What is the clinical evidence from this study?

Study design: Other. Population: Neurogenic orthostatic hypotension (n=312). Intervention: Ampreloxetine vs. Placebo. Primary outcome: Minimally clinically important difference (MCID) for the total OHQ score.

October 24, 2025Clinical Autonomic Research4 citationsOpen Access

Establishing minimally clinically important differences for the orthostatic hypotension questionnaire (OHQ)

HKHoracio KaufmannDysautonomia Foundation JPJose‐Alberto PalmaTufts University RVRoss G. VickeryDS Biopharma (Ireland)

Key Result

The minimally clinically important difference for the Orthostatic Hypotension Questionnaire composite score was established as a reduction of 0.9 to 1.2 points for improvement and an increase of 0.7 to 1.1 points for worsening.

Structured PICO

Population

312 patients (mean age 68 years, 30.8% female) with symptomatic neurogenic orthostatic hypotension associated with Parkinson disease, multiple system atrophy, or pure autonomic failure, analyzed to establish the minimally clinically important difference for the Orthostatic Hypotension Questionnaire.

Intervention

Ampreloxetine 10 mg oral once daily (in the underlying trials)

Comparator

Matching placebo (in the underlying trials)

Outcome

Minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ) total score, OHSA composite subscale, and single dizziness/lightheadedness question (OHSA1)patient reported

Establishing the minimally clinically important difference for the Orthostatic Hypotension Questionnaire enhances the interpretability of patient-reported outcomes in clinical trials for neurogenic orthostatic hypotension.

Limitations

Analyses were based on data from clinical trials investigating a single agent, ampreloxetine.
Anchor instruments (PGI-C and PGI-S) are inherently subjective and rely on recall.
Enrollment criteria restricted patients with seated plasma norepinephrine levels <100 pg/ml and required a minimum symptom severity score, limiting generalizability.
Mismatch between symptom-based anchors and the activity focus of the OHDAS led to inconsistent findings.

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 0.9-1.2 points and for worsening was an increase of 0.7-1.1 points. The MCID for the OHSA composite ranged from a reduction of 0.9-1.3 points for improvement and an increase of 0.7-1.1 points for worsening. For the single-item OHSA1, the MCID was a reduction of 2.0-3.0 points for improvement and an increase of 1.0 point for worsening. Owing to poor correlation with the symptom-based anchors, a reliable MCID for the OHDAS component was not established. CONCLUSIONS: 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.

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