EVALUATION OF SELECTION CRITERIA USED IN ALZHEIMERS-DISEASE CLINICAL-TRIALS

Background: In the absence of a biological marker for Alzheimer's dise ase (AD), diagnosis has to be achieved using clinical criteria sets su ch as those outlined in DSM-IV, NINCDS-ADRDA, or ICD-10. As these crit eria are quite broadly defined, there may be inter-rater variability i n interpretation. Methods: Using a previously published CT scan measur ing technique which correlates well with diagnoses achieved using the NINCDS-ADRDA criteria as interpreted at our clinic, we chose to indepe ndently examine and reach a diagnosis in patients selected for partici pation in clinical trials of therapeutic agents for the treatment of A D. Forty-four CT scans from six investigators across Canada were exami ned using this model. All patients had been dia NINCDS-ADRDA criteria and were deemed acceptable to participate in a clinical trial. Results : The diagnostic concordance achieved in the original published model was 91.5%. The diagnostic concordance in the population currently bein g studied was 77.3%. However when examined by site, results ranged fro m 57.1% to 100%. Using the model, an index of atrophy and a probabilit y of diagnosis of AD can be determined. Across sites, there were stati stically significant differences in these measures (p less than or equ al to 0.035). The mean probability of diagnosis of AD across sites ran ged from 0.56 to 0.94. Although the sites with lower probabilities had slightly lower mean ages and slightly less atrophy, there was no over all correlation of the atrophy measures with age. Conclusions: Current results raise the possibility that the selection of patients for AD c linical trials using current diagnostic criteria sets may not be adequ ate and conclusions with respect to agent efficacy could be flawed.