There are currently no guidelines or standards to help physicians determine whether or not the treatment provided to patients with pulmonary arterial hypertension (PAH) results in a clinically important benefit. This study was undertaken to define the level of change in exercise capacity, as measured by the 6-minute walk distance (6MWD), and functioning and well-being, as measured by the SF-36, that is clinically meaningful in patients with PAH: a minimally important difference (MID).
Data from a 12-week sildenafil study were used to evaluate an MID for 6MWD and the physical functioning, role-physical, social functioning, and vitality domains of the SF-36 in patients with PAH, using the following distribution-based approaches: Effect Size (ES), Standard Error of Measurement (SEM), and Standard Error of the Difference (Sdiff). The total population enrolled in the study, including the placebo- and the sildenafil-treated groups, was used for these analyses.
An MID was established for each of the end points based on the average of the distribution-based estimates (Table). These estimates are a point change in score for the SF-36 and a change in distance walked in meters for the 6MWD.
A wide range of estimates were obtained for each end point using three distribution-based methods to explore a minimally important change. The average of these was then taken as an MID value for each end point. This is the first clinical investigation to establish an MID for key SF-36 domains and 6MWD in patients with PAH. Further work incorporating the patient and clinical perspective of change using anchor-based methods would complement and supplement the findings reported here.
The analyses and results presented here may be useful in establishing clinical guidelines to determine the effectiveness of PAH therapies objectively.
Minimally Important Differences for Pre-specified SF-36 Domains and 6MWDOutcomeMIDRange of estimatesSF-36 physical functioning113.8-20.9SF-36 role physical218-40.5SF-36 social functioning165.2-33.1SF-36 vitality134.3-256MWD (m)3912.7-77.9
Claire Gilbert, Shareholder Pfizer Ltd; Employee Pfizer Ltd.