Introduction: Lasagna’s Law, that the prevalence of a disease falls to 10% of your estimate the day you start recruitment, is relevant for stroke rehab trials. Data describing the problem are limited for very early trials (within 30 days) since most trials focus on more chronic survivors and moderate upper-extremity (UE) impairment (NIHSS motor arm > 0). Very early trials are important for rehab because animal data suggest very early intervention may improve recovery. We thus provide estimates on barriers to recruitment for very early rehabilitation trials in the US.
Methods: We used screening data for the Phase II Critical Periods After Stroke Study RCT, designed to identify when after stroke patients are most responsive to motor training. Starting Aug 2014, 893 patients eventually admitted to inpatient rehab were screened (5 ±2 days post stroke).
Results: We enrolled 4.3% of those screened, at 15.5 ±4.9 days post stroke. Participants had ischemic/hemorrhagic stroke within 28d, and moderate UE impairment (NIHSS motor arm > 0 and manual muscle test score >2- on shoulder flexion/abduction). The largest % were excluded for being “too mild” (35.7%, NIHSS motor arm = 0), or “too late” (18%, unable to receive first study-related treatment < 30 days of stroke). A smaller percentage were “too severe” (3.6%, UE motor assessment scale <3, or dense sensory loss). Another subset were excluded for medical reasons (19.7%, prior/non-motor stroke, cognition, neglect, ataxia), and a smaller subset for other reasons (17.8%, non-English speakers, early discharge, age < 21). Additional UE motor assessment in a subset of the “too mild” group revealed motor deficit (Action Research Arm Test score = 47.7 ±12, max = 57, MCID = 5.7) in spite of their NIHSS motor arm score = 0. Thus, some individuals are excluded from trials because the NIHSS misses UE motor impairment.
Conclusion: Frequent barriers to recruitment for inpatient rehab trials include persistent but too mild UE motor impairment and delayed admission to inpatient rehab. For early intervention studies, screening and treatment must begin in the acute hospital setting. Further, there is a patient subset whose motor impairment persists, but is too mild for most trials. These mildly affected individuals warrant more investigation.