Risk of selection bias assessment in the NINDS rt‑PA stroke study
Abstract
The NINDS rt-PA Stroke Study is frequently cited in support of alteplase for acute ischemic stroke within
3 h of symptom onset. Multiple post-hoc reanalyses of this trial have been published to adjust for a baseline imbalance
in stroke severity. We performed a risk of selection bias assessment and reanalyzed trial data to determine if the
etiology of this baseline imbalance was more likely due to random chance or randomization errors. A risk of selection bias assessment was conducted using signaling questions from the Cochrane Risk of
Bias 2 (ROB 2) tool. Four sensitivity analyses were conducted on the trial data based on the randomization process:
assessment of imbalances in allocation in unique strata; adherence to a pre-specified restriction on randomization
between time strata at each randomization center; assessment of differences in baseline computed tomography (CT)
results in unique strata; and comparison of baseline characteristics between allocation groups within each time strata.
A multivariable logistic regression model was used to compare reported treatment effects with revised treatment
effects after adjustment of baseline imbalances identified in the sensitivity analyses.