Abstract Details

Title Capture of Functional Decline in International Phase III Multi-Centre Clinical Trial Data Using the King's Amyotrophic Lateral Sclerosis (ALS) Staging System

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 074

Objective

Background BACKGROUND: Phase III ALS trials measure functional end points such as the revised Functional Rating Scale (ALS-FRSr). Patients progress at variable rates, with some dying during the course of the trial, but since these are usually the patients with worse functional scores, only the surviving cohort contributes to the data and it is difficult to show an effect of treatment on function. We proposed a staging system consisting of four clinical milestones reached at standardized proportions of the disease course.

Design/Methods DESIGN/METHODS: Median and interquartile range of ALS-FRSr were calculated for each trial visit to determine change over absolute time course. ALS-FRSr was used to calculate which clinical milestone of the staging system patients reached at every visit. Median and interquartile range of ALS-FRSr were calculated for each Stage, reflecting change over standardized time. ALS-FRSr decline was compared over absolute versus standardized time.

Results RESULTS: There were 512 patients. Median ALS-FRSr scores at each visit were Month(M): M0 39, M1 39, M2 38, M3 37, M6 34, M9 32.5, M12 30, M15 29, M18 27.5. ALS-FRSr scores declined with each Stage(S): S1 43, S2 39, S3 34, S4A 28, S4B 23. Medians were not significantly different between every month of the trial. However medians were significantly different (p<0.0001) between stages.

Conclusions CONCLUSIONS: Over the course of the trial median scores declined by only 11.5 points, whereas measured using the standardized times of the staging system, scores declined by 20 points. Patients surviving until month 18 are enriched for those with slower progression and will have higher scores. Using standardized times should improve power to detect differences between treatment arms.

Authors/Disclosures
PRESENTER	No disclosure on file
Ashley Jones	No disclosure on file
Martin R. Turner, MBBS, PhD, MA, FRCP (University of Oxford)	No disclosure on file
Nigel P. Leigh	No disclosure on file
	No disclosure on file
Vincent Meininger, MD, PhD (Hopital Des Peupliers)	No disclosure on file
Krzysztof W. Selmaj (University of Warmia and Mazury)	Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.

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