CFDA#
93.855, 93.856
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Funder Type
Federal Government
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IT Classification
B - Readily funds technology as part of an award
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Authority
U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH),National Institute of Allergy and Infectious Diseases (NIAID)
Summary
This program invites applications from groups of two (2) or more institutions to participate in a clinical studies program to improve the long-term outcome of transplant recipients (thoracic organ, abdominal organ and vascular composite tissue). The Clinical Trials in Organ Transplantation (CTOT) program will support a cooperative, multi-institutional consortium for the conduct of interventional trials (Phase 1, 2, or 3) or observational clinical studies in organ or vascularized composite allotransplantation (VCA). Each clinical study must include associated mechanistic studies that focus on immune-mediated pathologic processes in allotransplantation or on mechanisms of immune activation and quiescence. The goals of this research will be to target immune-mediated causes of morbidity and mortality in transplant recipients and evaluate interventions to address them.
History of Funding
None is available
Additional Information
The objective of this FOA is to support multi-center interventional clinical trials and/or observational studies in adult candidates for and recipients of organ or vascularized composite allotransplantation. All clinical trials and studies must include associated studies of immunologic mechanisms performed on samples from study subjects and, if appropriate, human controls. These mechanistic studies may include cellular assays (ELISPOT, flow cytometry, etc.), antibody assays, gene expression studies, genomic studies, studies of the microbiome, or any other assays that will contribute to the scientific goals of the proposed studies.
Examples of clinical trials, observational studies and associated mechanistic studies include, but are not limited to, the following:
- evaluation of improved, less toxic or more specific immunosuppressive agents or regimens;
- protocols designed to minimize pharmacologic immune suppression;
- interventions in the donor that will result in improved recipient outcomes;
- identification and validation of biomarkers that will:
(1) enable accurate non- or minimally-invasive monitoring of the recipient’s immunoreactive state, so that therapy can be individualized and proactive, or
(2) act as reliable surrogates for important clinical transplant outcomes;
- studies designed to improve understanding of pathogen-specific immune reconstitution or heterologous immunity in transplant recipients;
- implementing and validating strategies to improve surveillance, diagnosis, prophylaxis and/or treatment of infections in transplant recipients.
This FOA will NOT support research involving:
- hematopoietic stem cell or mesenchymal stem cell transplant, except as a component of a study of organ transplantation or VCA;
- pancreatic islet transplantation for treatment of type I diabetes;
- xenotransplantation;
- autologous reconstructive surgery;
- investigations in animal models, unless mechanistic assays specifically linked to a clinical study require the use of animals, e.g., a mouse footpad assay;
- protocols for which the primary target population is pediatric transplant recipients.
Applications proposing such studies will be considered non-responsive and will not be reviewed.
The CTOT consortium will work collaboratively with the Clinical Trials in Organ Transplantation in Children (CTOT-C) consortium (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-12-005.html), a similar clinical studies program in pediatric organ transplantation. Applicants may include children under the age of 18 in their study if: (1) there is strong scientific justification for doing so, (2) the majority of the subjects in the proposed study will be adults, and (3) they have personnel with the appropriate pediatric expertise. If such a study is funded, the investigators will be required to establish a collaboration with investigators in the CTOT-C consortium (www.ctotc.org).
Milestones
General milestones addressing completion of subcontracts to clinical and laboratory sites, accrual of subjects, and time to last patient/last visit must be provided in the application as part of the research strategy.
Explicit, detailed, and quantitative yearly milestones will be used for assessing progress and success by NIAID program staff when recommending continued funding on an annual basis. Some of these milestones will be developed post award, when the final research protocols have been developed, and some will require steering committee input. In order to maximize utilization of CTOT program resources, the NIAID may re-budget individual U01 funds based on recommendations of the Steering Committee and/or based on NIAID assessment of availability of funds or progress toward yearly Milestones.
Data Coordination and Management and Clinical Trial Support
Data coordination and management and clinical trial support will be carried out by a separately-funded data and clinical coordinating center, the Statistical and Clinical Coordinating Center (SACCC) (see http://www.CTOTstudies.org). Each participating institution will be responsible for providing primary study data to the SACCC for management, quality control and analysis using procedures and standards determined by the CTOT Steering Committee (see below) and the SACCC. The quality and integrity of CTOT studies require that all analyses are performed on data from the central database, and that these analyses are performed or have oversight by the SACCC. The SACCC will provide technical assistance and data management services to CTOT participating institutions with respect to quality control, uniformity of data collection, management of the collective database and data analysis; centralized data collection and management; and quality assurance.
Each applicant team shall include one or more individuals qualified to provide biostatistical support for the proposed project. SACCC statisticians will work collaboratively with study team statisticians to develop statistical analysis plans for protocols. The SACCC will also provide clinical site monitoring, regulatory support, and drug and specimen distribution. More information about SACCC responsibilities can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-09-015.html.
CTOT Steering Committee
A Steering Committee will serve as the governing board to direct the collaborative work of the CTOT consortium. All major scientific decisions will be made by the majority of the voting members of the Steering Committee. Voting members of the Steering Committee will include one CTOT Program Directors/Principal Investigators (PD(s)/PI(s)) from each awarded CTOT grant, one additional investigator from each awarded CTOT grant, a senior statistician from the SACCC, and the Chair of the Mechanistic Studies Sub-Committee (see below). The NIH Project Scientist will be a non-voting member of the Steering Committee. CTOT Steering Committee responsibilities are described further under Section VI, below.
The CTOT Steering Committee will also recommend procedures to solicit applications for CTOT Ancillary Studies Fund support (described below), make recommendations to support specific applications through the Ancillary Studies Fund, recommend budget allocations for each project to be supported through the Fund, and monitor the progress of funded projects.
Mechanistic Studies Subcommittee
The CTOT Steering Committee shall appoint a Mechanistic Studies Subcommittee to review proposed mechanistic studies and make recommendations to the Steering Committee. One representative from each awarded grant will serve as a voting member of the Mechanistic Studies Subcommittee; additional non-voting members may be nominated and approved by the Steering Committee. The NIH Project Scientist will serve as a non-voting member. Responsibilities of the Mechanistic Studies Subcommittee are described further under Section VI, below.
Publications Subcommittee
The Steering Committee will establish a Publications Subcommittee to develop publication policies and procedures for the CTOT consortium. See Section VI, below.
Ancillary Studies Fund
An Ancillary Studies Fund of up to $600,000 total costs per year for the entire program may be available, depending on the availability of funds. This amount includes the cost for the management of the Ancillary Studies Fund. These funds are to be used to support additional mechanistic studies (i.e., studies which are in addition to those proposed as an integral part of a clinical trial) performed on existing, archived biological specimens from CTOT studies or on prospectively collected specimens from a CTOT study. All projects supported by the Ancillary Studies Fund must be within the scientific scope of the parent grant. The CTOT Steering Committee will make recommendations to the awardee of the Ancillary Studies Fund as to the goals, priorities, and evaluation criteria for the use of the Fund. Any use of Ancillary Studies funds must comply with all applicable HHS/NIH policies. Use of these funds is limited to CTOT investigators or non-CTOT investigators who establish a collaboration with a CTOT investigator. After award, one awardee institution will be selected by the NIAID to manage the Ancillary Studies Fund for the entire CTOT program.