ADAS-Cog central monitoring and intervention with raters: A critical extension and integral component of Alzheimer trials rater training programs

Though early ADAS-Cog publications demonstrate validity, reliability, and sensitivity to change, maintaining those psychometric qualities is difficult in multi-center clinical trials. The ADAS-Cog is ubiquitously used, and until there are better measures the challenge is to find effective methods to reduce rater variance while maintaining ADAS-Cog data quality. Rater pre-qualification, training, and certification are well established components of comprehensive rater training programs. Central expert review of study subject ratings during a clinical trial reveals errors that can be addressed with additional training as they are detected to prevent further errors. Safety and subject selection issues can also be identified in a timely way. Raters in 2 ongoing Alzheimer's clinical trials (NCT00810147 & NCT00890890) were pre-qualified based on education and experience, trained and certified on the ADAS-Cog. Score sheets for the cognitive scales were faxed in for expert central review as completed, queries documented and additional training was provided to problematic raters. Total queries for all scales in Study 1: 1249 (663 scoring); 1 inclusion criteria violation; Study 2 (started 4 months later): 380 queries (164 scoring); 4 inclusion criteria violations. In a sample of 260 ADAS-Cog queries, 68% were scoring errors; Word Recognition, Orientation, and Constructional Praxis contributed 71% of the total ADAS-Cog queries. As centrally monitored raters received feedback/re-training, the mean number of cognitive scale queries per subject visit decreased 32% (from 3.1 per subject visit to 2.1) over 6 months in Study 1. Expert central monitoring of study subject ADAS-Cog data reveals errors and can reduce noise and risk in AD clinical trials in a number of ways. By centrally monitoring ratings during the study, raters making errors may be remediated, reducing the average number of errors per visit going forward. Central monitoring also identifies other issues such as safety issues when abrupt decreases in cognitive function are observed and identifies inclusion criteria violations.