Ryan Walter, United States of America
PRA Health Science Health ScienceAuthor Of 1 Presentation
ADJUDICATING MILD COGNITIVE IMPAIRMENT DUE TO ALZHEIMER’S DISEASE AS A NOVEL ENDPOINT EVENT IN THE TOMORROW STUDY
Abstract
Aims
MCI onset is an essential outcomes event in Alzheimer prevention trials and a compelling milestone for clinically meaningful change. Determining MCI, however, may be variable and subject to disagreement. Adjudication procedures may improve the reliability of these determinations. We report the performance of an adjudication committee for an international AD prevention trial.
Methods
The TOMMORROW study (NCT01931566) selected cognitively normal participants at increased genetic risk for Alzheimer’s and randomized them to low-dose pioglitazone or placebo treatment. When adjudication criteria were triggered a participant’s clinical information was randomly assigned to a 3-member panel of an independent adjudication committee. Determination of whether a participant reached MCI or AD proceeded through up to three review stages, requiring unanimous decision.
Results
Of 3494 participants randomized, 648 cases involving 386 participants were adjudicated, resulting in 92 MCI events and 4 AD dementia. A total of 235 (61%) participants required only one adjudication. Most cases, 485 (74.8%), were decided by blinded independent review (Stage 1); 14.0% required broader collaborative review (Stage 2); and 11.1% full committee discussion (Stage 3). Concordance between site investigators’ clinical diagnoses and the adjudication committee’s endpoint decisions increased from 50% to approximately 93% after around 100 cases and was maintained at that level.
Conclusions
These outcomes demonstrated the extent of uncertainty among trial investigators and agreement between adjudicators when the transition to MCI due to AD was prospectively assessed. Reliable, accurate assessment of clinical events is critical for prevention trials and may mean the difference between a trial’s success and failure.