National Institutes of Health (NIH)
Prevention of Lower Urinary Tract Symptoms in Women: Bladder Health Scientific and Data Coordinating Center (PLUS -SDCC) (U01)
U01 Research Project – Cooperative Agreements
93.847, 93.866, 93.313
This Funding Opportunity Announcement (FOA)
invites cooperative agreement research applications to establish a multi-center, multi-disciplinary consortium to be known as the Prevention of Lower Urinary tract Symptoms (PLUS) Research Consortium. This FOA expands NIH's research emphasis from treatment of women with established lower urinary tract symptoms (LUTS) to prevention of LUTS. At present there is insufficient information to undertake large-scale primary and secondary LUTS prevention efforts. The primary objective of this FOA is to plan, perform and analyze the research studies necessary to establish the scientific basis for future prevention intervention studies for lower urinary tract symptoms and conditions in women. The consortium will develop the evidence base for normal or healthy bladder function and to identify behavioral and other risk factors for conditions associated with LUTS. The Consortium will focus on a broad age range from adolescent girls to older non-institutionalized women to set the stage for future research in prevention of lower urinary tract symptoms and conditions with a particular focus on symptoms that are associated with the diagnosis of bladder infections, urinary incontinence, voiding dysfunction, overactive bladder and interstitial cystitis/bladder pain syndrome.
August 18, 2014
October 20, 2014
October 20, 2014
November 20, 2014, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
November 21, 2014
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
Lower urinary tract symptoms (LUTS) are associated with a broad range of diagnoses including bladder infections, urinary incontinence, voiding dysfunction, overactive bladder and interstitial cystitis/bladder pain syndrome. These symptoms are common, costly and consequential for females from childhood to old age. Obesity, diabetes, metabolic syndrome, cardiovascular disease, sexual activity and vaginal childbirth have been associated with increased risk of LUTS. The prevalence of LUTS in the United States is expected to increase substantially over the next several decades as the population ages and the prevalence of risk factors (e.g., obesity, diabetes) increases, imposing an ever increasing medical and economic burden on the population. For the purposes of this FOA, the term bladder will refer to the entire lower urinary tract (bladder, urethra, pelvic floor).
The goal of this FOA is to establish the knowledge and information base necessary to permit future studies of prevention of LUTS in adolescent girls and women. In general, prevention research is a multi-stage process and includes: identification and assessment of risk and protective factors; screening and identification of individuals and groups at risk; development and evaluation of interventions to reduce risk; translation and dissemination of effective preventive interventions into practice; and the development of research methods to support this work. Prevention research targets biologic factors, individual knowledge, beliefs and behaviors, the social and physical environment and health services. Ultimately, this research will inform public and health care professional (HCP) education efforts and evaluate health-related policies and regulations.
At this time there are multiple barriers to the treatment let alone prevention of LUTS. Most women are embarrassed to discuss their bladder symptoms with HCP and are unaware that their condition is treatable. Instead they accept their symptoms as consequences of childbearing and/or aging; something that must be “put up with”. Most HCPs have limited training in evaluation and treatment of LUTS and common bladder conditions, aside from bladder infections. Therefore HCPs are not likely to screen for symptoms or conditions they are not comfortable treating. This reluctance of women and HCPs to engage in a dialogue about LUTS has contributed to a dearth of knowledge about the factors that contribute to healthy bladder function and the factors that initiate, promote and maintain lower urinary tract symptoms.
In the past much of the research has focused on women who seek treatment rather than the much larger group of women who have bothersome LUTS yet do not seek help. By the time most women seek treatment their condition has become chronic and more severe, thus, more difficult to manage and costly. There is an important need to understand how the burden of LUTS in women can be reduced by improving bladder health thereby reducing LUTS through primary and secondary prevention as these approaches are likely to have the greatest impact on reducing the public health burden of LUTS.
This broadening of the focus of women’s urologic research should include early identification of symptoms, understanding factors that contribute to normal or healthy bladder function as well as those biologic, psychosocial, cognitive-behavioral, cultural and environmental factors that lead to bladder symptoms and conditions, and identify women and girls at increased risk for LUTS. Improved patient and HCP education is expected to be a key component of future prevention efforts and would be based on a chronic care model where it is understood that the potential causes and contributing factors for symptoms may change over time making primary prevention or cure of all LUT symptoms and conditions unlikely.
Bladder habits and dysfunctions at one stage of life may affect bladder health in subsequent stages. However, bladder problems are neither a normal part of aging nor inevitable at any stage of life. Many of the factors that negatively impact bladder health at all ages may be modifiable, and healthy bladder habits may prevent bladder symptoms and conditions later in life. Although the prevalence of lower urinary tract symptoms may be substantial in older age, many opportunities for prevention may still be available. There are opportunities to further define and promote healthy bladder habits through focused research, which may lead to improvements in overall health and quality of life.
This FOA will establish a consortium 1) To broadly identify and evaluate the relative importance of the risk and protective factors for LUTS, and then 2) To plan for future primary and secondary prevention intervention research as the evidence is established. The Prevention of Lower Urinary tract Symptoms (PLUS) Consortium will bring together researchers from diverse backgrounds (e.g., women's pelvic medicine, health behavior and preventive science) to plan, perform and analyze studies to: assess knowledge about bladder function in the population, identify personal behaviors that may influence healthy and abnormal bladder function; assess the association of current voiding behaviors and current lower urinary tract symptoms; systematically review the literature (including meta-analyses) to synthesize the evidence for potential risk and protective factors for the range of conditions associated with LUTS described in this FOA; describe the relative importance of both modifiable (including diabetes, obesity, sexual activity and vaginal childbirth) and non-modifiable (age, sex, race/ethnicity) risk factors from completed epidemiological studies, and clinical trials; and test the effects of modifying risk or implementing healthy behaviors on bladder function in small studies of normal females and those with early LUTS.
PLUS Consortium investigators will collaboratively devise a set of studies that will be reviewed by the External Expert Panel and approved by the NIDDK. Thus, all studies proposed in the applications will be a starting point for PLUS Consortium discussions regarding the research to be undertaken. It is unlikely that any proposed research will be undertaken exactly as planned, or at an individual site. Consortium studies will provide new and significant insights into identification of opportunities for future primary or secondary intervention studies and have the potential to provide insights to lead to future mechanistic studies to further understand the development of LUT symptoms and conditions in adolescent girls and women.
It is also anticipated that the Consortium will establish a process through the Scientific and Data Coordinating Center to solicit, evaluate, fund, and implement ancillary pilot and feasibility studies proposed by either non- consortium or consortium investigators on research topics related to the goals of the PLUS Consortium.
The goals and objectives of the PLUS Research Consortium will be complementary to two other NIDDK supported multi-center collaborative networks studying the lower urinary tract, the Lower Urinary Tract dysfunction Research Network (LURN) and the Multidisciplinary Approach to the study of Chronic Pelvic Pain (MAPP) Research Network. When appropriate the PLUS Research Consortium will interact and work collaboratively with these networks.
Note that applications that include LUTS prevention intervention studies will be considered nonresponsive to the RFA and will not be reviewed.
The PLUS Research Consortium will consist of a single Scientific and Data Coordinating Center (SDCC) and up to five Clinical Centers (CC). The SDCC and CC key investigators will work collaboratively for the planning, execution and analysis of PLUS Research Consortium studies.
Guidance for Scientific and Data Coordinating Center
The Scientific and Data Coordination Center (SDCC) will carry out major scientific and administrative responsibilities for the PLUS Research Consortium. The SDCC will provide biostatistical and study design expertise for all Consortium studies, monitor the progress of the studies including data quality, and perform interim and final data analysis for each of the activities and studies undertaken. The SDCC will also manage a pilot and feasibility research program for non-consortium and consortium investigators seeking involvement of investigators with expertise outside of the specialties usually responsive to grants in the area of lower urinary tract conditions. The PD/PIs of the SDCC will work collaboratively with the PLUS Research Consortium Clinical Center PD/PIs in planning and conducting the various research efforts undertaken by the Consortium and provide the organizational and administrative leadership necessary to enable the Consortium to function smoothly.
The major emphasis during the first several years of the PLUS Research Consortium by the SDCC and the CCs will be to identify potential risk and protective factors that can be explored in clinical populations later in the funding cycle.
Administration and Meetings
The PLUS Research Consortium Steering and Planning Committee will be composed of the SDCC and CC investigators and the NIDDK Project Scientist. The Steering and Planning Committee (SPC) will meet regularly in-person and by telephone conferences as a full committee and in working groups to develop and implement study protocols. The SPC will review progress of individual projects, assess and evaluate results, interpret findings, and develop manuscripts for peer reviewed publications. NIDDK will select a chair of the Steering and Planning Committee Chair (SPCC) either from the Program Directors/Principal Investigators or outside the study group. An Executive Committee will be comprised of the SPCC, the SDCC Program Director, selected members (on a rotating basis) of the SPC, and the NIDDK Project Scientist. Additional PLUS Research Consortium investigators, NIDDK Program Officers and support personnel will be a part of the Executive Committee as needed. The Executive Committee will make operational decisions for the PLUS Research Consortium between SPC meetings by means of telephone conference calls. The NIDDK Project Scientist will assist the SPC in the development of PLUS Research Consortium study protocols; will monitor the progress of projects and functioning of all consortium activities; will assist investigators in the analysis and interpretation of PLUS Research Consortium data; and will aid in preparation of manuscripts for publication.
The NIDDK will appoint an External Experts Panel (EEP) to provide input to the NIDDK on the overall research strategy of the PLUS Research Consortium, the design of studies prior to their implementation and the progress made by the investigators once the studies are underway.
The first in-person PLUS Research Consortium Steering Committee Meeting will be a 2 full day (Day 1 from 8 AM - 9 PM and Day 2 from 8 AM - 3 PM) meeting held on 2 consecutive days between September 19 and September 27, 2015, in the vicinity of Washington, DC. Specific dates will be determined once the PLUS Consortium sites are awarded. Subsequent 1-2 day in-person SC meetings will be conducted every 2 months for the first year with at least quarterly in-person Steering Committee meetings thereafter.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The NIH plans to commit $4.5 million dollars in FY15 to support two related funding opportunities, RFA-DK-14-004 and RFA-DK-14-018.
NIDDK intends to commit $ 4,000,000,
NIA intends to commit $ 100,000,
OBSSR intends to commit $ 100,000
And ORWH intends to commit $ 300,000
We anticipate awarding 1 Scientific and Data Coordinating Center and 4-5 Clinical Centers.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Applications budgets are limited to $750,000 direct costs for the Scientific and Data Coordinating Center.
The maximum 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.
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
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.
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.
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.
Investigators with expertise in all scientific disciplines relevant to prevention science irrespective of understanding/ background in lower urinary tract symptoms and conditions are strongly encouraged to apply.
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:
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
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:
The letter of intent, preferably electronically, 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
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. Because all relevant expertise may not be present at a single institution the SDCC investigators may establish a multi-disciplinary team through collaborations with researchers outside their own institution. Investigators with expertise in all scientific disciplines relevant to prevention science irrespective of understanding/ background in lower urinary tract symptoms and conditions are strongly encouraged to apply.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. The Scientific and Data Coordinating Center (SDCC) must have documented expertise in the fields of 1) epidemiology, 2) health behavior, 3) prevention science, 4) biostatistics and 5) clinical care of women/girls with LUTS (primary or specialty care). Note that some of the required expertise may be represented by the same individual. Biosketches must describe expertise and previous experience in designing and conducting epidemiological and other studies in adolescent girls and women.
In addition, personnel should indicate their ability to:
All instructions in the SF424 (R&R) Application Guide must be followed. The SDCC key investigators must each have a minimum of 2 calendar months per year for the entire project period to dedicate to establishing and maintaining PLUS Research Consortium scientific and operational excellence. SDCC must have a total biostatistical effort of at least 4 calendar months per year for entire project period.
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:
An application for the Scientific and Data Coordinating Center must:
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.
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.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout 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.
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 by the Center for Scientific Review and responsiveness by components of participating organizations, 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 firstname.lastname@example.org when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
A Funding Opportunity Announcement informational conference call will be held September 18, 2014, between 11:00 a.m. and 12:00 p.m. Eastern Daylight Savings Time to describe and explain the objectives, expected structure and functioning of the PLUS Research Consortium and to answer any questions potential applicants may have. Additional conference calls may be announced during the September 18, 2014, phone call. Background information from the May 2014 NIDDK Path to Prevention of LUTS in Women Meeting can be found by clicking the Minutes tab at http://www.niddk.nih.gov/news/events-calendar/Pages/LUTS.aspx
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 studies designed to address questions of important clinical relevance? Will the proposed studies provide new and significant insights into the contribution of biological, psychosocial, cognitive-behavioral, cultural and environmental factors to bladder health and risk factors for LUTS?
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? Is appropriate research (prevention scientists, health behavior scientists, epidemiologists and biostatisticians) and primary care and LUTS expertise represented at the SDCC and their collaborating institutions (if any)? Does the SDCC provide evidence of sufficient expertise to address potential operational requirements of the PLUS Consortium, 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 PLUS Research Consortium investigators and the External Experts Panel, development of systems for data sharing, and other operational activities? Do SDCC key investigators have a track-record of productivity and cooperation within a broad, multi-site research effort Do the SDCC key investigators provide evidence that they can provide the 2 calendar months effort over the entire project period and a minimum total biostatistical effort of 4 calendar months?
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? Does the application address the PLUS Consortium research goals through novel, multi-disciplinary approaches across the lifespan? Have innovative biologic, psychosocial, cognitive-behavioral, cultural and environmental factors been considered?
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? Has a well-conceived conceptual framework for the study of the prevention of LUT symptoms and conditions across the lifespan of women and girls been presented? Is the central focus of the proposed studies related to understanding the broad spectrum of factors that contribute to normal or healthy bladder function as well as those that lead to lower urinary tract symptoms and conditions across the lifespan? Will the proposed research identify modifiable risk factors that can be broadly addressed through future prevention interventions? Do applicants present robust rationale or supporting preliminary data relevant to the study(s) proposed? Will the research plan provide insights into the most important populations to target for future primary or secondary prevention interventions? Are all proposed studies collaborative, multi-site (i.e., Trans-PLUS) in design or potential? Has the SDCC provided adequate evidence of relevant expertise in multi-site study coordination, data collection and storage as well as their ability to plan and conduct biostatistical analyses for the spectrum of research studies necessary to establish the evidence base for bladder health and risk factors for LUTS? Is sufficient expertise in place to address potential requirements of the PLUS Consortium, including the coordination of biosample collection, storage, quality control and distribution (e.g. serum, DNA, and urine)? Does the SDCC proposed process for administration of the PLUS Consortium Ancillary Studies program appear adequate? Does the research plan describe 1) The roles, responsibilities of the key investigators with a leadership plan 2) Collaboration across the consortium on the planning, implementation and analysis of all types of research efforts, 3) Integration, communication, resource and data sharing across the consortium and ultimately provide relevant materials to the NIDDK Data and Biorepositories, and 4) Collaboration between investigators within the SDCC and between the SDCC and its collaborating institutions (if any) as well as across the entire consortium?
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?
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?
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.
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 Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Children
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.
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.
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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDDK 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:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
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.
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 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, 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:
1. Developing the research design and study protocol, including definition of objectives and approaches, sample size and power calculations, and establishing procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.
2. Establishing a Steering Committee to implement, coordinate and manage the project(s). Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees will be required to accept and implement the common protocol(s) and procedures approved by the Steering Committee.
3. Designating Protocol Chairs. The Program Directors/Principal Investigators (for studies involving multiple protocols) shall designate a single Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.
4. Implementing collection of data specified by the study protocol. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.
5. Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.
6. Submitting interim progress reports, when requested, to the NIDDK Program Director including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Director may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.
7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.
8. Reporting of the study findings. 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 DHHS, PHS, and NIH policies. The awardee must also be adherent to Study Publication and Presentation Policy. The NIDDK will have access to and may periodically review all data generated under an award. NIDDK staff may co-author publications of findings with awardees consistent with NIH and study policies.
9. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIDDK support; or special access to study results, primary data/summary information, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIDDK.
10. Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and steering committee policies on publications.
11. Maintaining confidentiality of information: The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of a company collaborating with the study.
12. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The PI or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution. In addition, if applicable, the PI or his/her designee will work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Consistent with the goals of the program, subsequently samples and data are expected to be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and, http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for data sharing in multi-center and large single-center clinical studies http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.
13. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html.
In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors http://www.icmje.org/publishing_10register.html).
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NIDDK Project Scientist with substantial involvement will:
1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.
3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.
4. Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:
a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.
b. The NDDK Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.
c. Reviewing procedures for assessing data quality and study performance monitoring.
d. The NIDDK Project Scientist or designee may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.
The NIDDK Program Official identified in the Notice of Award will:
1. Interact with the program director(s)/principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the program director/principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
2. Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.
3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
5. Appoint a Data and Safety Monitoring Board (DSMB) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.
Areas of Joint Responsibility include:
In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:
1. Steering Committee.
A Steering Committee organized by the study investigator(s) will be the main governing body of the study.
The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.
The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.
A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK and by interacting closely with the awardees during protocol development and implementation.
2. External Study Oversight.
An independent Data and Safety Monitoring Board will be established by the NIDDK for Phase III clinical trials or other high risk studies as appropriate. An Observational Study Monitoring Board (OSMB) will be established for observational/epidemiologic studies. These Boards will review study progress, safety data and interim results, as appropriate, and provide guidance to the NIDDK.
Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR Part 16.
When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.
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