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Change in 6MWD as a Predictor of Survival of PAH: Minimal Clinically Important Difference (MID) and Beyond

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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Minai

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Rationale: Estimates of the 6MWD MID have been previously reported using anchor-based and distributional method. We used the ARIES database to estimate the placebo-corrected MID for PAH as well as to investigate the change in 6MWD in the months leading up to a fatal event. 

Methods: Data from the combined ARIES 1 & 2 placebo controlled studies (ARIES-C) as well as the extension study (ARIES-E) were used. Both anchor based (SF-36) and distributional methods were used to estimate the 6MWD MID. The physical functioning component (PFC) score of the SF-36 was used as it had the highest correlation with the change in 6MWD (r=0.32); MID anchoring to the physical component summary (PCS) score was also calculated. A 5 point change in the SF-36 components was defined as the MID. Linear regression of change in PFC/PCS against change in 6MWD was used to calculate the MID. The 6MWD MID was calculated for the total population as well as for IPAH and CTD subgroups. Survival probability was calculated using the MID achieved at month 3 and 6 post treatment initiation. Additionally, the most recent 6 month change in 6MWD prior to death was compared to that of survivors. 

Results: This was a treatment naïve population; therefore placebo corrected MID's are also presented. Using anchor based methodology a 39m MID for 6MWD was observed. The distributional method gave similar results (34 – 40m). The placebo corrected MID was 26m using the PFC score. The anchor-based 6MWD MID for the IPAH population was greater (43m) than that for the CTD population (25m). The placebo corrected 6MWD MID of > 26m or < 26m at 6 months post treatment initiation was predictive of survival (Fig 1) whereas a similar change at 3 months post treatment initiation was not. There was a mean reduction of 40m (Alive: -8.7m versus Dead: -49.1m) for the last available 6 month change in 6MWD prior to death. 

Conclusions: We report that a placebo-corrected 6MWD MID (26m) at 6 months post treatment initiation was predictive of survival in our PAH cohort. We also report that a significant reduction in 6MWD (-40m) over 6 months may portend a poor outcome. The uncorrected MID's are similar to previous reports (33 – 41m). These findings may be very meaningful in the conduct of future clinical trials.