Key Dates

Related Announcements

PAR-22-122, Limited Competition: Clinical and Translational Science Awards (CTSA) Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional)

NOT-TR-22-020, Notice of Special Interest: Recruitment Innovation Center (RIC) Topic Area for Limited Competition: Clinical and Translational Science Award Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional)

Issued by

National Center for Advancing Translational Sciences (NCATS)

Purpose

The purpose of this Notice is to inform applicants of one of the topic areas for the June 21, 2022 due date of the NCATS CTSA Program funding opportunity announcement (FOA) PAR-22-122, Limited Competition: Clinical and Translational Science Awards (CTSA) Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional). 

Background

In July 2016, NCATS established the Trial Innovation Network (TIN) with three Trial Innovation Centers (TICs) and one Recruitment Innovation Center (RIC). The TICs were established to transform the CTSA network’s ability to implement multi-site studies by adding innovative network capacity to existing strengths at CTSA Program hubs.  The TICs were designed to be disease agnostic and to provide resources that could be used to reduce delays in trial start-up, speed recruitment, and harmonize processes across the CTSA Consortium for multi-site clinical studies. The TICs provide infrastructure and operational support to multi-site clinical studies and trials through a collaborative process with the funding sponsor (e.g. a categorical NIH institute). The TICs, in collaboration with liaison teams at each CTSA Program hub, provide access to millions of possible participants for research studies and to a wide variety of resources and investigator expertise within the CTSA network.

The TIN has established processes for interactions between CTSA investigators and TIN liaison teams, consultations on clinical trial proposals, single IRB coordination and review, and site identification and assessment. In addition, the TIN maintains an electronic toolbox of clinical trial resources and disseminates best practices/methods for conducting clinical trials through Collaboration Webinars. In its first five years of existence, the TIN has consulted on over 300 proposals from 85 institutions that span 72 different therapeutic areas.

The goal of this Notice of Special Interest (NOSI) is to solicit applications for the June 21, 2022 receipt date of the NCATS CTSA Program funding opportunity announcement (FOA) PAR-22-122, Limited Competition: Clinical and Translational Science Awards (CTSA) Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional). NCATS seeks to fund Clinical and Translational Science Award (CTSA) Trial Innovation Centers (TICs) that will work together to harmonize processes for implementation of multi-site clinical studies across the CTSA network and serve as a national model for innovation in clinical trial management and operations. The TICs will demonstrate and disseminate innovative solutions that can be successfully applied to accelerate trial start-up and recruitment. The TICs will work in partnership with each other, the RIC(s), the individual CTSA hubs and NCATS to improve the implementation of multi-site studies across the CTSA network.

Research Objectives

The primary objectives of the TICs are to demonstrate and disseminate innovative ways to increase the quality and efficiency of multi-site clinical research and to provide unique resources for the CTSA Program’s broad range of multi-site clinical studies. The TICs will provide an innovative infrastructure that at a minimum will consist of a consultation process for multi-site clinical studies conducted by CTSA investigators, resources to help CTSA investigators with the single IRB process and implementation of clinical trial agreements, and events that facilitate dissemination of tools and best practices for clinical trial operations throughout the CTSA network. The infrastructure provided by the TICs should be capable of providing resources to a broad range of clinical studies (e.g. diagnostic testing, interventional trials, trials conducted under FDA regulation (IND/IDE), comparative effectiveness, behavioral research) and accessible to clinical trials funded by federal and non-federal sources of support. The TIN consultation process should be able to support investigators at all career stages and levels of clinical trial experience and should be a resource that will enhance the overall quality and efficiency of clinical trials conducted within the CTSA program.

TICs are expected to serve as clinical and/or data coordinating centers for multi-site clinical studies and to have the capacity to participate in clinical trials that are part of a rapid response to urgent public health needs. TICs may incorporate the testing of new methods, processes, and/or tools into their service as a clinical and/or data coordinating center and thus, demonstrate on a large scale the utility of clinical trial operational innovations developed at one or more CTSA Program hubs. TICs are expected to continuously identify, refine, adapt and disseminate clinical trial operational innovations so that the overall quality and efficiency of multi-site clinical research within the CTSA network steadily increases.

Specifically, an individual TIC should have the staffing and expertise to:

• Create and maintain clinical trial protocols, Manual of Procedures, statistical analysis plans, clinical monitoring plans, case report forms and other clinical trial documents.
• Create and maintain data management plans that facilitate harmonization of clinical data and support a wide variety of forms of data collection – direct entry by clinical center staff, call center, web-based, patient reported outcomes, etc.
• Provide biostatistical support throughout the life cycle of a clinical trial – planning and trial design, protocol development, data collection and analysis, and manuscript preparation/sharing of results.
• Coordinate external services, including procuring study drugs, equipment, and other supplies, and execute contracts with a wide variety of vendors/suppliers.
• Perform site management and clinical monitoring for a wide variety of clinical studies.
• Function as a single IRB for a wide variety of multi-site clinical studies and trials.
• Provide support for FDA-regulated clinical trials.
• Assemble and manage Data and Safety Monitoring Boards for a wide variety of multi-site clinical studies and trials.
• Serve as a Clinical and/or Data Coordinating Center for a wide variety of multi-site clinical studies and trials.

Trial Innovation Network Coordination

NCATS will be responsible for organizing and providing overall support and coordination of consortium-wide activities, by means of cooperative agreements, for the TIN and the CTSA network. In addition to regular grant stewardship by a program officer, a NCATS Project Scientist will be involved with the TICs/RICs as a NCATS partner, consistent with the Cooperative Agreement mechanism.

A Network Executive Committee (NEC) consisting of representatives from the individual TICs/RICs and NCATS will be established to coordinate consortium-wide TIN activities. Specifically, the TIN NEC will develop and implement the operational and scientific strategic goals of the TIN, provide regular updates to the CTSA program, collaboratively engage non-CTSA stakeholders, and ensure excellence and harmonization of consortium-wide TIN activities. NCATS will appoint External Scientific Consultants to provide the TIN NEC with feedback on the overall effectiveness, impact and value of TIN activities and resources to the CTSA consortium, NCATS/NIH stakeholders and the clinical trial operations community.

NCATS will make final decisions regarding TIN consortium-wide activities, allocation of studies to TICs/RICs, and use of NCATS TIC/RIC funding to support resources provided to individual investigators and protocols.

Other committees will be established as needed to oversee daily operations of the TIN and TICs/RICs and to deliver approved resources such as Single IRB educational resources and standard agreement templates.

Application and Submission Information

This notice applies to due dates on June 21, 2022.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PAR-22-122, Limited Competition: Clinical and Translational Science Awards (CTSA) Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

R&R Budget

Applicants should request costs associated with demonstration and dissemination of resources through the Trial Innovation Network. Costs for serving as a clinical and/or data coordinating center for individual clinical trials will be provided by the trial sponsor via other funding mechanisms.

R&R Subaward Budget

Subawards are permitted but must be necessary for the demonstration and dissemination of resources through the TIN.

PHS 398 Research Plan

Specific Aims: Briefly state the specific aims of the proposed TIC indicating how it will demonstrate and disseminate highly innovative, collaborative and impactful clinical trial resources (to include capabilities, methods and expertise) to enhance the overall quality and efficiency of clinical trials conducted within the CTSA program.

Specific Aims should reflect that the trial support provided by the TIC will vary over time and with different projects and will depend on the complexity and stages of the trials in progress as well as the needs and contributions of the trial sponsors.

Research Strategy: Applications should include the following information in the subsections detailed in the SF424 (R&R) Application Guide and PAR-22-122. Any unique capabilities/experiences the proposed TIC may have in supporting certain types of trials/interventions/sites or working with vulnerable or underrepresented populations should be indicated in the Research Strategy section. Applicants should clearly indicate the capacity of the proposed TIC to support pediatric and/or geriatric-focused clinical trials.

Significance: Explain how the proposed TIC will enhance the capacity of the TIN to address roadblocks in clinical trials and accelerate the translation of novel interventions into therapies that improve health and save lives. Describe how the resources demonstrated by the proposed TIC and disseminated through the TIN will increase the overall quality and efficiency of multi-site clinical research within the CTSA network. Describe how the proposed TIC will advance clinical and translational science by participating in clinical trials as a clinical and/or data coordinating center and by disseminating clinical trial resources through the TIN.

Innovation: Describe any novel or innovative approaches the proposed TIC plans to utilize to support the development of protocols and/or execution of multi-site trials.

Applicants are encouraged to propose innovative approaches and/or functions that help facilitate the administration or conduct of clinical trials, or that enhance the quality and efficiency of multi-site clinical studies.

Approach: Describe how the proposed TIC will provide the following resources to individual CTSA investigators submitting proposals for TIN consultation:

• Study Design Planning: This resource will help investigator teams define the study goals and aims, methodology, and statistical approaches. The resource should span a continuum of interactions from short consultations to more complex meetings involving multiple stakeholders and should include assistance with more complex trial designs such as platform trials, master protocols, and adaptive trials. The Study Design Planning resource will be available to investigator teams even if a TIC is not serving as the data coordinating center for the proposed trial.
• Study Operations Planning: (Implementation, Budget, Timelines, Feasibility). This resource may involve meetings to evaluate regulatory considerations, subject recruitment, schedule of assessments, availability of study interventions, and/or other components of the proposed study. The goal is to identify potential barriers to successful study completion and to propose solutions.
• Contracting: Describe a plan for the proposed TIC to provide assistance to CTSA investigators planning to implement standard agreements (such as the Federal Demonstration – Clinical Trial Standard Agreement for federally funded studies or the Accelerated Clinical Trial Agreement for industry-funded studies) to streamline contract negotiations and expedite study start-up.
• Single IRB: Describe a plan for the proposed TIC to establish processes to educate investigators and their teams about the single IRB (SIRB) process to meet NIH and DHHS requirements for the use of a SIRB of record for multi-site research. This plan will include providing support, resources, and tools to ensure all site investigators understand how to use a SIRB at their institution throughout all phases of a multi-site study, i.e. from initial submission of the protocol for SIRB review to study closeout. It is expected that SIRBs will use the SMART IRB Authorization Agreement as the basis for reliance. NOTE that costs for a TIC SIRB acting as the reviewing IRB must be paid by the trial sponsor -the TIC award will not cover actual costs of serving as a reviewing SIRB.
• Expression of Interest: Describe a plan to work with the other TICs/RICs to develop a formal outreach from the TIN to CTSA Program hubs announcing a possible trial opportunity. The proposed Expression of Interest process is intended to provide CTSA Program hubs, their affiliates, and partners with opportunities to participate in potential trials through a TIN-developed outreach model and to create a virtual network in which any CTSA hub/affiliate/partner may act as the data coordinating center for a trial. The proposed Expression of Interest process may include requests for sites to determine feasibility of the study protocol and/or site budget, to conduct an EHR-based Cohort Assessment to assess available recruitment populations, and/or to identify local site investigators. The Expression of Interest plan in the application should include details on how Hub Liaison Teams (HLTs) will be involved in the Expression of Interest process and how non-CTSA clinical centers may be added to trials to augment participant recruitment. Principles of diversity, equity and inclusion should be applied to all processes described in the Expression of Interest plan. The Expression of Interest process should include approaches for ensuring geographic diversity of recruitment sites such as engagement with other NIH clinical trial networks, PCORnet, and/or IDeA Centers for Translational Research.
• Oversight and Regulatory: Describe plans for the proposed TIC to provide the following functions on an as needed basis:
  • Convene and support activities of Data and Safety Monitoring Boards (DSMBs).
  • Provide Regulatory Affairs functions to assist in the preparation of regulatory documents such as Investigational New Drug (IND), Investigational Device Exception (IDE) or Orphan Drug applications, to address compliance with applicable domestic and international human subjects/clinical trial policies, and to remediate issues of non-compliance with regulatory policies and agencies.
  • Engage with the FDA to support regulatory science for innovative trial designs such as adaptive designs, serial “n of 1” design, or other approaches to small populations, which could overcome some of the challenges in evaluating interventions for rare diseases.
• Protocol and Consent Development: Describe a plan for the proposed TIC to establish a Protocol Development Team that will work with trials that plan to utilize a TIC as a data or clinical coordinating center. The Protocol and Consent Development plan should include details of interactions with the study Principal Investigators, collaborating investigators and study funders to refine and finalize the protocols, consent forms, and associated documents and to prepare for SIRB submission. Plans for obtaining and including participant perspectives on trial design and relevant trial documents such as informed consent forms should be included in the Protocol and Consent Development plan.

The Approach section of the Research Strategy may contain descriptions of other plans for how the proposed TIC may support investigators and/or low-resource clinical settings to improve the efficiency, quality, and likelihood of successful implementation of multi-site studies. If so, the description in the application should include details of the proposed interactions with trial leadership teams, other TICs/RICs, and NIH staff to identify inefficiencies and barriers throughout the lifecycle of the multi-site study and to implement innovative process improvements while maintaining study quality and participant safety.

In the Approach section of the Research Strategy, applicants should describe plans to provide skills enhancement opportunities for investigators and clinical research personnel at various career stages/experience levels. These skills enhancement opportunities may include dissemination of common standards in clinical trial management such as Good Clinical Practice guidelines and FAIR and TRUST data science principles or “hands-on” demonstration of operational methods and tools. Skills enhancement opportunities may be piloted at an individual TIC and further developed/refined in collaboration with NCATS and the other TICs/RICs.

The Approach section must contain a clear description of the experience of the proposed TIC in supporting clinical trials as well as an estimate of the proposed TIC’s capacity in terms of type and number of multi-site trials that can be initiated and implemented in the next funding period.

Additional Research Strategy Elements Required for the Parent Funding Opportunity Announcement, PAR-22-122

Program Director/Principal Investigator: Without duplicating information in the biosketches, describe how the PD/PI and other designated senior/key personnel will contribute to the proposed TIC’s capacity to function as a clinical and/or data coordinating center and will facilitate demonstration of operational innovations and dissemination of TIN resources.

Addressing a systemic barrier in clinical and translational science: Describe how the resources demonstrated and disseminated by the proposed TIC will address CTSA Program Strategic Goals. Describe a vision for how the proposed TIC in collaboration with the other TICS/RICS as part of the NCATS TIN will address CTSA Program Strategic Goals.

NOTE that TICs are expected to specifically contribute to CTSA Program Strategic Goals 1, 2, 3, 4 and 5:

1. Advance clinical and translational science: develop, demonstrate and disseminate scientific and operational innovations that improve the efficiency and effectiveness of clinical translation from identification to first-in-human studies to medical practice implementation to community health dissemination.
2. Promote partnerships and collaborations to facilitate and accelerate translational research projects locally, regionally and nationally.
3. Create, provide, and disseminate innovative research programs and partnerships across institutions and communities to address health disparities and deliver the benefits of translational science to all.
4. Create and implement scientific and operational innovations that increase the quality, safety, efficiency, effectiveness and informativeness of clinical research.
5. Provide a national resource for the rapid response to urgent public health needs.

Needs Assessment: Provide a needs assessment that includes a review of CTSA participation in large, multi-site clinical studies, resources that are required for or facilitate CTSA participation in large, multi-site clinical trials, operational inefficiencies that delay trial start-up and/or recruitment, and clinical trial management and operational processes that are not currently harmonized across the CTSA consortium. Provide a rationale for why continued dissemination of TIN resources has the likelihood to be impactful for the CTSA consortium. Provide a description of how new resources and/or operational innovations, once demonstrated and disseminated, will be likely to have sustained impact on the implementation of multi-site clinical studies within the CTSA consortium.

Evidence that the proposed resource is ready for use and dissemination: For existing TIN resources/processes, provide a strategy for determining that the TIN resource/process has led to a measurable impact in the implementation and/or completion of multi-site clinical studies conducted within the CTSA consortium.

Strategy for generating evidence for resources that are not evidence-based:

For operational innovations that are being refined/adapted by the proposed TIC, provide a plan to test and validate these operational innovations in clinical trials in which the proposed TIC serves as a clinical and/or data coordinating center. Operational innovations could include testing methods to rapidly identify and enroll participants for clinical trials, methods to reach and enroll diverse and underserved populations in clinical research, and/or methods for including the patient’s perspective in a clinical research study. When applicable, plans for evaluating the effects of the operational innovations on specific components (site activation, regulatory approvals, contract execution, acquisition of study products/interventions, etc.) of the trial start-up process should be described.

Dissemination Plan: In the Dissemination Plan section of the Research Strategy, describe plans for the proposed TIC in collaboration with other TICs/RICs, to establish a process to develop an electronic portal for managing requests for TIN consultations and resources. The TIN consultation process should be designed to help CTSA investigators develop proposals into protocols, enhance study operations, and/or improve recruitment and retention. The Dissemination Plan for consultations in the application should include information on: development and maintenance of TIN SOPs, a data system to manage proposal submissions, interactions with the CTSA Hub liaison teams (HLT) to ensure prompt submissions and responses to requests for TIN resources, and plans for managing conflicts of interest.

Plans for disseminating any special group expertise or unique strengths of the proposed TIC such as tools or approaches the proposed TIC may offer to the collaborative effort (e.g., experience in clinical trial collaborations with NIH ICs, industry partners, and/or patient groups; experience in supporting FDA-regulated trials; experience with risk-based and/or remote site monitoring) or unique experiences the proposed TIC may have such as providing skills development opportunities for workforce development should be described in this section of the application.

Evaluation Plan: In the Evaluation Plan section of the Research Strategy, applicants must provide an estimate of the proposed TIC’s capacity to initiate and implement multi-site clinical studies in the next funding period and detail the milestones and metrics that will be used to monitor progress and assess performance at all stages of the life cycle of a multi-site clinical study. Applicants should describe plans to track trial progress/monitor data quality and to communicate with the trial investigators and sponsors when the proposed TIC serves as a clinical and/or data coordinating center for a multi-site clinical study.

The vision for an overall Evaluation Plan of how the TICs/RICs will collaborate to disseminate the specified TIN resources (study design planning, study operations planning, contracting, single IRB, Expression of Interest) to the CTSA consortium should be described in this section of the application.

Management Plan: In the Management Plan section of the Research Strategy, describe how tasks will be delegated within the TIC and how teams within the TIC will communicate when the proposed TIC serves as a clinical and/or data coordinating center for a multi-site clinical study.

Describe a plan to collaborate with the other TICs/RICs and the CTSA Program hubs when specific TIN resources are disseminated to the CTSA consortium. Describe plans for integration of the proposed TIC into the coordination plan for the TIN and the vision for how the proposed TIC will contribute to the TIN Network Executive Committee (NEC).

Sustainability Plan: In the Sustainability Plan section of the Research Strategy, describe how the proposed TIC will maintain its capacity to function as a clinical and/or data coordinating center after NIH funding ends. Describe how the proposed TIC will continue to disseminate operational innovations and provide skills enhancement opportunities after NIH funding ends. Plans for increasing capacity on a fee-per-service basis should more sponsors and investigators than initially anticipated express interest in working with the TIC may be described in this section.

Applicants may describe a vision for how the proposed TIC in collaboration with the other TICs/RICs can maintain and disseminate TIN resources with broad applicability after NIH funding ends.

External Scientific Consultants: Applicants should describe plans for the appointment of External Scientific Consultants to provide advice and comments to the proposed TIC about its strengths and weaknesses as a clinical and/or data coordinating center, the potential value and utility of any operational innovations that the proposed TIC is refining or adapting for dissemination as a TIN resource, the potential value and utility of any skills enhancement opportunities that the proposed TIC is piloting, and the efficiency and effectiveness of the proposed TIC in demonstrating and disseminating TIN resources. NOTE that NCATS will appoint External Scientific Consultants to provide advice to the TIN NEC on the overall effectiveness, impact and value of the combined TIC/RIC activities and resources at the network level to the CTSA consortium, NCATS/NIH stakeholders and the clinical trial operations community.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Application and Submission Information

This notice applies to application receipt dates on June 21, 2022.

Submit applications for this initiative using the following funding opportunity announcement (FOA).

• PAR-22-122, Limited Competition: Clinical and Translational Science Awards (CTSA) Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (U24 Clinical Trials Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-TR-22-021” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

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