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P2‐054: The Structured Clinical Impression of Progressivity scale: Can we improve the success rate of Alzheimer's clinical trials by confirming progressivity?
Author(s) -
Babic Tomislav,
Veroff Amy E.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.364
Subject(s) - clinical trial , cognition , placebo , dementia , neuropsychology , clinical global impression , psychology , physical medicine and rehabilitation , medicine , psychiatry , disease , pathology , alternative medicine
Background: Lack of cognitive impairment progressivity is likely a key reason for confirmatory trial failure (trials > 6-months) where the placebo arm did not cognitively deteriorate at the study end (phenserine, tramiprosate, MEM103). Three important abuses of NINCDS-ADRDA criteria have been observed during the source data verification process: absence of neuropsychological tests which confirm dementia, absence of neuroimaging to rule out other possible causes, lack of progressivity of cognitive impairment prior to baseline. Such pseudo-placebo effect has been observed in rosiglitazone clinical trials, where 40% of patients did not have evidence of a progressive course prior to baseline. Additional effort should be made to rule out patients with MCI or dementia with argyrophylic grains where cognitive deterioration is very slow and the difference will be difficult to capture in short trials (6-12 months duration). Described here is a potential screening tool that could confirm progressivity for subject inclusion in clinical trials. Methods: 1) Literature search for studies requiring evidence of progression as an inclusion criterion. 2) Design of the Structured Clinical Impression of Progressivity (SCIP) scale that captures evidence of progressivity with a weighted scoring scheme for each domain and total cut-off score. There are three domains: Diagnosis (how many years ago the AD diagnosis was made), Longitudinal Data (cognitive, functional, global scales), Caregiver (global impression of 6-month change in cognitive and functional activities). Results: There appears to be only one confirmatory protocol that specifically requested evidence of cognitive deterioration prior to baseline as an inclusion criterion. This protocol successfully avoided pseudo-placebo effect in both primary (ADAS-Cog) and secondary (DAD) outcome measures after 6 months of drug exposure. Conclusions: We are convinced that lack of progressivity of cognitive impairment is a critical factor in failed AD clinical trials and we describe the development of a screening tool that would enable sites to exclude subjects who don’t have confirmation of progressivity.