Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
RFA-DK-18-030 U01 Research Project Cooperative Agreements
Pain is a common problem in Medicare End-Stage Renal Disease (ESRD) Hemodialysis (HD) patients, but its prevalence varies widely by geography, dialysis unit, and possibly, ethnicity. Perception of pain has been linked to decreased quality of life, lack of social support, depressed mood and other mental health disorders. Chronic opioid prescription has been identified in approximately 20% of US ESRD HD patients, far higher than the rate in Medicare comparison populations. Opioid doses prescribed to HD patients exceed Centers for Disease Control and Prevention (CDC) recommendations. Prescription and dose level have been associated with increased hospitalizations and mortality in this population.
Interventions including behavioral modification techniques such as Cognitive Behavioral/Group Therapy and social media platforms for sharing information and enhancing social support have not been employed to reduce the rate of opioid prescription and opioid use, as well as addressing comorbid related issues such as depression, anxiety and pain in the HD population. Medical interventions such as use of naloxone and buprenorphine have not been evaluated by randomized controlled trials in HD patients who use opioids. The ESRD HD population, because of its continuous longitudinal participation in monitored treatment and the availability of data resources is an ideal population in which to launch and monitor interventions.
The Hemodialysis Opioid Prescription Effort (HOPE) Consortium, composed of a Scientific and Data Research Center (SDRC) and 5 to 7 Clinical Centers (CCs) will develop an intervention to simultaneously address the problem of pain and opioid use in US HD populations a) by initiating multipronged pain treatment tailored individually to each patient, without opioids, and b) by using buprenorphine and other novel agents to reduce dependence on opioids in affected patients. Multipronged interventions can include behavioral modification techniques such as Cognitive Behavioral/Group Therapy, which can be designed according to each participants psychosocial profile, as well as alternative therapies, such as acupuncture and can use social media platforms for implementation and evaluation. Analyses will consider comorbid illnesses (such as diabetes mellitus and mental health disorders) and social determinants of health (such as socioeconomic status, social isolation, social support, residential factors and perception of racial discrimination) to identify novel risk factors for pain and opioid use in this population. End points will be chronic opioid prescription rate, prescription drug dose, pain control, patient satisfaction with care, perception of quality of life, hospitalization rates and mortality. Real time risk factor and outcome data may be captured using the electronic health record (EHR), by leveraging and expanding an existing pilot set of more than 200 standardized data elements identified and prioritized for comprehensive chronic kidney disease (CKD) care by the NIDDK CKD eCare Plan Working Group.
December 10, 2018
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.
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.
The Hemodialysis Opioid Prescription Effort (HOPE) Consortium, composed of a Scientific and Data Research Center (SDRC) and five to seven Clinical Centers (CCs) will develop an intervention to be tested in a randomized controlled trial to simultaneously address the problem of pain and opioid use in adult US in-center hemodialysis (HD) patients receiving chronic opioid prescriptions a) by initiating multipronged pain treatment tailored individually to each patient, without opioids, and b) by using buprenorphine and/or other novel agents to reduce dependence on opioids and improve outcomes in affected patients. Multipronged interventions may include behavioral modification techniques such as Cognitive Behavioral/Group Therapy, which can be designed according to each participants psychosocial profile or alternative therapies, such as acupuncture, and can use social media platforms for implementation and evaluation. Interventions may also address treatment of depression and/or anxiety in appropriate patients as a strategy to ameliorate perception of pain. It is hypothesized that an intervention in hemodialysis patients receiving chronic opioid prescriptions focused on treating pain, taking into account individual patient characteristics, such as their psychosocial and mental health status, coexisting medical conditions, perception of pain, and coping mechanisms and strengths will reduce opioid medication prescription rates and/or morphine milligram equivalent (MME) doses compared with usual care. Whether a medical intervention, such as therapy with buprenorphine, can reduce the dose of opioid medication prescribed as well as the number of patients receiving chronic opioid prescriptions is unknown in this population. Such questions can be addressed in two- or three-arm trials. Analyses will consider comorbid illnesses (such as diabetes mellitus and mental health disorders), substance use (such as alcohol or benzodiazepines), and social determinants of health (such as socioeconomic status, social isolation, social support, and perception of racial discrimination) to identify novel risk factors for pain and opioid use in this population.
The primary endpoint is likely to be either a clinically meaningful reduction in the rate of opioid prescription or in participant MME dose. Other endpoints will be pain control, patient satisfaction with care, perception of quality of life, hospitalization rates and mortality.
Real time risk factor and outcome data may be captured via the electronic health record (EHR), by leveraging and expanding an existing pilot set of more than 200 standardized data elements identified and prioritized for comprehensive chronic kidney disease (CKD) care by the NIDDK CKD eCare Plan Working Group. The eCare Plan data element set includes new and existing data standards from widely used ontologies (e.g., ICD-10, SNOMED-CT, LOINC, RxNorm, etc) and is intended to enable interoperability of clinical data for research and care.
Research Objectives
This Funding Opportunity Announcement (FOA) will establish a SDRC to work collaboratively with the CCs assembled to design and conduct the trial. The SDRC will accept and manage data electronically submitted from the CCs, which will recruit study participants, conduct interventions, follow participants and collect data.
Each CC will be required to enroll and follow 120 patients in the study. Each SDRC and CC application will submit a plan for screening HD patients to identify those receiving chronic opioid prescriptions and a proposed intervention designed to reduce the dose of opioid medication prescribed as well as the number of patients receiving chronic opioid prescriptions. Patients identified, who consent to participate in the study, will be evaluated to assess their psychosocial status, coexisting medical conditions, perception of pain, and coping mechanisms and strengths.
Applications including any home hemodialysis or peritoneal dialysis patients or children are not responsive to this FOA.
The HOPE Consortium is expected to comprise a wide range of expertise, including but not limited to nephrologists, experts in pain assessment and management and opioid medicine (including practitioners with certification in buprenorphine prescription), biostatisticians, ethicists, data scientists/informaticists and patient advisor participants.
Studies proposed by the successful applicants will be the starting point for discussions regarding the research to be undertaken by the HOPE Consortium awardees. Investigators will devise studies that will be reviewed by a Data and Safety Monitoring Board (DSMB) and approved by the NIDDK. The final study protocol will be designed by the CC and SDRC Program Directors/Principal Investigators (PDs/PIs) and approved by the Steering Committee (SC), and then the DSMB and the NIDDK. Consortial study results are expected to provide evidence for management approaches to pain and minimizing opioid prescription in HD patients.
Applications for the SDRC should consider:
a. How the SDRC will coordinate data collection, perform analyses and prepare study reports for the CCs performing studies, in addition to preparing final protocols for review and approval. The SDRC will be responsible for the conduct of Steering Committee meetings and conference calls. It is envisioned that a successful SDRC will require a nephrologist, an expert in opioid medication prescription with certification in buprenorphine prescription, an expert in pain medicine, a senior Biostatistician, a Master’s level Biostatistician/Epidemiologist and a Database Manager as well as other key staff. All data collected by CCs in single and multi-center studies will be sent to the SDRC for quality control and analysis.
b. The SDRC should include a proposal for an interventional study (with characteristics as described below) to illustrate how the SDRC will operate.
Applications for SDRC should consider and submit :
Applicants for the SDRC are expected to demonstrate the relevance of the preliminary data for the implementation of a definitive randomized controlled trial of a potentially important intervention. How such a proposed intervention might impact the opioid prescription rate, participant perception of pain and quality of life, and morbidity and mortality of HD patients should be justified in detail. Applicants should provide strategies to recruit a diverse and appropriate population for the study, maintain follow-up and limit drop outs. Applicants should consider the unique role of Research Coordinators in the study. Applicants should demonstrate experience with regulatory agency procedures involved in bringing new therapies into clinical practice, in the HD community, as appropriate.
SDRC applications are expected to address common study issues such as:
a. Ability to work collaboratively to establish Consortium Agreements that address: (1) procedures for data sharing among consortium members and data sharing with industry partners and qualified external investigators to provide opportunities to participate via ancillary studies and disseminated data analyses; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biological specimens; (5) procedures for sharing data with the research and clinical communities according to NIDDK policies; and (6) procedures for the HOPE Consortium for reviewing publications, determining authorship, and industry access to publications.
b. Each industry collaboration will be governed by an appropriate Research Collaboration Agreement (e.g. Clinical Trial Agreement [CTA], Research Collaboration Agreement [RCA], etc) with terms that ensure collaboration is conducted in accordance with the terms of the Cooperative Agreement and all applicable NIH policies and procedures. Each industry/SDRC agreement will address ownership of intellectual property discovered from multi-party data generated by the consortium, and the Consortium will develop intellectual property policies and procedures with terms that ensure collaboration and dissemination of research findings are conducted in accordance with the terms of the Cooperative Agreement and all applicable NIH policies and procedures. Consortium policies will require continued submission of data centrally to the SDRC and consortium policies/procedures will address protection of personal medical information records of study participants.
The HOPE Consortium Structure
The HOPE Consortium will consist of one SDRC and five to seven CCs. The SDRC and CC investigators will work collaboratively on the design, planning, execution and analysis of the intervention.
The CCs will be responsible, as a group, for recruiting patients, obtaining biological samples and clinical information from all participants at baseline and during follow-up, and transmission of those data and samples to the SDRC.
The SDRC will be primarily responsible for insuring the scientific integrity, comprehensiveness and robustness of the research design, biostatistics, data quality and storage, implementation, and data analysis of all study protocols. The SDRC investigators, including biostatisticians, will work with the CC investigators to develop the scientific design of the study.
The SDRC will have primary responsibility for ensuring that study data are obtained, stored and available for study both within and eventually outside the Consortium.
The investigators will have the primary responsibility for ensuring that the design of the study, including the primary outcome, is scientifically sound, comprehensive, with sufficient statistical power to study the primary outcomes. The SDRC will provide biostatistical and analytic expertise, and conduct analyses and interpretation of the data in conjunction with the investigators at the CCs. The SDRC will develop and coordinate procedures for and training of research staff throughout the Consortium. The SDRC and CCs will work closely together to achieve the goals of the Consortium.
Administration and Meetings
The Steering Committee (SC) will serve as the governing body of the HOPE Consortium. Its actions and decisions will be determined by majority vote. The SC will be composed of the SDRC and CC Program Directors/Principal Investigators (PDs/PIs), other key investigators and the NIDDK Project Scientist, as well as patient participant representatives, appointed by the NIDDK. The SC will meet regularly in-person in the Bethesda MD / Washington DC metropolitan area, and by telephone or webinar, as necessary, as a full committee and in working groups to develop and implement study protocols. SC responsibilities include: providing input on and approval of all studies developed by the Consortium members prior to study implementation; review and approval of all data analyses, public presentations and publications of research conducted within the consortium; developing procedures for and coordinating training of all research personnel; and development of policies and procedures for submission and approval of research applications using Consortium resources. The NIDDK will select a chair of the SC [Steering Committee Chair (SCC)] either from the PDs/PIs of the CC s, or outside the study group. An Executive Committee (EC) will be comprised of the Steering Committee Chair, the SDRC PDs/PIs, and the NIDDK Project Scientist. Additional CC investigators, NIDDK Program Officers and other NIH officers, patient participant representatives and support personnel may participate in the EC as needed. The Executive Committee will make operational decisions for the Consortium between SC meetings by means of weekly telephone conference calls.
The NIDDK Project Scientist will assist the SC in the development of consortial study protocols, will monitor the progress of projects and functioning of all consortial activities, will assist investigators in the analysis and interpretation of consortial data and will participate in all aspects of the research and in preparation and writing of all manuscripts from consortial studies for publication.
SDRC and CC investigators will devise studies that will be reviewed by a Data and Safety Monitoring Board (DSMB) and approved by the NIDDK. The final study protocol will be designed by the CC and SDRC Program Directors/Principal Investigators and approved by the Steering Committee, and then the DSMB and the NIDDK.
A DSMB will be appointed by the NIDDK at the beginning of the funding period, to provide input on the design of studies prior to their implementation. The DSMB will monitor the research efforts and the progress of the studies, and advise primarily the NIDDK as well as the Consortium investigators. The DSMB will include biostatisticians, pharmacologists, nephrologists, experts in pain management and opioid prescription, ethicists, and ESRD patients treated with maintenance hemodialysis. The DSMB will review study protocols prior to implementation, and will monitor progress and safety of the studies.
SDRC applicants should not suggest potential participants for the DSMB in their applications.
The SDRC and each CC will identify two representatives of the population to be studied to serve on a Community Advisory Council, which will provide feedback to the Consortium regarding the design and conduct of the study.
Awardees will meet to finalize the HOPE Consortium study protocol(s). Both CC and SDRC awardees should be prepared to participate in conference calls immediately after funding and should reserve September 23 and 24, 2019 in Bethesda, Maryland for the first Steering Committee meeting.
Applicants should indicate their availability on these dates in their applications.
Awardees must agree to abide by the Network Duality of Interests Policy and Procedures and may need to develop procedures to require study investigators and others associated with the study to identify financial and other conflicts of interest on a routine basis, at least annually, and to share this information with the NIDDK Program staff.
This study is part of the of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative .
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Need help determining whether you are doing a clinical trial?
NIDDK intends to commit up to $5,500,000 in FY 2019 to fund one award.
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
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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.
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.
Multiple PD/PI applications are required for this Funding Opportunity Announcement.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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 should be sent to:
John Connaughton, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email:[email protected]
The Multiple PD/PI plan should include a nephrologist, a specialist in opioid medicine certified in burprenorphine prescription, a biostatistician clinical trialist, and a specialist in pain therapeutics.
All instructions in the SF424 (R&R) Application Guide must be followed.
1-2 day in-person SC meetings will be conducted every 3-4 months for the first year and yearly or more often as needed thereafter in the Bethesda MD / Washington DC area. Applicants should budget accordingly.
Applicants for the SDRC should budget for the support of 2 meetings of a DSMB in the Bethesda MD / Washington DC area in the first year, including travel, lodging and honoraria for up to 15 DSMB members, and at least one such meeting a year in subsequent years.
Research Strategy: The Research Strategy section for the SDRC should include:
SDRC applicants should describe how they will carry out major scientific responsibilities, including:
The following modifications also apply:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
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 and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.
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.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this FOA: Is the study proposed in the application an important and feasible intervention which is likely to favorably affect the opioid prescription rate, and dose, as well as perception of pain and quality of life, and morbidity and mortality of HD patients?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this FOA: Do the investigators have the requisite multidisciplinary experience in nephrology and hemodialysis, working within large dialysis organizations to effect interventions, as well as experience in clinical trials science and psychosocial aspects of medical care (including expertise in mental health disorders), pain management and opioid medicine including certification in buprenorphine prescription, and pain management?
Does the applicant have experience with EHR methodologies to enhance screening, recruitment and follow-up and data capture?
Does the SDRC have expertise in ensuring scientific integrity and robustness of the proposed clinical research studies?
Are the roles and responsibilities of the key investigators and the leadership plan appropriate to achieve the aims of the research?
Does the SDRC have expertise in design and analysis of interventional studies?
Does the SDRC have expertise in design and analysis of opioid prescription and pain management studies?
Does the SDRC have expertise in biostatistics, implementation, adherence, and ensuring data quality?
Do SDRC key investigators have a track-record of research productivity and cooperation within a broad, multi-site research effort?
Does the SDRC provide evidence of sufficient expertise to address potential operational requirements of the HOPE Consortium, including the coordination of all meetings, agendas, conference calls, tracking of publications, protocol development, data collection and storage, website development and maintenance, preparation of reports and analyses for presentation to the investigators and the DSMB, development of systems for data sharing, performance of site visits and other operational activities?
Does the SDRC demonstrate expertise in establishing training and certification for Consortium staff?
Is sufficient expertise in place for the coordination of biosample collection, storage, quality control and distribution (e.g. serum, plasma, DNA, tissue, stool and urine, as applicable) and interactions with the NIDDK Central Repository?
Have the investigators demonstrated that they can work collaboratively to achieve comprehensive identification and follow-up of outcomes related to HD patients in the US?
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 design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Specific to this FOA : Does the SDRC propose innovative approaches to the scientific question(s), research design, biostatistics, data quality, implementation, and data analysis efforts?
Does the SDRC propose innovative approaches to the multipronged pain intervention, ensuring generalizability throughout the consortium?
Does the SDRC propose innovative approaches to a Cognitive Behavioral Therapy intervention for pain, tailored to individual patients psychosocial characteristics, that can deployed in a standardized fashion throughout the consortium?
Does the SDRC propose innovative approaches to the medical intervention to reduce opioid prescription rates and doses?
Does the SDRC propose innovative approaches to achieving comprehensive identification and follow-up of outcomes?
Does the SDRC propose innovative approaches to Research Coordinators facilitation of recruitment of participants, ensuring adherence to interventions and maintaining followup?
Has the SDRC included representatives of the HD patient community and of patients with pain and users of opioid medications to provide advice on the planning and conduct of the studies?
Has the SDRC proposed innovative ways of interacting and partnering with patients to achieve the goals of the FOA?
Has the SDRC proposed innovative methods to ensure meaningful participation of patients advisors throughout the course of the study?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this FOA: Has the applicant for a SDRC proposed an important, well-designed trial focused on amelioration of pain, and limiting opioid prescription rates and doses, in the context of potentially mediating or moderating psychosocial factors?
Is the proposed study likely to be feasible and generalizable?
Are appropriate biomarkers and alternative/surrogate outcomes proposed in the design of the study?
Has the applicant proposed efficient approaches to screening for eligibility for the trial, employing human resources as well as the EHR?
Has the applicant identified appropriate drug doses, pharmacokinetic and pharmacodynamic aspects of therapy in hemodialysis patients and considered adverse events?
Has the applicant outlined evaluation of potential outcomes for a pharmacologic intervention study?
Are the proposed end-points, stopping rules and safety considerations scientifically and clinically valid?
Are the safety considerations and follow-up plans designed to ensure patient well-being during and after the studies?
Has the applicant provided letters from large dialysis dialysis organizations acknowledging the ability of SDRC investigators to recruit HD patients from the particular dialysis facilities?
Has the applicant provided back up plans for recruitment?
Has the applicant presented a multipronged pain intervention that can be uniformly protocolized and applied across the Clinical Centers?
Has the applicant demonstrated expertise in and understanding of issues involved in meeting planning, coordination and administration of multicenter studies across sites, monitoring progress, handling and presenting data, and provided a detailed plan on how they will accomplish these tasks?
Does the SDRC propose research study designs and analytical approaches to achieve the goals of this FOA?
Does the SRDC propose integrated analyses of the clinical and treatment data in participants?
Has the SDRC provided adequate evidence for planning and conducting biostatistical analyses for the needs of the Consortium?
Does the research plan provide relevant materials to the NIDDK Central Repository for sharing outside the Consortium?
Have the SDRC investigators considered pitfalls in attempts to recruit the participant population comprehensively, including issues related to obtaining informed consent and ensuring longitudinal follow up, and protection of personal and medical information, enhancing adherence and limiting dropout rates, in addition to using data provided by the EHR?
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 individuals of all ages (including children and older adults), 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?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Study Timeline
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) 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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not applicable.
Not applicable.
Not applicable.
Not applicable.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Information regarding the disposition of applications is available 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.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
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 or agreed upon by both parties, to the NIDDK Program Official including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Official may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.
7. 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.
8. Agree that any third-party (including both industry and academia) collaboration should be governed by a research collaboration agreement (e.g. Clinical Trial Agreement, Research Collaborative Agreement, Memorandum of Understanding, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures. The NIDDK Program Official may consult with others at NIH, including the NIDDK Technology Advancement Office.
9. Any involvement of a third party (including both industry and academia) in the study, including access to any study data; study results; using the name of the study; or the name of the NIH or NIDDK, is permitted only after written concurrence by the NIDDK Program Official who may consult with others at NIH including the NIDDK Technology Advancement Office.
10. Study investigators are required 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. Prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Central Repository to develop a Data Sharing Plan and 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, storage and sharing 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. Subsequently samples and data will 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://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.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 Project Coordinator, 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 Project Coordinator 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 NIDDK Project Scientist or Project Coordinator 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 Project Coordinator 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:
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.
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.
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.
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.
Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.
Areas of Joint Responsibility include:
In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:
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, in consultation with the Steering Committee. 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.
Dispute Resolution
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.
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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Paul L Kimmel MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-1409
Email: [email protected]
Norma Deguzman
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-1810
Email:[email protected]">[email protected]