Objective: To characterize feasibility and scientific rigor of a decentralized (DCT) Phase 3 trial in essential tremor (ET), emphasizing diagnostic standardization, real-world population access, centralized control, and real-time data integrity.

Background: ET affects ~7 million Americans yet research participation remains limited by distance to specialty centers, mobility challenges, and visit burden. Traditional trials concentrate enrollment at tertiary centers, restricting access and introducing inter-site variability. Essential3 evaluated ulixacaltamide in ET using a DCT model designed to enhance rigor through centralized expert oversight, ecologically valid assessments, and a unified multi-study protocol.

Method: Essential3 pivotal Study 1 (parallel-group) and Study 2 (randomized withdrawal) were conducted concurrently under a single randomized, double-blind, placebo-controlled protocol with identical screening and assessments, enabling valid cross-study comparisons from one population. A Central Coordinating Site with 3 fellowship-trained movement disorder specialist PIs and 44 sub-investigators coordinated execution under standardized procedures, reducing inter-site variability. Assessments (TETRAS-ADL, C/PGI) were conducted with participants at home, minimizing potential bias from clinic-based assessment. Independent Eligibility Review Committee of movement disorder neurologists reviewed video-recorded exams to confirm ET diagnosis, exceeding typical site-based confirmation. Real-time data entry enabled site and sponsor oversight, including daily review of AEs, lab alerts, and data completeness.

Results: Over 2,000 participants were screened nationwide, with 711 randomized, enabling broad representation of adults with long-standing ET (~30 yrs), on concomitant ET meds, and without access to specialty centers. Two studies conducted in parallel accelerated time to regulatory submission.

Conclusion: Essential3 demonstrates a DCT Phase 3 neurology trial is feasible and the DCT model enhanced rigor: centralized expert review standardized eligibility; complementary designs under one protocol enabled cross-study comparisons; home-based assessment increased ecological validity; centralized coordination reduced variability; and real-time monitoring ensured data completeness and oversight. This provides a scalable framework for future neurology trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/framework-for-future-neurology-trials-enhanced-scientific-rigor-through-innovative-decentralized-trial-methodology/