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.

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.

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.

Percutaneous perfusion monitoring for the detection of hemodialysis induced cardiovascular injury.

INTRODUCTION: The safe delivery of hemodialysis (HD) faces dual challenges; the accurate detection of systemic circulatory stress producing cardiovascular (CV) injury, and the ability to enable effective preemptive intervention for such injury. We performed a pilot study to examine the capability of a new noninvasive, real-time monitoring system to detect the deleterious effects of HD on CV stability. METHODS: Eight patients were evaluated with echocardiography prior to the initiation of HD and again at peak HD stress. Continuous CV physiologic monitoring was performed throughout using oximeter-based pulse waveform analysis (CVInsight® Monitoring System, Intelomed, Inc., Warrendale, PA, USA). Longitudinal strain (LS) values for 12 left ventricular segments were generated using speckle-tracking software (EchoPac, GE), to assess the presence of HD-induced regional wall motion abnormalities (RWMA), indicative of myocardial stunning. FINDINGS: A reduction in pulse strength (PS) of ≥40% detected by CVI was associated with the development of RWMA (P = 0.005). This reduction occurred in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no significant reduction in PS nor evidence of myocardial stunning. In subjects with cardiac stunning, the decrease in PS was evident early during HD, 11.49 ± 10 minutes into HD treatment, prior to the detection of RWMA, which were assessed at peak HD stress, mean 210 ± 16.43 minutes into HD treatment. DISCUSSION: Percutaneous perfusion monitoring, using pulse wave analysis, appears to be useful in identifying circulatory stress during HD and predicting the development of HD-induced myocardial stunning with a lead time long enough to consider timely intervention.

A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network.

BACKGROUND: Clinical trial networks (CTNs) were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. PURPOSE: In 2005, the National Institute on Drug Abuse (NIDA) CTN transitioned from a distributed data management model to a centralized informatics infrastructure to support the network's trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. METHODS: During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. RESULTS: We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%-1.0% before centralization to 0.01-0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. LIMITATIONS: A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. CONCLUSIONS: The identified informatics components provide the information and infrastructure needed for our clinical trial network. Post centralization data management operations are more efficient and less costly, with higher data quality.