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P1‐440: Pharmacokinetics of ponezumab (PF‐04360365) following a single‐dose intravenous infusion in Japanese patients with mild‐to‐moderate Alzheimer's disease: Preliminary results
Author(s) -
Zhao Qinying,
Abe Sadahiro,
Miyoshi Izuru,
Bednar Martin M.,
Kupiec James W.,
Fujimoto Yoko
Publication year - 2010
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.2010.05.995
Subject(s) - pharmacokinetics , cmax , dosing , medicine , placebo , volume of distribution , pharmacology , area under the curve , urology , gastroenterology , pathology , alternative medicine
Background: The Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-Cog) is the most commonly used primary efficacy measure in Alzheimer’s disease clinical trials. In general, the (11 item) ADASCog has demonstrated sensitivity to change across a range of dementia severities. However, some clinical research studies now include some additional items (e.g. delayed word recall, maze test and digit cancellation) hoping to better assess the early stages of dementia as well as executive functioning. Earlier research has demonstrated considerable variability in how raters have been trained to administer and score the (11 item) ADAS-Cog in clinical trials. Additionally, with increased globalization of studies, the potential for considerable differences in rater experience exists. Initial qualification rates for raters attempting to participate in studies utilizing the 11 item ADAS-Cog were compared to studies utilizing some or all of the additional items. Methods: A proprietary database identified all raters who were trained on and who attempted to qualify to administer and score the ADAS-Cog in 32 clinical trials. Raters were stratified into 2 groups those tested on the original 11 item ADAS-Cog and those tested on scale versions that incorporated additional item(s). Testing consisted of watching and scoring a video of the scale being administered to a patient. Initial qualification rates (scoring to a predefined criteria) were compared. Results: In 26 studies employing the 11 item ADAS-Cog, 4223 of 4587 raters (92.1%) qualified to rate on their initial attempt. Additionally, 1313 raters out of 1595 (82.3%) potential raters in the 6 studies utilizing additional item(s) were successful on their initial attempts to qualify to rate. A chi-square analysis determined that this difference in initial qualification rates is significant (<0.0001). Conclusions: The incorporation of additional item(s) into the original 11 item ADAS-Cog appears to provide an added challenge to raters who attempt to qualify to rate in those studies. Possible explanations include training variability; lack of familiarity with these items, their administration and scoring, and what they aim to assess. Given the difference in initial qualification rates when additional item(s) are used, surveillance and analysis of raters’ performance on these items throughout a trial is warranted.