Abstract 114: Biomarkers for Patient Selection Improve Stroke Rehabilitation Trial Efficiency

Abstract

There is high inter-individual variability in recovery after stroke, which reduces statistical power in rehabilitation trials. This could be addressed by using biomarkers for patient selection. Corticospinal tract function assessed with transcranial magnetic stimulation (TMS) is a candidate biomarker for trials aiming to improve upper-limb motor recovery. Patients in whom TMS can elicit motor evoked potentials (MEPs) have a functionally intact lateral corticospinal tract and better motor recovery. We used an existing data set to estimate the sample sizes required to detect rehabilitation benefits on upper-limb motor performance 90 days after stroke. Baseline clinical assessments were made and MEP status of the paretic upper-limb determined within 7 days post-stroke. Upper-limb Fugl-Meyer (UE-FM) and Action Research Arm Test (ARAT) scores were obtained 90 days after stroke. Analyses were carried out for the full sample, and repeated for the MEP+ subset. Population estimates of the UE-FM and ARAT scores 90 days post-stroke were used to calculate the sample sizes required to detect clinically meaningful treatment effects of 7 points on the UE-FM and ARAT scores. Baseline and 90-day assessments were completed by 207 patients (103 women, mean 70.6 SD 15.1 years). The full sample and MEP+ subset (n=177) had similar demographic and baseline clinical characteristics. The estimated required sample sizes to detect treatment effects for MEP+ patients were only 27-29% of those for the full sample of patients. The estimated percentage of patients who are MEP+ was 85.5% (95%CI 81.2%-89.9%). Biomarkers could be used to enrich samples for stroke rehabilitation trials. Selecting patients on the basis of MEP status reduces variance, thereby reducing required sample size by around 75% without significantly limiting the pool of participants. Using biomarkers for patient selection could markedly increase rehabilitation trial sensitivity and efficiency, with associated decreases in costs and time required for completion.