National Institute of Allergy and Infectious Diseases (NIAID)
May 29, 2020 - NIAID Late Application Policy for NIAID-Specific RFAs with Due Dates in June 2020. See Notice NOT-AI-20-053.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
Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for the NIAID Childhood Asthma in Urban Settings Clinical Research Network Leadership Center (CAUSE-LC). The CAUSE-LC will provide the overall scientific strategy and organizational structure to the CAUSE Clinical Research Network and will interact closely with the CAUSE Clinical Research Centers (CAUSE -CRCs) to support the conduct of multi-site clinical studies and trials with the ultimate goal of developing effective interventions or asthma prevention approaches applicable to children residing in low-income urban settings.
January 29, 2020
30 days prior to the application due date
June 19, 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.
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.
NIAID has a long-standing interest in understanding and reducing the disproportionate burden of asthma among children living in low-income urban communities and has funded research initiatives towards this goal over the previous 3 decades. Previous NIAID-sponsored asthma-related initiatives include: a) the National Cooperative Inner City Asthma Study (NCICAS, 1991-1995) which identified cockroach as a major allergen for urban residents with asthma and demonstrated the effectiveness of an Asthma Counselor intervention; b) the Inner City Asthma Study (ICAS, 1996-2001), which demonstrated the effectiveness of an environmental intervention aimed at reducing allergen exposure among inner-city children; c) the Inner City Asthma Consortium I (ICAC I, 2002-2008), which conducted clinical trials evaluating the biomarker exhaled nitric oxide as a guide for asthma therapy, the use of omalizumab therapy for inner-city children with asthma and established URECA, a birth cohort; d) the Inner City Asthma Consortium II (ICAC II, 2008-2014), which conducted a large asthma phenotyping study, a clinical trial evaluating the use of omalizumab for fall exacerbations, and conducted safety and biomarker trials of cockroach immunotherapy. The current Inner-City Asthma Consortium III (ICAC III, 2014-2021) consists of 10 clinical sites and 6 mechanistic sites. The ongoing ICAC III has completed a clinical study determining the transcriptomic signature of asthma exacerbations and is conducting a clinical trial evaluating the effectiveness of mepolizumab among exacerbation prone children with asthma and a trial of cockroach subcutaneous immunotherapy for asthma.
URECA, which was initiated in February 2005, is a longitudinal birth cohort study designed to elucidate risk factors involved in the immunopathogenesis and the clinical manifestations of recurrent wheeze\asthma among children living in low-income urban communities. The cohort completed recruitment in early 2007 with 609 infants enrolled and its current size is approximately 454 children. Since birth, the cohort has been followed by: (i) telephone interviews every 3 months; (ii) annual home visits; (iii) nasal lavages for viral detection and, more recently, transcriptomics; and (iv) annual clinic visits. In addition to blood sampling, depending on the age of the study participant, clinical tests such as spirometry, allergen skin testing, and bioelectric impedance analysis are performed during the annual clinical visit. By the time of award, all study participants will be between 14 and 16 years old. The current URECA protocol is available at (https://www.niaid.nih.gov/sites/default/files/URECA-IV-Addendum.pdf).
Objectives and Scope
The CAUSE Clinical Research Network will conduct observational studies and clinical trials to further improve our understanding of asthma and to develop effective interventions and asthma prevention approaches tailored to children of low-income families living in urban communities.
Research supported by this FOA will involve a) children of families living in census tracts within US Office of Management and Budget-defined Metropolitan Statistical Areas (MSAs) where =10% of families have income below the poverty level and b) children of families who have publicly-funded health insurance, but live in MSA census tracts where <10% of families have income below the poverty level.
Areas of research of interest include, but are not limited to:
Other areas of interest include studies that fall under the general objective of elucidating the causes of asthma in children living in low-income, urban communities or improving immunomodulatory strategies for the prevention or treatment of asthma in those communities.
In conducting its research projects, the CAUSE Clinical Research Network is encouraged to incorporate unbiased, hypothesis-generating methodologies and systems biology analytic approaches.
The CAUSE Clinical Trial Network will also have the task to follow the participants of URECA to age 17 and to conduct studies utilizing URECA clinical and environmental data and URECA biosamples.
Areas of interest involving the URECA cohort include but are not limited to:
Overall Structure of the CAUSE Clinical Research Network
The CAUSE Clinical Research Network will consist of distinct entities that will operate as a single network: the CAUSE Leadership Center (CAUSE-LC) and the CAUSE Clinical Research Centers (CAUSE-CRCs).
The objectives of the CAUSE-LC are to provide scientific strategy and organizational support to the CAUSE Clinical Research Network for the conduct of state-of-the-art clinical research in asthma focusing on children living in low-income, urban communities. The CAUSE-LC will have the overall responsibility for the funding and organization of the network-wide clinical research projects. Under the leadership of the CAUSE-LC, the CAUSE-CRCs will conduct the network-wide CAUSE clinical research projects. Clinical trial/study participants will only be seen at the CAUSE-CRCs. The proposed CAUSE network-wide clinical research projects should include mechanistic research using biologic samples or other materials derived from these projects. To accomplish its mechanistic research objectives, the CAUSE-LC may include collaborations between more than one institution.
It is anticipated that at least three, multi-site, network-wide CAUSE clinical projects will be implemented during the course of the awards. At least one project will be a clinical trial, while the other projects may be either clinical trials or observational clinical studies. In all cases, innovative mechanistic research will need to be included. The clinical projects to be implemented will be chosen by the CAUSE-LC PD(s)/PI(s) from the projects proposed by the CAUSE-LC or by the CAUSE Steering Committee based on scientific advances made during the grant period.
Applications proposing any of the following topics will be deemed non-responsive and will not be reviewed.
Note: Foreign Components may only provide services in support of clinical study or clinical trial activities (e.g. conduct of laboratory assays). Foreign Components must not conduct clinical trials or clinical studies.
Resources provided by NIAID to the CAUSE Clinical Research Network
The following resources will be provided by NIAID to the CAUSE-LCs:
NIAID-DAIT Data, Clinical Safety, and Statistical Center(s) NIAID-DAIT data management center(s) ): The NIAID-DAIT data management center(s) will provide a broad range of clinical research support services, including support for the design and organization of every CAUSE network-wide protocol, development of protocol-related materials, data collection, management and quality control, clinical site monitoring, safety monitoring and reporting, data analysis and manuscript development.
Clinical Trial Sponsorship: NIAID will be the Sponsor for all network-wide clinical trials. NIAID may also choose to be the Sponsor for CAUSE-CRC center-specific, single-site clinical trials conducted under Investigational New Drug (IND) Applications.
NIAID-appointed Asthma and Allergy Data and Safety Monitoring Board (DSMB): All CAUSE network-wide clinical trials and CAUSE-CRC center-specific clinical trials (and some clinical studies if deemed necessary) will be reviewed by DSMB provided by NIAID. After study initiation, the DSMB will conduct periodic safety reviews.
Public Access: NIAID will provide for public access, either through ImmPort or through another NIAID-approved resource. All network-wide clinical trial, clinical study, biomarker and mechanistic data produced by the CAUSE and all CAUSE-CRC center-specific research projects that will be supported by the NIAID-DAIT data management center(s), will be made publicly available by NIAID through the NIAID-DAIT data management center(s). The timetable for public availability of CAUSE data will be determined by the CAUSE Steering Committee and NIAID.
Study Drug Distribution Center: The study drug distribution center will store, label, and distribute study drug used for some or all network-wide CAUSE trials.
CAUSE Clinical Research Network Steering Committee
The CAUSE Clinical Research Network Steering Committee will be the forum for CAUSE to discuss network-wide studies and to advise the CAUSE-LC PD(s)/PI(s) on scientific and organizational aspects of the network's activities. The Steering Committee will also receive information and discuss the progress of individual CAUSE-CRC center-specific research projects, but it will not be involved in the development or implementation of these projects.
Structure of the CAUSE Clinical Research Network Leadership Center
Leadership Center Administration. This will have the responsibility for the administrative oversight, staffing and fiscal management of the CAUSE-LC. In addition, the LC Administration will be responsible for establishing CAUSE-LC governance and maintaining the CAUSE-Steering Committee or other committees that the network will establish.
Clinical Operations. This will have the overall responsibility of organizing, administering and funding the network-wide clinical projects, which includes development, implementation and management. Clinical Operations will disburse protocol-specific funds to the CAUSE-CRCs participating in the network-wide clinical projects and will establish and maintain a biorepository for biologic samples collected during the course of the CAUSE network-wide clinical projects.
Clinical Research Projects: Each application to the CAUSE-LC RFA must propose 4 independent network-wide CAUSE clinical research projects. Each of these projects must address a different research question, however there may be some overlap. In addition, the CAUSE-LC must provide follow-up for the URECA birth cohort participants up to age 17 and propose research to be conducted with data from this cohort. It is anticipated that the network-wide CAUSE projects proposed will utilize all the CAUSE-CRC sites in more than one project.
Specifically, CAUSE-LC applications must propose:
CAUSE Protocol Funds
Protocol funds will be disbursed by the CAUSE-LC to the CAUSE-CRC sites participating in network-wide clinical research projects to support the conduct of those projects.
For more information see the NIAID Research Funding site Questions and Answers for RFA-AI-19-074 found at the following:Section VIII. Other Information for award authorities and regulations.
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.
NIAID intends to commit up to $7.0 million in FY 2021 to fund 1 award.
The proposed project period must be 7 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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.
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:
Jennifer H. Meyers, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
The Research Strategy must consist of the following sub-sections with the indicated page limits:
Subsection A: CAUSE-LC Overview-one required-12 pages
Subsection B: CAUSE-LC Leadership Center Administration- one required-12 pages
Subsection C: CAUSE-LC Clinical Operations-one required-12 pages
Subsection D: CAUSE-LC Clinical Research Projects- four required-12 pages each
Subsection E: Continuation and Completion of URECA birth cohort -one required-12 pages
Provide a PDF file with the name “Staffing Plan”. This should contain a staffing plan for the proposed CAUSE network-wide clinical projects. The staffing plan should include the staff that will be required at the LC for the proposed projects to be appropriately executed and should indicate the qualifications and expertise that will be required for each position. Positions may include: coordinators for network-wide activities such as day-to-day administration, single IRB activities, project specific training for staff or laboratory support of mechanistic research studies. Separately indicate the staff that will be required at the CRCs for the execution of the same network-wide projects. Do not name individuals or sites.
All instructions in the SF424 (R&R) Application Guide must be followed.
Include funds with justification for the following:
Specific Aims: List the overarching long-range goals and objectives of the CAUSE-LC including the administration and operations as well as of the proposed network-wide clinical projects.
Research Strategy: The Research Strategy consists of the following subsections:
Subsection A: CAUSE-LC Overview
Provide an overview of the proposed scientific strategy and vision of the CAUSE.
Subsection B: CAUSE-LC Administration
Subsection C: CAUSE-LC Clinical Operations
Describe the personnel and the procedures and processes that the CAUSE-LC will use for the implementation and management of the proposed clinical projects.
Subsection D: CAUSE-LC Clinical Research Projects
Subsection E: Continuation and Completion of the URECA Birth Cohort
Propose a URECA continuation/completion protocol that includes the following information:
If investigational drug(s) or device(s) are to be provided by the manufacturer at no cost, provide letter(s) of commitment.Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
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.
Section 2 - Study Population Characteristics
2.5 Recruitment and Retention Plan
Describe actions to be taken to address problems with recruitment or retention of study participants.
Section 3 - Protection and Monitoring Plans
3.1 Protection of Human Subjects
3.1.1. Risks to Human Subjects
3.1.1.b Study Procedures, Materials and Potential Risks
For all research projects provide the following information on:
Section 4 - Protocol Synopsis (only available for a study record that proposes a clinical trial)
4.2 Study Design
4.2.a Narrative Study Description
For multi-visit studies, provide a description of the study design including the procedures and activities that can occur at each visit (schedule of events).
Section 5.1 - Other Clinical Trial-related Attachments
Describe the plan to obtain required investigational agent(s).Delayed Onset Study
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.
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.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
While each application will be evaluated in its entirety based on one overall impact score per application, the CAUSE Clinical Research Projects and the URECA clinical protocol within each application will also each receive a separate impact score.
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 for this FOA
CAUSE-LC Clinical Research Projects
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 for this FOA
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 for this FOA
CAUSE-LC Clinical Operations
CAUSE-LC Clinical Research Projects
Continuation and Completion of the URECA Birth Cohort
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?
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.
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 convened by the 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.As part of the scientific peer review, all applications:
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.
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 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:
Determining and coordinating the scientific activities of the network-wide clinical research projects; setting project goals and timelines; accepting and implementing common guidelines proposed by the Steering Committee.
The PD(s)/PI(s) working within the CAUSE-LC structure and with other CAUSE-LC staff will carry out the following functions:
Protocol Development, Review and Approval
Data Sharing Responsibilities
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NIAID Project Scientists will provide guidance and support in the design of research activities, will serve as a resource for protocol design and development, will provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance. In CAUSE-LC network-wide clinical research projects that include clinical trials and, in some cases, clinical studies, an NIAID-assigned Project Scientist will also have Medical Monitor responsibilities.
In addition, an NIAID Program Official will be responsible for the programmatic stewardship of the award and will be named in the award notice.
Two NIAID Project Scientists will be non-voting members of the Steering Committee and participate in all Steering Committee activities, including conference calls, subcommittees and special committees. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientists will participate in this process.
Protocol Review and Approval
All clinical research protocols will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the NIAID DAIT Clinical Research Committee and by the NIAID DAIT Data and Safety Monitoring Board (DSMB) or another monitoring body.
NIAID will serve as the IND/IDE sponsor for all CAUSE network-wide clinical trials requiring an IND/IDE. As part of NIAID’s IND/IDE sponsor responsibilities, the NIAID Medical Monitor will obtain, through the NIAID-DAIT data management center(s), regular reports on adverse events and protocol deviations and will review all serious adverse events. NIAID will be responsible for reporting safety information in accordance with FDA requirements. Also, NIAID, in cooperation with the NIAID-DAIT data management center(s), will prepare and submit the final study reports to the FDA. This role may be delegated by NIAID to another entity (e.g., a collaborating pharmaceutical company).
Clinical Trial Monitoring
NIAID will monitor compliance with good clinical practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the CAUSE-CRCs. At NIAID’s discretion, the NIAID Medical Monitor may request that the DSMB convenes ad hoc to review a serious adverse event or a cluster of adverse events or serious adverse events. The NIAID Medical Monitor may request that the NIAID-DAIT data management center(s) conduct for-cause monitoring visits to a CAUSE-CRC. Depending on the nature of the problem, such visits may be conducted by the NIAID Medical Monitor and/or NIAID staff and the PD/PI of the CAUSE-LC may be asked to participate in those visits.
NIAID reserves the right to terminate or curtail a clinical study or clinical trial for any of the following reasons:
Access to Data
The NIAID Project Scientist or designee will have access to all data generated under this cooperative agreement and may review the data as recorded on the case report forms or in a database. Data must be available for external checking against the original source documentation. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
Coordination with Outside Entities
In the occasion a company provides investigational materials for a CAUSE study, NIAID will be responsible for entering into Clinical Trial Agreements with that company.
External Scientific Advisory Group (ESAG)
NIAID will establish an ESAG composed of clinical and basic science investigators. Members of the ESAG will review and offer input on CAUSE network-wide clinical projects, both during protocol development and during the analysis of results. ESAG members may be invited to attend some CAUSE Steering Committee meetings. The ESAG will submit its recommendations to the NIAID Project Scientists, who will then inform the CAUSE-LC PD(s)/PI(s).
Areas of Joint Responsibility include:
Implementing, monitoring, and updating the clinical research agenda for CAUSE to ensure consistency and relevance with the NIAID scientific priorities.
The CAUSE-LC PD(s)/PI(s) will fully develop the clinical research protocols for the projects supported by this FOA with the participation of the CAUSE Steering Committee, NIAID-DAIT data management center(s) and the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) staff. CAUSE-LC protocols will utilize the protocol templates provided by NIAID.
Reviewing the CAUSE-LC's research activities and goals on an agreed upon schedule (but no less than once every year). Promoting, evaluating and executing opportunities to collaborate with other federal or non-federal research sponsors.
CAUSE Steering Committee
The purpose of this committee is to advise the CAUSE-LC PD(s)/PI(s) on the network-wide clinical projects to be conducted, approve the final clinical trial and study protocols and modify or add protocols as scientifically indicated. The overall CAUSE scientific plan will be reviewed and updated yearly. In addition, the Steering Committee will develop and implement policies and procedures for publicizing the accomplishments and the data resulting from CAUSE studies to the scientific and lay communities and other relevant audiences. The CAUSE Steering Committee will include the PD(s)/PI(s) of the CAUSE-LC (one of those PD(s)/PI(s) will also serve as the Chairperson), a PD/PI from each of the CAUSE-CRCs, the designated Project Leader of the NIAID-DAIT data management center(s), and 2 NIAID Project Scientists. All members of the Steering Committee are voting members with the exception of the NIAID Project Scientists. If one individual is the same PD/PI for both a CAUSE-CRC and the CAUSE-LC, s/he will have only one vote.
Network-wide Clinical Study Implementation and Management
The PD(s)/PI(s) of the CAUSE-LC will work in coordination with the NIAID-DAIT data management center(s), through NIAID, to execute the following tasks related to network-wide CAUSE clinical research projects:
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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Gang Dong, M.D., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Jennifer H. Meyers, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
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