Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or "hybrid" trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

Approaches for enhancing the informativeness and quality of clinical trials: Innovations and principles for implementing multicenter trials from the Trial Innovation Network.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Development, implementation, and dissemination of operational innovations across the trial innovation network.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

The Trial Innovation Network Liaison Team: building a national clinical and translational community of practice.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Using gamification to enhance clinical trial start-up activities.

Background: The Trial Innovation Network (TIN) is a collaborative initiative within the National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Awards (CTSA) Program. To improve and innovate the conduct of clinical trials, it is exploring the uses of gamification to better engage the trial workforce and improve the efficiencies of trial activities. The gamification structures described in this article are part of a TIN website gamification toolkit, available online to the clinical trial scientific community. Methods: The game designers used existing electronic trial platforms to gamify the tasks required to meet trial start-up timelines to create friendly competitions. Key indicators and familiar metrics were mapped to scoreboards. Webinars were organized to share and applaud trial and game performance. Results: Game scores were significantly associated with an increase in achieving start-up milestones in activation, institutional review board (IRB) submission, and IRB approval times, indicating the probability of completing site activation faster by using games. Overall game enjoyment and feelings that the game did not apply too much pressure appeared to be an important moderator of performance in one trial but had little effect on performance in a second. Conclusion: This retrospective examination of available data from gaming experiences may be a first-of-kind use in clinical trials. There are signals that gaming may accelerate performance and increase enjoyment during the start-up phase of a trial. Isolating the effect of gamification on trial outcomes will depend on a larger sampling from future trials, using well-defined, hypothesis-driven statistical analysis plans.

Sharing data among clinical trials of therapeutics in COVID-19: Barriers and facilitators to collaborating in a crisis.

Background: The Clinical and Translational Science Award Program (CTSA) Trial Innovation Network (TIN) was launched in 2016 to increase the efficiency and effectiveness of multisite trials by supporting the development of national infrastructure. With the advent of the COVID-19 pandemic, it was therefore well-positioned to support clinical trial collaboration. The TIN was leveraged to support two initiatives: (1) to create and evaluate a mechanism for coordinating Data and Safety Monitoring Board (DSMB) activities among multiple ongoing trials of the same therapeutic agents, and (2) to share data across clinical trials so that smaller, likely underpowered studies, could be combined to produce meaningful and actionable data through pooled analyses. The success of these initiatives was understood to be dependent upon the willingness of investigators, study teams, and US National Institutes of Health research networks to collaborate and share information. Methods: To inform these two initiatives, we conducted semistructured interviews with members of CTSA hubs and clinical research stakeholders that probed barriers and facilitators to collaboration. Thematic analysis identified topics relevant across institutions, individuals, and DSMBs. Results: The DSMB coordination initiative was viewed as less controversial, while the data pooling initiative was seen as complex because of its potential impact on publication, authorship, and the rewards of discovery. Barriers related to resources, centralization, and technical work were significant, but interviewees suggested these could be handled by the provision of central funding and supportive frameworks. The more intractable findings were related to issues around credit and ownership of data. Conclusion: Based on our interviews, we conclude with nine recommended actions that can be implemented to support collaboration.

Response of the trial innovation network to the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic. METHODS: The TIN's three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic's rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned. RESULTS: The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement. CONCLUSIONS: Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.

A collaborative, academic approach to optimizing the national clinical research infrastructure: The first year of the Trial Innovation Network.

Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science (NCATS) -sponsored CTSA program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA Program and other NIH Institutes and Centers (ICs) that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN's mission is to execute high quality trials in a quick, cost-efficient manner. The TIN awardees are composed of: three Trial Innovation Centers (TICs), the Recruitment Innovation Center (RIC), and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) IRB system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH ICs across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.