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

90 Novel approach for childhood Sjögren’s Disease therapies: multistakeholder design of a series of N-of-1 trials

OBJECTIVES/GOALS: Childhood Sjögren’s disease (cSD) is a rare autoimmune disease. Despite the profound impact on children and their families, pediatric-specific clinical trials to inform therapeutic strategies in cSD are lacking. In 2022 we participated in the Trial Innovation Network (TIN) Design Lab with the purpose of designing a series of N-of-1 trials for cSD. METHODS/STUDY POPULATION: New medications have the potential to be safe/effective treatments for cSD but must be evaluated in randomized trials. To overcome limitations of traditional parallel-group designs given the rarity of cSD, we developed an N-of-1 trial approach. Our proposal was selected by the Tufts TIN Design Lab. The Design Lab multi-stakeholder process involved parents of and patients with cSD, pediatric and adult rheumatologists, and experts in clinical trial design and outcomes. We engaged all stakeholders in protocol development to maximize the impact of the proposed approach on clinical care, ensure a successful recruitment plan, and inform the choice of endpoints as there are no widely accepted cSD outcome measures to determine treatment efficacy. RESULTS/ANTICIPATED RESULTS: Using the Design Lab methodology, we clarified the N-of-1 study goals and engaged in an iterative process to develop a “briefing book” that ensured a sound premise for our study. We reviewed and accumulated published literature to support our focus on mucosal/glandular manifestations, identified potential interventions to be used in the N-of-1 trials, and enumerated possible outcomes, including outcomes important to patient/parents. This work culminated in a full-day Design Lab event that included multiple stakeholders who provided expertise from different perspectives on the full drug development pathway. Study design feedback focused on three specific areas. 1) Inclusion and exclusion criteria; 2) Identification of outcome measures; 3) Treatment and washout periods. DISCUSSION/SIGNIFICANCE: To address the critical need and move treatment of cSD forward, we are designing a prototype N-of-1 trial in children with rheumatic disease. We will continue to engage stakeholders by using a series of Delphi surveys and an in-person meeting to create composite outcome measures to test cSD therapies in personalized trials

555 Design Lab Methodology Supports Innovation in Clinical Trials

OBJECTIVES/GOALS: Since 2017, we have used the Design Lab methodology to support investigators taking innovative approaches to clinical effectiveness trial design. To date we have held 12 Design Labs and this year we are creating a handbook that will support dissemination of this approach across the Clinical and Translational Science Award consortium. METHODS/STUDY POPULATION: The Clinical Trial Design Lab brings together a multi-stakeholder group to consider innovative and impactful clinical trial designs. An investigative team is selected from a competitive pool of applicants, after which expert-led consultations support the investigator team to think about evidence generation in the context of the full treatment development pathway. Teams map the stakeholders at each step of this pathway (e.g. clinicians, patients, researchers, funders, industry experts, policy experts, regulatory experts, payers) and consider innovative design solutions. These consultations prepare investigators for an event that involves all stakeholders in a structured and facilitated discussion about trial designs that generate the best evidence and increase potential for health impact. RESULTS/ANTICIPATED RESULTS: The result of our work will be a set of Design Lab principles, a handbook with templates that support stakeholder mapping and structured discussions, and educational resources to accompany the handbook. The work is supported by a literature review that characterizes the multi-component processes included in the Design Lab, situates them within the larger context of team science interventions, and lays groundwork for the development of process metrics and impact evaluation criteria to assess the Design Lab method. In this poster presentation, we will share our multi-component broadly engaged team science approach, provide a brief outline of the principles and educational resources, and include an early version of the evaluation criteria. DISCUSSION/SIGNIFICANCE: Broadly engaged team science supports innovative thinking about study design and is especially important in the development of clinical trials. We have grown the Design Lab program of work over the past seven years and are now able to characterize our team science methodology and support others to use this approach to innovate for health impact

A Useful and Sustainable Role for N-of-1 Trials in the Healthcare Ecosystem.

Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient. However, to date, these trials are rarely done outside of research settings and have not been integrated into general care where they could offer substantial benefit. Designating this classical, N-of-1 trial design as type 1, there also are new and evolving uses of N-of-1 trials that we designate as type 2. In these, rather than focusing on optimizing treatment for chronic diseases when multiple approved choices are available, as is typical of type 1, a type 2 N-of-1 trial tests treatments designed specifically for a patient with a rare disease, to facilitate personalized medicine. While the aims differ, both types face the challenge of collecting individual-patient evidence using standard, trusted, widely accepted methods. To fulfill their potential for producing both clinical and research benefits, and to be available for wide use, N-of-1 trials will have to fit into the current healthcare ecosystem. This will require generalizable and accepted processes, platforms, methods, and standards. This also will require sustainable value-based arrangements among key stakeholders. In this article, we review opportunities, stakeholders, issues, and possible approaches that could support general use of N-of-1 trials and deliver benefit to patients and the healthcare enterprise. To assess and expand the benefits of N-of-1 trials, we propose multistakeholder meetings, workshops, and the generation of methods, standards, and platforms that would support wider availability and the value of N-of-1 trials

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

A Useful and Sustainable Role for N‐of‐1 Trials in the Healthcare Ecosystem

Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient. However, to date, these trials are rarely done outside of research settings and have not been integrated into general care where they could offer substantial benefit. Designating this classical, N-of-1 trial design as type 1, there also are new and evolving uses of N-of-1 trials that we designate as type 2. In these, rather than focusing on optimizing treatment for chronic diseases when multiple approved choices are available, as is typical of type 1, a type 2 N-of-1 trial tests treatments designed specifically for a patient with a rare disease, to facilitate personalized medicine. While the aims differ, both types face the challenge of collecting individual-patient evidence using standard, trusted, widely accepted methods. To fulfill their potential for producing both clinical and research benefits, and to be available for wide use, N-of-1 trials will have to fit into the current healthcare ecosystem. This will require generalizable and accepted processes, platforms, methods, and standards. This also will require sustainable value-based arrangements among key stakeholders. In this article, we review opportunities, stakeholders, issues, and possible approaches that could support general use of N-of-1 trials and deliver benefit to patients and the healthcare enterprise. To assess and expand the benefits of N-of-1 trials, we propose multistakeholder meetings, workshops, and the generation of methods, standards, and platforms that would support wider availability and the value of N-of-1 trials