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P4‐177: BASELINE COGNITIVE SEVERITY DOES NOT PREDICT RATE OF CHANGE IN THE ADAS‐COG CLINICAL TRIALS
Author(s) -
Schneider Lon S.,
Kennedy Richard E.,
Wang Guoqiao,
Cutter Gary
Publication year - 2014
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.2014.05.1694
Subject(s) - post hoc analysis , post hoc , medicine , cognition , baseline (sea) , clinical trial , cognitive decline , cog , dementia , disease , psychiatry , oceanography , artificial intelligence , computer science , geology
what type of patients enroll in these studies and whether participant characteristics vary by region. Methods: We examined data from four multinational Phase III clinical trials conducted in patients with mild-to-moderate AD and sponsored by Eli Lilly and Company.We assigned the 31 participating nations to seven geographic regions: North America (NA), South America/Mexico (SA), Western Europe (WE), Eastern Europe/Russia (EE), Australia/South Africa (AU), Asia (AS), and Japan (JP). We assessed regional differences in participant demographics and baseline scores on clinical outcome measures including the Mini-Mental State Examination (MMSE), the AD Assessment Scale-cognitive subscale (ADAS-cog11); Clinical Dementia Rating Scale Sum of Boxes (CDR-SB); AD Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). If an overall effect of region was observed using Analysis of Variance or Chi-square tests, pairwise comparisons adjusted for multiple comparisons were performed. Results:NA,WE, andAUwere similar in the proportions ofmale participants, apolipoprotein ε4 carriers, and participants enrolling with a spouse study partner; AS, EE, and SA had lower proportions for these variables. NA and SA had older, while AS and SA had lower educated, participants than the remaining regions. Most (86%) participants took an approved AD therapy at baseline; anti-AD drug use was highest in NA, WE, and JP. Dual therapy was most frequent in NA. Regions differed on all baseline clinical measures. NA, WE, JP, and AU had milder scores and AS, SA, and EE had more moderate severity for the MMSE. EE had worse ADAS-cog11 scores than all other regions. EE and SA had more severe scores for the ADCS-ADL and the CDR-SB. Mean scores in AS were milder than all regions except JP for the CDR-SB. NPI scores in AS and JP were lower than all other regions. Conclusions: These findings suggest that trial populations may differ across geographic regions. Multinational enrollment may introduce heterogeneity. Our data provide some guidance as to the variables that contribute to the heterogeneity.