Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title

Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-DK-11-026

Companion FOA

None

Number of Applications

Applicant organizations may submit only one application for a Research Site and one application for a Data Coordinating Center from an institution. See Section III. 3. Additional Information on Eligibility.  

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

93.847

FOA Purpose

The present Funding Opportunity Announcement (FOA) supports the development of a cooperative research network (Symptoms of Lower Urinary Tract Dysfunction Research Network, or LURN) to develop and qualify symptom-based instruments to measure early, late, transient, and persistent symptoms both in males and females, and to better define the phenotypes of men and women with symptoms of lower urinary tract dysfunction (LUTD).

Key Dates
Posted Date

December 6, 2011

Open Date (Earliest Submission Date)

February 14, 2012

Letter of Intent Due Date

February 14, 2012

Application Due Date(s)

March 14, 2012, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July, 2012

Advisory Council Review

October, 2012

Earliest Start Date(s)

December, 2012

Expiration Date

March 15, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Lower urinary tract dysfunction is common in both men and women, and the incidence and prevalence increase with advancing age. Symptoms of lower urinary tract dysfunction (LUTD) encompass all urinary symptoms including storage, voiding, incontinence, and post-micturition symptoms. Symptoms of LUTD are highly prevalent and occur in both genders to a similar extent, with 51% of men and 59% of women exhibiting storage symptoms; 26% of men and 20% of women exhibiting voiding symptoms; and 17% of men and 14% of women exhibiting post-micturition symptoms.

The impact and burden of symptoms of LUTD to individuals and to the nation are enormous. Those patients with symptoms of LUTD suffer considerable morbidity resulting in a significant decrease in quality of life for both the patient and his/her partner. According to the results from the NIDDK supported Urologic Disease in America project, the diseases related to the prostate, only one of the organs that may contribute to lower urinary tract symptoms, cost 2.5 billion dollars to the nation in 2000 exclusive of outpatient treatments. A recent analysis of the National Health and Nutrition Examination Survey showed that when urinary incontinence was defined as "urine leakage during physical activity, before reaching the toilet, and during nonphysical activity", the prevalence is 51% in women and 14% in men aged 20 years old or older. When the aging of the population is taken into account, the financial challenge caused by bothersome LUTD is expected to increase dramatically. Treatments for these symptom-based disorders are only modestly effective at best, have significant side-effects, wane in their effect over time, and are costly.

The specific term of "Lower Urinary Tract Symptoms" (LUTS) more commonly relates to infravesical obstructive and bladder irritative symptoms excluding urinary incontinence. The canonical "LUTS" has been traditionally attached to a specific urologic organ, the prostate. In men over the age of 50 LUTS is usually attributed to urinary obstruction caused by an enlarged prostate (e.g., benign prostatic hyperplasia, or BPH). However; recent research suggests that common pathophysiological changes (e.g. inflammation, fibrosis, connective tissue, vascular or neurologic factors) in more than one urologic organ may be responsible for a group of symptoms. Moreover, involvement of non-urological adjacent organs (e.g. colon), remote organs (e.g. brain), other diseases or conditions (e.g. diabetes), medication (e.g. diuretics), or lifestyle factors (e.g. drinking habits) may contribute to the development or modify the severity of lower urinary tract symptom complexes. Thus, the underlying causes for symptoms of LUTD appear more complex than previously appreciated and potentially involve both organ/tissue-specific and more systemic contributions. To address this evolving view, new and novel approaches are needed to better define and categorize different lower urinary tract symptom complexes and identify the underlying cause(s) of observed symptoms and their proportional contribution to overlapping symptom profiles seen in numerous urologic conditions.

Although there are many validated measurement tools used in research evaluating LUTD, they are usually burdensome and do not capture all symptoms related to the lower urinary tract. The American Urological Association symptom score (AUA SS), which was initially intended to objectively quantify the symptoms of BPH patients, is widely used in clinical practice. In addition, it is often used as an endpoint in clinical trials to assess symptom-based clinical improvement in benign lower urinary tract disease. However, objective improvement in symptoms of LUTD following an intervention, does not always correlate with patient expectations, satisfaction and goal achievement, which are critically important for successful management of LUTD. Therefore, overreliance on using the current AUA SS to evaluate all types of symptoms of LUTD limits clinical relevance due to weak correlation with patient satisfaction. This also may be scientifically invalid and impede continued scientific progress in assessing study outcomes relative to symptom bother. Thus, better measurement tools that focuson patient reported outcomes (PRO) are essential to measure early, late, transient, and persistent symptoms of LUTD both in men and women.

Despite years of basic and clinical research, many fundamental questions regarding the etiology and natural history of LUTD remain unanswered. Although epidemiologic studies have uncovered many associations with symptoms of LUTD, there is still a lack of understanding of causality. There is an urgent need for a comprehensive assessment of symptoms of LUTD through phenotyping patients using combined, multidisciplinary approaches, including studies of the natural history of symptoms; structure and function of the lower urinary tract, including contributions of other non-urological factors; interplay between different organs and systems; and biological marker discovery efforts. Special emphasis has to be placed on integrating complimentary epidemiological and basic science approaches to provide a systemic characterization of early symptoms of LUTD, the transient changes, causes and predictors of both progression and response to therapy. Advances and emerging technologies now allow development of better phenotyping methods for individuals with symptomatic conditions. This phenotyping approach should address the long-standing questions in the field and enhance our knowledge allowing for development of improved treatment and prevention strategies.

The goals outlined in this funding initiative were developed in part, based on discussions at the 2011 NIDDK Meeting on Measurement of Urinary Symptoms (MOMUS).

Research Objectives

The long term goal of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is to construct an interdisciplinary  team of researchers to collaboratively 1) develop, test, and ‘fit for purpose’ qualify symptom-based measurement tools to quantitate early, late, transient and persistent symptoms of LUTD in men and women; 2) deep-phenotype a small targeted population from relevant patient cohorts  using a multi-disciplinary, integrated approach in order to expand our understanding of the pathophysiological causes of symptoms of LUTD; and 3) to identify methods and collect data and/or samples to find predictors and/or biomarkers of symptom initiation, flare, and progression that may inform strategies to prevent and/or manage disease; and 4) distribute data, research tools and samples to the research community.

The objective of this initial funding opportunity is to solicit applications for Research Sites comprised of teams of investigators equipped with the appropriate knowledge and skills to employ cutting-edge technologies for the development of an item bank founded largely in patient reported outcome (PRO) measures, with accompanying psychometric evaluation, validatity, and cognitive testing for symptoms related to LUTD. The item pools for symptoms of LUTD should be evaluated in large general populations and in well-defined enriched populations. After proper testing for dimensionality, differential item functioning, item fit, other psychometric properties, and proper calibration, a common metric will then be developed for administering via a tailored short form and/or computer adaptive testing (CAT) system.

The first goal is to develop new and moreinclusive, reliable, and generalizable measures of clinical outcomes including, for example, bother, adaptation and exacerbation.  Focus groups may be needed to develop key concepts important to patients that are not currently captured . Measurement of PRO is extremely important in clinical trials because quantitative measures such as reduction of post-voiding residual urine or a higher urinary flow rate after an intervention directed toward an organ like prostate or bladder may not translate into an important qualitative benefit to the patient.

An important goal is to develop useful outcome indices that will be adopted for a wide range of future epidemiologic studies and clinical trials. Thus, the applicants should consider that the new PRO measurement tools are expected to substitute for the currently used symptom scoring instruments and serve as a standalone and sufficient measure of outcome as well as a part of a composite index. It is also expected that the new tools would be applicable to a broad population of men and women, the research community, and hopefully professional organizations for the purpose of adapting its use in standard clinical practice. The new PRO measures will be tested populations often under-represented in clinical studies. It is anticipated that the new LUTD symptom measures will later be constructed in different languages and be available for use in international clinical trials and cross cultural research. The new symptoms of LUTD PRO measures will be useful across a broad range of clinical research to assess response to interventions. To achieve this goal, the tool development and clinical testing and validity testing will ultimately need to meet or exceed the scientific and psychometric rigor established by the Patient Reported Outcomes Measurement Information System (PROMIS) network in order to ensure widespread acceptance of the new tools by all interested stakeholders, including ultimately the FDA (http://www.fda.gov/cder/guidance/) and its European counterpart, the European Medicines Agency (EMA) (http://www.ema.europa.eu/).

The second and complementary goal of the LURN is to advance our understanding of the underlying pathophysiology of symptoms of LUTD, the natural history, the causative risk factors for initiation, flares, and progression, and importantly how these collectively contribute to defining patient phenotypes and disease definitions. The individual phenotyping will be an essential part of this effort and should use and validate the developed instruments during the first phase. Studies should define anatomical, physiological and psychological characteristics contributing to underlying pathophysiology to provide comprehensive patient phenotypes with symptoms of LUTD. Patient cohorts comprised of distinct phenotypes may be assembled collaboratively to facilitate the identification of factors important for diagnosis, staging, or to determine response to treatment. The studies are expected to address questions of key clinical relevance and provide findings useful for future clinical prevention and/or intervention strategies.

Finally, collection of data and/or biosamples for identification and validation of predictor and prognostic biomarkers will be an integral aspect of this study. Proposed basic cellular, molecular, and biochemical studies could examine the basis of initiation, exacerbation, remission and progression of symptomatic LUTD at the cellular level using human study materials. These studies could emphasize the identification and validation of new biomarkers that may be used to differentiate the causes of LUTD, predict progression, or response to therapy. Novel and innovative imaging and new technology based in diagnostic and prognostic methods could be utilized to diagnose and differentiate the causes of LUTD. Imaging studies can add our understanding the causes and mechanisms of symptoms related to LUTD initiation, exacerbation, remission and progression. Predictive mathematical and/or computer models should identify those individuals who are likely to progress and require further more invasive therapies.

A Funding Opportunity Announcement information delivery conference call is scheduled for December 20, 2011 between 11:00 a.m. and 12:00 p.m. Eastern Standard Time to describe and explain the objectives, expected structure and functioning of the LURN.  Additional conference calls may also be held.

Organizational Structure

The LURN structure will include one Data Coordinating Center (DCC) and up to 3 Research Sites (RS). The DCC will have a Director with a tract record of experience and success in the past working as a director for major clinical studies. The RSs can have one or multiple Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)). The PD(s)/PI(s) should be scientists with a proven track record of research in their respective fields; one being PRO measurement, and the second being clinical phenotyping of patients with LUTD including both male LUTS, and male and female urinary incontinence.

The Data Coordinating Center (DCC) will provide expertise in the coordination of multi-site research studies and for data analysis. To promote quality control, this shared DCC will serve as the central coordinating center for data acquisition and statistical analyses functions for the multi-site efforts. The DCC will also provide overall administrative support for the LURN including the scheduling and logistics of investigator and External Expert Panel (EEP) meetings and teleconferences; development and maintenance of a LURN website and secure computerized systems for data collection and sharing; preparation of reports and analyses for the projects; and other scientific, administrative, and organizational functions, as required. The DCC will work with the NIDDK Biorepository to coordinate procedures for RS sample collection by widely accepted best practice methods, banking, annotation/blinding, coding, shipping, processing, receipt, and storage of study data that is to be maintained in the Biorepository. The DCC will also be responsible for data acquisition, statistical analyses, and other scientific, administrative, and organizational functions for the LURN investigators-lead projects during the study period. In addition, the DCC will coordinate with the NIDDK Biorepository to prepare the collected data for eventual archiving and distribution.

Applicants for the DCC are expected to establish collaborative relationships with a diverse group of investigators from different disciplines. DCC applications should include evidence that they are able to provide support for different types of data collection, management, analysis, and able to coordinate biosamples collection, banking, coding and shipping to the NIDDK Biorepository.

Applicants for RSs must describe in their application the PD(s)/PI(s) responsible for the PRO measurement tool development and the phenotyping studies. It is expected that the PRO measurement tool development researchers and the phenotyping researchers work in close collaboration. Those researchers responsible for developing the measurement instruments for symptoms of LUTD must have access to the patients. The applications for the PRO measurement tool development and phenotyping studies should both include methods and techniques that can be applicable and usable in other centers. Applicants should be open to work in collaboration with other studies. Final common protocols and research study designs for multi-site studies will be established upon initiation of the program. A sequential approach will be utilized in these research efforts. While preparation for phenotyping studies may be allowed during the early phases; it is anticipated that the PRO measurement tool development will precede the phenotyping efforts. PRO measurement tool development and phenotyping studies will have to be in coordination; and applicants are strongly encouraged to develop strategies on sequential study designs where the new measurement tools can be used and tested in the phenotyping studies. On the other hand, clinical input and access to the patients is essential during the PRO measurement tool development phase. The secondary phase of LURN studies should concentrate on combined use of the PRO measurement tools in selected targeted groups of patients, and development of methods for imaging, novel measurements, biomarkers, and computational analysis. The applicants for RSs should clearly indicate that the PD(s)/PI(s) responsible for the pneotyping efforts have the experience and tract record on individual phenotyping and have large enough practice to recruit patients.

Administration and Meetings

A LURN Steering Committee will be composed of RS PD(s)/PI(s), DCC Director and NIDDK Project Scientist. The Steering Committee will meet regularly in-person and by telephone conference calls to develop and implement the study protocols, review progress of the projects, discuss results, interpret findings, and develop manuscripts for peer reviewed publications. A Chairman for the Steering Committee will be selected by the NIDDK. The Steering Committee will establish an Executive Committee that will be comprised of the Chairman of the Steering Committee, DCC Director, and NIDDK staff. The Executive Committee will make operational decisions for the Steering Committee meetings by means of telephone conference calls in order to advance the conduct of the studies.

The NIDDK will assist the Steering Committee in the development of LURN study protocols; will monitor the progress of all projects, will assist investigators in the analysis and interpretation of data and will aid in preparation of manuscripts for publication.

The NIDDK will establish an External Expert Panel (EEP) to monitor the research efforts and advise the NIDDK and LURN investigators on the progress of the studies. RS and DCC applicants must not suggest potential participants for this committee in their applications.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

NIDDK intends to fund an estimate of 4 awards, corresponding to a total of $1,250,000, for fiscal year 2012. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets are not limited, but need to reflect actual needs of the proposed project. The expected award for each RS and DCC will be up to $250,000 in direct costs.

Award Project Period

The maximum proposed project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are  eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

Investigators from diverse fields and those who have not been traditionally involved in studies of symptoms of lower urinary tract dysfunction (LUTD), but who bring expertise from relevant disciplines, are highly encouraged to apply as Research Site (RS) Program Director(s)/Principal Investigator(s) (PD(s)/PI(s) or Data Coordinating Center (DCC) Directors. It is expected that the LURN will catalyze the involvement of junior faculty and new investigators both in urological sciences and in related other fields of study. Investigators may not be listed as participants in more than one application.

Because all relevant expertise may not be present at a single institution to achieve the goals of the LURN, applicants are strongly encouraged to establish a multi-disciplinary team for a RS or DCC through collaborations with research groups outside their own institution.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit only one application for Research Site and one application for Data Coordinating Center from an institution.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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

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

Letter of Intent

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

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

The letter of intent should be sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
E-mail: FC15Y@NIH.GOV

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

PHS 398 Research Plan Component

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the SF424 (R&R) Application Guide with the following modification:

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.

Foreign Institutions

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (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.

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 SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review and responsiveness by NIDDK, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at fc15y@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115

Section V. Application Review Information

1. Criteria

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

Overall Impact

Reviewers will provide an overall impact/priority 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).

Scored Review Criteria

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

Significance

Does the 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?  

Investigator(s)    

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?Do the investigators have the expertise in developing, testing and validating Patient Reported Outcomes (PRO)? Do the researchers involved in tool development have access to patients? Do the investigators have any track record of working together on PRO measures? Do the DCC Director and personnel have prior experience and a record of success in leading a similar DCC facility in support of multiple projects and multiple sites?  Are sufficient expertise and experience present for coordination and execution of LURN statistical analyses in support of multi-site research efforts?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the plans proposed both by the measurement tools development researchers and phenotyping researchers adequate to reach the goals of the FOA? Is there a proposed strategy for sequentially aligning the PRO measurement tools with the phenotyping studies? Is there a suitable plan in place for integration, communication, and collaboration among the different researchers responsible for LUTD PRO tools development and phenotyping within the RS and with their counterparts in other RSs and other RS`s collaborating institutions (if any)? Does the RS have a stated commitment to multi-site integration, communication, and collaboration with other LURN RSs and the DCC? Is there a language for accepting to work on a common protocol PRO measurement tool development and for phenotyping? Does the DCC have a commitment to integration, communication, collaboration and efficient data, tools and samples distribution with other LURN RSs? Is sufficient expertise in place to address potential operational requirements of the LURN, including the coordination of all meetings, agendas, conference calls, tracking of publications, protocol development, website development and maintenance, preparation of reports and analyses for presentation to the LURN investigators, development of computerized system for data transfer, and other operational activities? Is sufficient experience present in coordinating procedures for RS sample collection, banking, annotation/blinding, coding, shipping, processing, receipt, and storage of study data in the Biorepository?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there a plan for the measurement tools developers and researchers in phenotyping to act together in a complementary way on the goals of this FOA? Will the scientific environment allow the PRO measurement tools developers to have access to patients? Is the scientific environment suitable for phenotyping researchers to interact with the PRO tools developers? Does the Data Coordinating Center (DCC) have sufficient and relevant expertise in multi-site study coordination, and in data collection, storage, sample blinding, distribution, quality control, and analysis? Is the research environment suitable for sequentially achieving the goals of this FOA?

Additional Review Criteria

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations

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/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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 NDDK National Advisory Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The Directors will have the primary responsibility for overseeing the project(s) within their RS or DCC. They are also responsible for ensuring that their Site/Center is adequately represented at all LURN in-person meetings as well as on specified conference calls.

LURN investigators are expected to work collaboratively and cooperatively within their Institutions, with all Network sites, DCC, and all sponsoring organizations in this multi-site study. This includes implementation of and adherence to protocols, as well as assuring quality control of the data collected and its subsequent analysis.

The DCC will perform analyses as outlined in the study protocols, and as suggested by the members of the Steering Committee, as well as propose original analyses to the collaborative group for their consideration. The DCC will prepare periodic reports as requested by the Steering Committee, the NIDDK and the NIDDK-appointed External Expert Panel. The DCC will establish, maintain and provide appropriate oversight to any subcontracts for external data collection, consultants, and other necessary adjuncts to the study.

The NIDDK has established a central Biorepository for the archival and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The DCC will work with the NIDDK Biorepository to coordinate procedures for biosamples collection based on widely accepted best practice methods, banking, coding, shipping, processing, receipt, and storage of study data and samples that are to be maintained in the Repository for future distribution to the scientific community. All samples and data transferred to the NIDDK Biorepository will be under the custodianship of the NIDDK, although the LURN Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time.

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:
The NIDDK Project Scientist will be a member of the Steering Committee and the Executive Committee and other selected subcommittees of the LURN. The NIDDK Project Scientist will have substantial scientific involvement in assisting the Steering Committee in the development and refinement of LURN study protocols, monitoring the progress of projects, quality control, interim data analysis, final data analysis and interpretation, preparation of publications, and assisting in coordination and performance monitoring. The NIDDK will appoint an External Expert Panel (EEP).

Additionally, an NIDDK Extramural program official will be responsible for the administrative and financial aspects of the cooperative agreements. The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or LURN policy and procedure, or substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or a human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

A LURN Steering Committee will be the main governing board of the study. It will be composed of RS PDs/PIs and DCC Director, and the NIDDK Project Scientist. The Steering Committee will meet regularly in-person and by telephone conference calls in its role as the primary body responsible for developing and implementing LURN study protocols, reviewing progress of projects, and discussing results and preparing manuscripts for publication and presentation. The Steering Committee will also be responsible for establishing study policies in such areas as access to patient data and specimens, Ancillary Projects (if any), and performance standards. Each member of the Steering Committee will have one vote (NIDDK will have one vote) and all major scientific discussions will be determined by a majority vote of the Steering Committee. Members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. The Steering Committee will establish an Executive Committee which will make operational decisions for the LURN between Steering Committee meetings.

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Ziya Kirkali, M.D.
Senior Scientific Advisor
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Two Democracy Plaza, Room # 627
6707 Democracy Blvd., MSC 5458
Bethesda, MD 20892
Phone: (301) 594-7717
Fax: (301) 480-3510
E-Mail: kirkaliz@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date)

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
E-mail: FC15Y@NIH.GOV.

Financial/Grants Management Contact(s)

Ms. Carolyn Kofa
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Grants Management Branch
2DEM - 2 Democracy Plaza, 746
6707 Democracy Blvd. MS 5450
Bethesda, MD 20892-5452
Telephone: 301-594-7681
Email: kofac@niddk.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


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