Establishing Minimally Clinically Important Differences for the Orthostatic Hypotension Questionnaire (OHQ)

ABSTRACT Purpose Establish the minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ). Background Neurogenic orthostatic hypotension (nOH) causes disabling symptoms that impair daily function and quality of life. The OHQ is a validated patient reported outcome with a symptom assessment (OHSA) and daily activity scale (OHDAS), widely used in clinical trials, despite the MCID being unestablished. Methods We analyzed data from two phase 3, randomized placebo-controlled trials (SEQUOIA and REDWOOD), evaluating ampreloxetine for symptomatic nOH in patients with Parkinson disease, multiple system atrophy, and pure autonomic failure. Using anchor-based and distribution-based methods, we calculated the MCID for the total OHQ score, OHSA and OHDAS composite subscales, and for the single dizziness/lightheadedness question (OHSA1). Results The analysis included 184 subjects from SEQUOIA and 128 from REDWOOD. The total OHQ MCID for improvement was a reduction of 0.9 to 1.2 points and for worsening was an increase of 0.7 to 1.1 points. The MCID for the OHSA composite ranged from a reduction of 0.9 to 1.3 points for improvement and an increase of 0.7 to 1.1 points for worsening. For the single item OHSA1, the MCID was a reduction of 2.0 to 3.0 points for improvement and an increase of 1.0 point for worsening. Due to poor correlation with the symptom-based anchors, a reliable MCID for the OHDAS component was not established. Conclusion These MCID thresholds for the OHQ, OHSA and OHSA item 1 alone, enhance the interpretability of scores and support their use in evaluating clinical benefit.