National Institute of Allergy and Infectious Diseases (NIAID)
Reissue of RFA-AI-18-046
March 26, 2020 - NIH Late Application Policy Due to Public Health Emergency for United States for 2019 Novel Coronavirus (COVID-19). See Notice NOT-OD-20-091.March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077. July 26, 2019- Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128
August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for the Vaccine and Treatment Evaluation Units (VTEUs) to implement clinical site protocols (clinical research, clinical trials) for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, including prognostic and predictive markers, and devices for the treatment and prevention of infectious diseases as part of NIAID Infectious Diseases Clinical Research Consortium (IDCRC). This initiative seeks to fund additional VTEUs with a specific focus on enhancing capability and capacity of current research in controlled human infection models for malaria and influenza, and implementation of treatment and prevention trials in endemic areas for malaria and neglected tropical diseases. While the scientific focus will be on product evaluation for NIAID priorities for this FOA, including malaria/neglected tropical diseases, the VTEUs must also provide capacity to perform clinical research on sexually transmitted infections, respiratory infections, and enteric diseases, in addition to providing surge capacity to address emerging infectious diseases. The VTEUs will coordinate with the Leadership Group (LG) for the IDCRC, awarded in December 2019, a program which provides for overall administrative and scientific leadership for the clinical research and clinical trials conducted.
February 19, 2020
30 days prior to receipt date.
April 14, 2020
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
New Date July 15, 2020 per issuance of NOT-OD-20-091. (Original Expiration Date: April 15, 2020)
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 purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for the Vaccine and Treatment Evaluation Units (VTEUs) to implement clinical site protocols (clinical research, clinical trials) for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, including prognostic and predictive markers, and devices for the treatment and prevention of infectious diseases as part of NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The VTEUs coordinate with the Leadership Group (LG) for the IDCRC, a program which provides for overall administrative and scientific leadership for the clinical research and clinical trials conducted. This initiative seeks to fund additional VTEUs with a specific focus on enhancing capability and capacity of current research in controlled human infection models for malaria and influenza, and implementation of treatment and prevention trials in endemic areas for malaria and neglected tropical diseases. While the scientific focus will be on product evaluation for NIAID priorities for this FOA, including malaria/neglected tropical diseases, the VTEUs must also provide capacity to perform clinical research on sexually transmitted infections, respiratory infections, and enteric diseases in infected patients and healthy volunteers, in addition to providing surge capacity to address emerging infectious diseases.
The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat and identify NIAID priority pathogens, emerging infectious diseases and other infectious disease outbreaks is a critical NIAID need. Timely, prospectively generated clinical trial data is a critically important part of this process, and NIAID's Division of Microbiology and Infectious Diseases (DMID) has supported the Vaccine and Treatment Evaluation Units (VTEUs) since the 1960s. These sites have and continue to play a prominent role in supporting studies of promising vaccine and therapeutic candidates for influenza, malaria, tuberculosis, pneumonia, cholera, whooping cough and many other infectious diseases, in children, adults, and high-risk populations (e.g., pregnant women).
NIAID has a dual mandate to both pursue a robust infectious disease research portfolio and be prepared to quickly launch a research response to newly emerging and reemerging infectious diseases, especially in the international setting. The VTEUs must address the same dual mandate. Historically, they have designed and conducted a broad range of clinical studies and clinical trials in people of all ages and risk categories. When a new infectious disease emerges, the VTEUs must rapidly mobilize to evaluate countermeasures against new threats. For example, in 2009, immediately upon availability of product, NIAID initiated trials of experimental vaccines against novel H1N1 influenza. The trials involved thousands of volunteers recruited by the VTEUs and other medical centers nationwide. Subsequently, similar efforts have been repeated with stockpiled pre-pandemic influenza vaccines as part of influenza pandemic preparedness efforts. More recently, the VTEUs were able to rapidly initiate clinical trials and other studies in response to emerging epidemics, such as Waves 1 and 5 of the H7N9 avian influenza outbreaks in Asia, and in response to the Zika epidemic in 2016.
The VTEU trials and studies have provided data that informed public health policy. For example, data provided by the VTEUs has been instrumental in licensure decisions (e.g., H5 pre-pandemic influenza); informed policy regarding utilization of stockpiled vaccine (e.g., anthrax); informed standard of care (e.g., rotavirus vaccine); and provided data to support product inclusion in the Strategic National Stockpile (e.g., Modified Vaccinia Ankara (MVA) smallpox vaccine).
Research Objectives and Scope
In 2019, 9 awards were made in response to the Request for Applications (RFA-AI-18-046) providing support of the Vaccine and Treatment Evaluation Units (VTEUs). VTEUs provide the scientific, clinical, administrative, and organizational structure to support implementation of clinical trials and studies for the Infectious Diseases Clinical Research Consortium. This initiative seeks to support additional VTEUs with a focus on enhancing capability and capacity of current research in controlled human infection models for malaria and influenza, and implementation of treatment and prevention clinical trials in endemic areas for malaria and neglected tropical diseases. The VTEUs will conduct interventional trials and clinical research studies for vaccines and other preventive biologics, therapeutics, diagnostics and devices targeting infectious diseases primarily in healthy outpatient populations or in patients within ambulatory clinic settings, such as sexually transmitted infection (STI) clinics, which routinely treat infections generally not requiring hospitalization. Clinical research concepts developed into protocols and implemented by the VTEUs may arise from the LG, the research community, NIAID staff, as well as from DMID’s preclinical and early product development programs.
The VTEUs will be capable of implementing clinical trials testing products that address a public health need that would not be done in the private sector. Such products include pre-pandemic influenza vaccines for stockpiling, first-in-human studies of new antibiotics, and biologic countermeasures that may be deployed in a public health emergency. The VTEUs will need to implement clinical trials in disease endemic areas.
VTEU Program Elements
VTEUs are organized to maximize flexibility to address current needs, potential surge capacity to conduct multiple clinical research projects and respond rapidly to evolving research opportunities, and the capacity to address a wide array of infectious diseases. Through the integrated structure, the VTEUs will implement clinical research through recruitment of normal healthy volunteers and patients with common outpatient infections such as sexually transmitted infections or respiratory viral infections, in addition to performing human challenge studies in areas such as malaria, enteric pathogens and respiratory pathogens, and Phase 1 first-in-human pharmacokinetic studies. Note that each individual VTEU will not need all capabilities; however, all capabilities will be necessary for the IDCRC to function as a complete program. All clinical trials conducted by the VTEUs must adhere to NIAID/NIH and other applicable policies and requirements and comply with Good Clinical Practice (GCP) requirements. Additionally, VTEU PD(s)/PI(s) will contribute to the research agenda by serving on area specific expert working groups formed by the LG.
Applications must contain the following Program Elements: Administration, Clinical Sites, Clinical Laboratory, Pharmacy, Data Management, Quality Management, Research Laboratory, in addition to an application Overview. Applications lacking one or more Program Element will be considered incomplete and will not be reviewed.
The VTEU Administrative functions consist of protocol development, implementation and management, VTEU oversight and coordination, fiscal and project management, and administrative support for all activities of the VTEU. The VTEU provides oversight for the following clinical-related activities: adherence to regulatory compliance, coordination of data management actions, clinical staff training, and process development to conduct internal quality control and quality assurance consistent with NIAID clinical research and regulatory policies. The VTEU administration develops and coordinates multiple processes to monitor activities, budgets, timelines, and develops strong bi-directional communications practices among all participant locations, sites and functions. In addition, the leadership of the Administrative section coordinates with NIAID to ensure integration of NIAID-supported resources and services (e.g., safety monitoring, statistical and data management, etc.) into all VTEU program elements, as required.
The VTEU Administration will coordinate the activities related to the identification of research opportunities for junior investigators with the VTEU. These opportunities may take the form of small clinical research projects, classroom training in clinical research and statistical analysis, participation on committees, participation as junior investigators on studies and protocol teams, and exposure to other aspects of clinical research on infectious diseases.
Other functions may arise on a protocol by protocol basis. As part of the overall organization, management and oversight of the VTEU functions, the following assurances and functions are integral to the VTEU program elements:
A VTEU clinical site is the location(s) where clinical research is conducted, such as a hospital, academic medical center, outpatient clinic, health department, or community health center where clinical trial participant recruitment and retention occurs, and local protocol management and other clinical research activities are conducted. International clinical sites are allowed as part of the VTEU collaboration. The VTEUs are considered the fixed sites funded through cooperative agreements with NIAID for continuous operation in implementing clinical research developed through LG activities. At times of specific need, the LG or NIAID may request the VTEU to identify and incorporate protocol-specific sites to meet goals or recruitment needs of the supported research. Protocol specific sites are clinical research sites opened for capacity to implement specific protocols when eligibility criteria cannot be met by fixed sites alone, or when surge capacity is required to respond in a high priority research area. The NIAID priority is focused on enhancing capability and capacity of collaborations with clinical sites in areas endemic for malaria and neglected tropical diseases.
The VTEU Clinical Laboratory is responsible for conducting protocol-specific clinical and safety testing, specimen collection and processing, clinical data collection, storage and shipment of collected specimens from VTEU locations. Clinical laboratory services may be provided by multiple VTEU-affiliated laboratories, by locally available clinical laboratories (e.g., hospital pathology laboratory), or by a single (clinical) laboratory. All proposed clinical laboratories must meet and maintain specific requirements to ensure compliance with Good Clinical Laboratory Practice (GCLP). Clinical laboratories at proposed international clinical sites will need to demonstrate compliance with GCLP and should have procedures in place for international shipment of specimens.
The VTEU Pharmacy is responsible for receipt, storage, inventory, identification and processing, and dispensing study product(s), as well as records management of products in accordance with GCP, applicable United States regulations, NIAID guidelines and local requirements or regulations. Pharmacy services are provided by multiple VTEU-affiliated pharmacies, by locally available clinical pharmacies (e.g., hospital pharmacy dispensary), or by a single pharmacy. All proposed pharmacies must meet and maintain specific requirements to ensure compliance with Good Clinical Laboratory Practice (GCLP) and provide a Pharmacist(s) of Record (PoR) responsible for overseeing all VTEU pharmacy-related activities.
The Data Management section is responsible for oversight of the data and specimens collected from the clinical sites, protocol-specific sites, laboratories and pharmacies. The data management section will collect, record, and send the data to the LG Statistical Support Unit (SSU) (for non-Investigational New Drug [IND]/Investigational Drug Exemption [IDE] data) or the NIAID-supported Statistical and Data Coordinating Center support contract (SDCC) (for IND data). The LG will coordinate with the VTEU to provide the appropriate methods used to ensure data integrity based on IND or non-IND status. The Data Management section will develop processes and procedures that will allow for the secure, rapid transfer of clinical data, specimen data, and reports from the VTEUs, Laboratories and Pharmacies to the LG SSU or the NIAID SDCC, as appropriate. The data management function resides within the VTEU. In addition to QA/QC procedures inherent to the GLP and GCLP processes, the VTEU data management function will incorporate and plan for additional QA/QC processes associated with the overall VTEU, Laboratories, and Pharmacies role(s) in ensuring the integrity of data collection and transfer.
The VTEU will be responsible for development and implementation of processes for conducting internal quality control and quality assurance, consistent with NIAID clinical research policies and SOPs.
The VTEU Research Laboratory is responsible for conducting research on specimens, and clinical data collected. Research laboratory services might consist of, for example, immunogenicity assay development and characterization; identification, qualification, and verification of biomarkers; or pharmacokinetic analyses and assays. All proposed research laboratories will ensure the application of rigorous research methodology, QC verification, and appropriate transfer of outcomes from data or sample analyses to the data management facility. All proposed research laboratories must meet and maintain specific requirements to ensure compliance with Good Laboratory Practice (GLP).
Additional resources provided by NIAID:
Annual Program Meetings
The Program Directors (PDs)/Principal Investigators (PIs) of the VTEU, collaborators, and key personnel will participate in annual program meetings of all VTEU awardees. These meetings may be held in conjunction with the LG annual program meeting. These meetings provide a forum for program and progress updates from each VTEU to the consortium members, and the LG (if applicable), and the sharing of ideas, procedures, and research outcomes.
NIAID will provide Core funds to support the clinical research personnel, locations, facilities and general administrative support directly to the VTEUs and NIAID will provide Protocol funds to implement approved clinical research protocols to the LG on an annual basis.
Renewal to RFA-AI-18-046
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
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NIAID intends to commit an estimated total of up to $1.5M, depending on funds availability, in Core funding in FY 2021 for 1-2 awards.
Budgets for direct costs up to $400,000 per year may be requested for Core funds.
The proposed project period must be 6 years.
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 not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.
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.
Applicants may be PD(s)/PI(s) on only one application to this FOA.
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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.
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:
Maryam Feili-Hariri, PhD
National Institutes on Allergy and Infectious Diseases (NIAID)
Subsection A. Overview of the VTEU Research Program - required - 12 pages
Subsection B. Administration - required - 30 pages
Subsection C. Clinical Sites - required - 30 pages
Subsection D. Clinical Laboratory - required - 12 pages
Subsection E. Pharmacy - required - 12 pages
Subsection F. Data Management - required - 6 pages
Subsection G. Quality Management - required - 6 pages
Subsection H. Research Laboratory - required - 12 pages
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional requirements.
Facilities & Other Resources:
Clinical Sites: Describe the unique facilities and features of the VTEUs. Describe the unique facilities available at the clinical sites to recruit, screen, and enroll in a timely manner as well as follow, retain and provide the clinical care required for the proposed and potential research areas. Describe the facilities available for emergency care of research subjects should the need arise.
Clinical Laboratory: Describe the unique facilities and features of the Clinical Laboratories that will support the collection, identification, coding, and storage of patient data, including biological specimens. Describe the storage facilities appropriate for various specimens or reagents, and how the facilities will be monitored and secured based on the nature of the data.
Pharmacy: Describe the unique facilities and features of the Pharmacies that will support the request, receipt, identification, manipulation and handling and storage of study products or devices. Describe the storage facilities appropriate for various study products and pharmacy supplies and how the facilities will be monitored and secured based on the nature of the study product.
Data Management: Describe the unique facilities and features of the data management section to support the processes for the reliable and accurate collection and recording of the data, and the features of the facilities that will enable rapid and secure transfer of all data types to the SDCC or the LG SSU, depending on the IND status.
Research Laboratory: Describe the unique facilities and features of the Research Laboratories that will support the receipt, storage and handling of data and the performance of various biologic, genomic or pharmacokinetic assays as requested by the LG. Describe the storage facilities appropriate for various specimens or reagents, and how the facilities will be monitored and secured based on the nature of the data.
Describe the applicant organization's experience with the management and execution of single IRB studies and/or reliance agreements. Include the plans, processes and communication strategies to meet the requirements of sIRB.
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional requirements.
Describe the leadership team of the VTEU, including the PD(s)/PI(s), key personnel and collaborators, in terms of previous experience with implementation, oversight, and overall management of a complex project of this scope. Expand on the specific skills of the PD/PI that will contribute to the success of collaborative and synergistic activities.
Describe the PD(s)/PI(s) experience with conducting clinical research in the following populations: healthy adults (age 18-64), healthy adults (age =/>65), healthy children, pregnant women, those with STIs/at risk for STIs, those with infections routinely treated in outpatient settings (e.g. respiratory infections), malaria and neglected tropical disease patients, and any relevant experience with controlled human infection models. Include in your description the type of study (observational, clinical trials, clinical trial under IND), the duration of the study (in years), and the number of subjects enrolled and retained.
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional requirements.
Beginning in Year 1, include funds for travel by the PD(s)/PI(s), collaborators, and key personnel to attend annual meetings in the Bethesda, MD area for 1.5 days to update NIAID on progress and future directions.
In the budget section, applicants should request funds to support the infrastructure and operations of the VTEU (Core Funds - CF) under the heading Core funds. Applicants should not request funds for the implementation of protocols (Protocol Funds - PF) in response to this FOA. Instead PF will be determined and provided to the VTEUs and LG as protocols are approved through a collaborative process among the IDCRC, LG, VTEU and NIAID.
Specific Aims: Describe the specific aims of the VTEU with respect to the uniqueness of the organization to address the priority scientific areas to be supported by the IDCRC, including research using controlled human infection models for malaria and influenza, and implementation of treatment and prevention trials in endemic areas for malaria and neglected tropical diseases.
Research Strategy: The Research Strategy must consist of a single attachment including subsections A-H, as designated below.
Subsection A: Overview
Subsection B: Administration
Subsection C. Clinical Sites
Subsection D: Clinical Laboratory
Subsection E: Pharmacy
Subsection F. Data Management
Subsection G. Quality Management
Subsection H. Research Laboratory
Letters of Support: The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).
Provide a letter signed by the appropriate institutional official(s) from the applicant institution documenting specifics of institutional commitment for the duration of the award. Provide letters of support from clinicians or collaborators whose support is necessary for the successful conduct of the scope of research, including letters from proposed sites where participants will be recruited, if not part of key personnel. Provide letters of support from collaborating laboratories and pharmacies. Applicants must include letters of support from any proposed consultants or contractors.
The following modifications also apply:
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
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 with the following additional requirements.
Although applicants must be prepared for clinical trials, definite plans for such involvement will not be possible at time of application. A Study Record should not be completed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instruction.
Note: Applicants must enter at least one delayed onset study record and check the box "Anticipated Clinical Trial?"
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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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: Will the proposed VTEU provide adequate structure and function to engage in the priority scientific areas proposed by the IDCRC for the duration of the award? Are the plans for future surge capacity sufficient to ensure smooth and orderly transition of priorities, such as funding, staffing resources, and site selections?
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: Are the proposed investigators established in their respective areas of research and/or administration, and will their collective experience as a team ensure appropriate oversight and execution of the research?
Do the PD(s)/PI(s) have research experience in designing, implementing, conducting, analyzing, and completing clinical research to evaluate diagnostics, therapeutics, devices, and vaccines for the diagnosis, treatment, and prevention of infectious diseases, including relevant experience in controlled human infection models?
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?
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
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?
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?
Specific to this FOA:
Are the proposed approaches for the efficient utilization and sharing of resources, and/or other cost-containment measures appropriate and feasible to support the proposed VTEU configuration?
Specific to the Clinical Sites:
Specific to the Clinical Laboratory:
Specific to the Pharmacy:
Specific to the VTEU Data Management:
Specific to the Quality Management:
Specific to the Research Laboratory:
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?
Specific to this FOA: Do the proposed facilities support the nature and type of clinical research to be conducted by the VTEU? Are the plans for physical security and storage within clinical and research (optional) laboratories and the data management recording and transfer functions adequate to ensure confidentiality of data? Are there adequate, available, and appropriate facilities to recruit, screen, enroll, follow, retain and provide the clinical care required for the proposed research areas?
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 thecategories 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.
For Renewals, the committee will consider the progress made in the last funding period.
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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by National Institute of Allergy and Infectious Diseases, 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.
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 National Advisory Allergy and Infectious Diseases Council.
. The following will be considered in making funding decisions:
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.
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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor 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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIAID Project Scientist will coordinate the activities listed below. NIAID staff assistance will be provided by an NIAID Program Officer, Clinical Project Manager(s), and Medical Officer(s). These staff will be identified at the time of award.
Data Access. The awardees retain the rights to the data, consistent with current DHHS, PHS, NIH and NIAID policies; however, NIH will have access to all data generated (raw and analyzed) and may periodically review it. This includes a review of data as recorded on the case report forms or in the central database, and external checking against the original source documentation as required by federal regulation and NIAID as the IND/IDE sponsor. NIAID may request from the VTEU specific data analysis needed for programmatic activities or for issues related to NIAID plans with other partners. The NIH may provide public access to selected data sets generated with the use of public funds within a reasonable time after primary analysis and publication. 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.
Areas of Joint Responsibility include:
Dispute Resolution:Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
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 agreementsare 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.
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Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
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Contact Center Telephone: 800-518-4726
Seema Nayak, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Maryam Feili-Hariri, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
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