when dictated by protocol topics.

The Data Coordinating Center acts as liaison with the DSMB.

In addition, the NICHD Pelvic Floor Disorders Network has established policies and procedures that govern its operations, including publications.  These policies and procedures can be amended by the Steering Committee and the NICHD and are consistent with current NIH policies and procedures.

Dispute Resolution - Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel 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 dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Lisa Halvorson, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-1646
Email: lisa.halvorson@nih.gov

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-3415
Email: duperes@mail.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 74 and 92.