Abstract Details

Title Primary Outcome Measures for Early Phase ALS Trials - Are We Using the Best Measures?

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 076

Objective

Background BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects 1 in 40,000 Americans, with 5000 new diagnoses each year in the United States. The only approved therapy for this disease, Riluzole, has a modest effect, delaying disease progression on average by 3 months. Identifying new treatments for ALS is, therefore, crucial. Unfortunately, despite promising animal studies, most recent clinical trials in ALS have failed to meet their primary endpoint. While this may be due to lack of drug efficacy, it is also important to examine the outcome measures chosen in these trials, to prevent effective therapies from being discarded injudiciously. The utilization of highly responsive outcome measures, i.e. measures that are sensitive to meaningful changes in disease status over time, especially during the early phase testing of an intervention, may also be helpful in eliminating ineffective interventions earlier from the pipeline.

Design/Methods DESIGN/METHODS: We searched the Cochrane Central Register of Controlled Trials (CCTR) from 2001 to 2012 to identify all recent early phase (I-II) clinical drug trials. From trials thus selected, we determined the primary outcome measures used, and calculated concordance between expected rate of change in the outcome measures, to the rate of change seen in previously published natural history studies and trials.

Results RESULTS: Only a minority of the recent ALS trials actually had an expected rate of change concordant with predicted rate of change in outcome measure. Several trials used outcome measures other than ALSFRS, whose sensitivity remain unproven.

Conclusions CONCLUSIONS: Ascertaining drug efficacy in early phase clinical trials remains elusive due to the paucity of sensitive outcome measures, and the lack thereof of their proper use, likely due to study design constraints.

Authors/Disclosures
Amro Stino, MD (Michigan Medicine - University of Michigan) PRESENTER	Dr. Stino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for CSL Behring. Dr. Stino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Stino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Stino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Stino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexon. The institution of Dr. Stino has received research support from GBS-CIDP Foundation. The institution of Dr. Stino has received research support from Bristol Myers Squibb.
Sharique Ansari, MD (KaneHallBarry Neurology)	No disclosure on file
Sindhu Ramchandren, MD (Janssen Pharmaceutical Companies of Johnson & Johnson)	Dr. Ramchandren has received personal compensation for serving as an employee of Janssen Pharmaceutical Companies of Johnson & Johnson.
Leigh E. Charvet, PhD (NYU Langone)	Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare. Dr. Charvet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for YBrain. Dr. Charvet has stock in Johnson&Johnson.

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