A severity-anchored, patient-reported outcome framework for clinical trials in post-stroke dysphagia.

BACKGROUND

Post-stroke dysphagia is common and is associated with aspiration pneumonia, malnutrition, longer hospitalization, and reduced quality of life. Trials evaluating interventions for post-stroke dysphagia face persistent challenges in selecting endpoints that are both patient-centered and methodologically robust.

OBJECTIVES

To derive and justify a patient-reported outcome (PRO) endpoint for stroke-related dysphagia that supports clinically meaningful interpretation, statistical efficiency, and alignment with regulatory expectations.

METHODS

We synthesized regulatory guidance, outcomes-research standards, and stroke-specific evidence to develop a dichotomous, status-based PRO responder endpoint at 90 days post-stroke that integrates swallowing-specific quality of life (SWAL-QOL) and global health-related quality of life (EuroQol-5D; EQ-5D). Responder definitions were calibrated to baseline dysphagia severity using swallowing-relevant National Institutes of Health Stroke Scale (NIHSS) subcomponents assessed in the early post-acute period. Monte Carlo simulations (10,000 simulated patients with post-stroke dysphagia) compared performance of the combined responder endpoint versus (i) continuous SWAL-QOL and (ii) utility-weighted modified Rankin Scale (UW-mRS) analyses under clinically realistic severity distributions and treatment effects. Sample size requirements were estimated for individually randomized and stepped-wedge designs.

RESULTS

Severity-anchored responder endpoints were more statistically efficient and more interpretable than continuous or change-based analyses in heterogeneous acute stroke populations. In simulation, combined SWAL-QOL + EQ-5D responder rates increased from 42.7% (control) to 66.2% (treatment), an absolute difference of 23.5% (odds ratio 2.58, 95% CI 2.38-2.81; number needed to treat ≈ 4-5), with the largest effects in moderate and severe dysphagia. In contrast, mean SWAL-QOL improved by 8.3 points (near or below commonly cited minimal clinically important difference thresholds), and mean UW-mRS improved by 0.017, indicating limited sensitivity of global disability measures.

CONCLUSION

A severity-calibrated, dichotomous PRO responder endpoint combining SWAL-QOL and EQ-5D provides a patient-centered, statistically efficient, and methodologically robust framework for evaluating therapeutic interventions in post-stroke dysphagia.