Well-conducted randomized trials are considered the best method of providing evidence about the safety and efficacy of treatments to improve health. Each year, NIH Institutes and Centers spend an estimated $3-4 billion supporting clinical trial activities. These activities require high-level understanding of human biology, of manufacturing and pre-clinical research, and of regulatory requirements. The process of translating a new therapeutic from discovery to practice can be robust, but … at the same time is long and expensive – and despite the challenges inherent in complex, multi-disciplinary research sometimes too long and too expensive.
The National Center for Advancing Translational Sciences (NCATS) was established to catalyze a transformation in the way health interventions are developed and to bring more treatments to more patients more efficiently and quickly. To expedite clinical trial processes from start-up to close-out, NCATS established the NCATS Trial Innovation Network (TIN). The Network is a collaborative initiative among three Trial Innovation Centers (TICs), a Recruitment Innovation Center (RIC), and the Clinical and Translational Science Award (CTSA) program hubs. The goal of the TIN is to conduct high quality multi-site clinical trials faster and more cost-efficiently through the provision of services such as single IRB and standard contract agreements or by helping investigators develop robust recruitment and retention plans. In addition, the TIN serves as a national laboratory to study, understand and innovate the process of conducting clinical trials and accelerate the translation of novel interventions into life-saving therapies. To test an innovative approach to improve clinical trials, TIN awardees embed an operational hypothesis into each trial or study they support (i.e., determining how to best collect data from a mobile device or how to reach and recruit populations, including underserved populations) to determine which innovations speed translation.
What are the components of the Trial Innovation Network and what do they do?
There are three main components of the Trial Innovation Network (TIN).
- Trial Innovation Centers (TICs)
Three Trial Innovation Centers (TICs) were funded by NCATS. The TICs aim to develop, demonstrate, and disseminate innovative ways to increase the quality and efficiency of multi-site clinical research. The TICs provide collaborative support for a broad range of multi-site clinical studies that include trials across the human life span, trials for diagnostic testing or development of therapeutics such as drugs, biologics, and devices, as well as behavioral interventions.
The TICs provide services that range from discrete services (e.g., central IRB) to comprehensive services (e.g., serving as the data coordination center) for trials supported by the TIN.
2.Recruitment Innovation Center
The Recruitment Innovation Center (RIC) aims to become a successful, evidence-based Center in recruitment and retention strategies to improve both the quality of future clinical trials and to raise awareness of the value of research, thereby increasing trial enrollment and health outcomes across America. The RIC develops, demonstrates, and disseminates patient-centered tools and training modules, and provides services to enhance participant engagement, recruitment, and retention, with Electronic Health Record cohort assessments to identify CTSA hubs with potential study participants. In addition, the RIC is maintaining a repository of “Best Practices” in engagement, recruitment, and retention. Collectively, these efforts are intended to facilitate meaningful engagement and to address barriers that limit the participation of underrepresented and marginalized persons (including aging, rural, and racial/ethnic minority communities) in clinical studies and trials.
- CTSA Program hubs
The CTSA Program Hubs along with other clinical research institutions form the clinical centers of the TIN. They use their experience and knowledge of the local environment to facilitate collaboration with the TIN in developing and disseminating clinical trial innovations as well as facilitating TIN-CTSA services locally. They are available to act as clinical sites for multi-center studies.
What services does the Trial Innovation Network offer?
The TIN offers a variety of services for investigators. Investigators do not need to be at a CTSA institution to request TIN support.
Trial Innovation Network Consultations:
All proposals submitted to the Network will receive an Initial Consultation to discuss a collaboration with the TIN. Investigators may wish to have one of the TICs act as the data coordination center / clinical coordinating center and utilize all TIN services for their study. In this situation, the TIC will be included in the grant application to an individual NIH Institute or Center (IC). To do this, the investigator should submit a request for initial consultation six months before the grant application due date to allow adequate time to prepare the application for submission.
The TIN offers many services to support clinical trials. Requests for these services should be made 60 days before the application is due. These services may also be requested after an application is funded.
- Operationalize Standard Agreements: The complexity of contract negotiations can be a major barrier to timely study start-up. This service provides recommendations on how to use either the FDP-CTSA agreement for federal funded studies or the ACTA agreement for studies funded by industry. Standard Agreements can potentially be used by each of the participating institutions in a multi-site study, particularly if the process is started before initiation of the contracting process.
- Operationalize Central IRB: The TIN has established three Central IRBs (CIRBs), which are based on the SMART IRB Authorization Agreement to provide CIRB services to a funded multi-center clinical trial. For each study, the Trial Innovation Network CIRB will also provide resources, tools, and a web-based platform (IRB Reliance Exchange or IREx) to operationalize the CIRB. The goal is to ensure all site investigators understand the process for initiating the use of a CIRB at their local institution, as well as how to submit and report to the CIRB from initial submission to study closeout.
- Recruitment Plan & Feasibility Assessment: An effective recruitment plan includes strategies to identify and engage specific population(s) of relevance for a trial, including how to communicate and market a study to engage potential participants and meet realistic enrollment and retention goals. The recruitment plan service includes providing advice and recommendations on recruitment strategies.
- Community Engagement Studio. A Community Engagement Studio is a consultative method that allows meaningful involvement of diverse groups of stakeholders in the planning and implementation of research. The Studios can be used to facilitate project-specific input including guidance and recommendations on identifying and addressing barriers to participation and how to develop or refine recruitment materials and messages.
- EHR-Based Cohort Assessment. This TIN service can help investigators to consider ways that Electronic Health Record (EHR) data may be leveraged to inform study design and potential site selection. This includes expert clinical and technical review of a study’s recruitment goal and high-level assessment of computable phenotyping. Funded projects may also request and receive the support required to organize the distribution of phenotype algorithms to potential CTSA hubs, with collation of results.
- Efficacy-to-Effectiveness (E2E) Trial Design (a focus area for initial consultation). An E2E Consultation will allow the study team to think through the evidence required by various stakeholders, and prospectively design a study that allows regulators, payers, patients, healthcare providers and physicians to make informed decisions.
How can Trial Innovation Network services be utilized?
First, investigators should communicate with their local CTSA PI and Trial Innovation Network Liaison Team and obtain a letter of support from a CTSA Principal Investigator. The study investigator does not need to be at a central CTSA hub. (Investigators who are not affiliated with a CTSA institution are not required to obtain CTSA PI approval.) On this page you will find contact information for the CTSA Program Hubs and other clinical research institutions that will facilitate collaboration with the TIN through the Trial Innovation Network Liaison Teams. Second, investigators should complete a proposal intake form at the website www.trialinnovationnetwork.org. After the proposal is submitted to the TIN, the proposal will be assigned to one of the TICs and/or RIC and the study investigator will be contacted within approximately five business days. The assigned TIC and/or RIC will work with the study investigator to complete an initial consultation. The initial consultation may last more than one session if the proposal is accepted for support and may lead to a comprehensive consultation.
How often is the Trial Innovation Network being used?
In less than 2 years since inception, the TIN has received 116 requests for support from 39 different CTSA institutions. Of these, 98 are receiving or have received support from the TIN and the proposals were associated with twelve different NIH I/Cs.
In conclusion, The TIN exemplifies NCATS’ role in promoting innovation. The network focuses on new approaches to operationalize clinical trials, finish studies on time and within budget, and ways to leverage the expertise, diversity and broad reach of the NCATS CTSA Program.