Abstract TP334: Building Better Controls: Methodological Innovation in Post-Stroke Upper Extremity Rehabilitation Trials

Introduction: The Critical Periods After Stroke Study (CPASS; n=72) was a Phase II RCT testing 20 additional hours of individualized upper extremity (UE) therapy within 1-year post-stroke at acute (<30d), subacute (2–3mo), and chronic (6–9mo) timepoints. Compared with controls, subacute participants achieved Action Research Arm Test (ARAT) gains exceeding the minimal clinically important difference (p=0.009), while acute participants showed smaller but significant improvement (p=0.043). The chronic group showed no significant gains, suggesting a critical recovery period. CPASS used a usual care control. An intensity-matched active control is needed to clarify whether recovery reflects timing, therapy content, or both. This study outlines the methodological decisions guiding the Optimizing Post-Stroke Intervention Methods for Recovery (OPTIM-R) trial, which introduces a standardized, equal-intensity active control (figure 1) . Hypothesis: Individualized UE rehabilitation will produce superior 1-year ARAT outcomes relative to conventional standardized therapy. Methods: OPTIM-R is a prospective superiority trial comparing the CPASS subacute cohort with a newly recruited active control group. Key design features include aligning assessments and outcomes with CPASS to ensure comparability while reducing participant burden, initiating therapy within 0–3 months to capture acute and subacute participants, and excluding CPASS’s individualized elements to isolate treatment effects. Strategic design choices ensured fidelity to CPASS while making the intervention reproducible and distinct from the experimental arms. The primary outcome is 1-year ARAT scores, analyzed with generalized estimating equations consistent with CPASS. 24 participants meeting CPASS inclusion/exclusion criteria will be enrolled using stratified methods to balance the new cohort, chosen instead of adaptive randomization since the active control does not include multiple groups. Conclusion: By establishing an intensity-matched active control, OPTIM-R addresses the methodological question raised by CPASS, enabling direct comparison of individualized therapy with equal-intensity conventional care. This design clarifies whether personalization of UE therapy provides added benefit when delivered at the same post-stroke time point. By emphasizing fidelity, feasibility, and reproducibility, OPTIM-R advances methodological rigor and offers a replicable framework for future stroke rehabilitation trials.