Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil.
BACKGROUND
No guidelines exist to help physicians determine whether functional and health-related quality of life (HRQoL) changes observed following treatment of patients with pulmonary arterial hypertension (PAH) represent important benefits. These analyses were undertaken to help define a minimally important difference (MID) in exercise capacity, measured by the 6-min walk distance (6MWD), and HRQoL, measured by the Short Form-36 (SF-36) questionnaire in patients with PAH.


METHODS
Data from a 12-week sildenafil study in patients with PAH were used to calculate MIDs for 6MWD and the SF-36 physical functioning, role-physical, social functioning, and vitality scales using effect size, SEM, and SE of the difference approaches. Data from all patients enrolled into the treatment groups in the study were included.


RESULTS
A range of plausible MID estimates, including a score change for SF-36 scales and a change in distance walked in meters for 6MWD, were generated for each end point. Mean values were calculated for each outcome and recommended as MIDs for each parameter. Based on these computations, the mean MIDs for the SF-36 physical functioning, role-physical, social functioning, and vitality scales and for 6MWD were 13, 25, 21, and 15 points, and 41 m, respectively.


CONCLUSIONS
This is the first clinical investigation to estimate MIDs for key SF-36 domains and 6MWD in patients with PAH and provides a much needed metric for interpreting the level of change in patients with PAH against which other treatments and trials can be measured.
Gilbert
Claire
C
PGRD, Pfizer Ltd., Sandwich, Kent, UK. Electronic address: claire.gilbert@pfizer.com.
Brown
Martin C J
MCJ
Global Health Outcomes Research, UCB Celltech, Slough, Berkshire, UK.
Cappelleri
Joseph C
JC
Pfizer Inc, Groton, CT.
Carlsson
Martin
M
Pfizer Inc, Groton, CT.
McKenna
Stephen P
SP
Galen Research, University of Central Lancashire, Manchester, UK.
D004311:Double-Blind Method; D017079:Exercise Tolerance; D005260:Female; D006304:Health Status; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D017063:Outcome Assessment, Health Care; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011788:Quality of Life; D015203:Reproducibility of Results; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate