Impact of Independent Review on Potential MMSE Score Inflation at Screening in AD trials

Abstract

AbstractBackgroundThe Mini‐Mental State Examination (MMSE) is widely used as a screening tool in Alzheimer’s Disease (AD) clinical trials. Screening score inflation is documented in clinical trials of depression and anxiety. We investigated whether score distributions on several multi‐site multinational AD trials showed truncated scores around MMSE inclusion criteria cut‐off, and whether Independent Review (IRev), where site assessments are reviewed by independent clinicians, is an effective methodology to mitigate inclusion bias.MethodMMSE screening score distributions from several clinical trials of Early Symptomatic and Mild to Moderate AD were examined. To assess the impact of IRev on screening score distribution, we compared two studies with similar inclusion criteria (Early AD, MMSE ≥ 22; CDR GS = 0.5 or 1) one with no IRev and one with IRev via audio recording.ResultMMSE screening frequency distributions showed a statistically significant difference between IRev and No‐IREV groups (p < 0.001). The distributions for the two groups were also compared using several score ranges around the threshold. Significant group differences were observed across the score ranges; 20‐24 (D = 0.099, p = 0.01), 19‐25 (D = 0.094, p = 0.002), and 18‐26 (D = 0.0987, p < 0001), suggesting a smaller inclusion bias around the threshold in the IRev group.ConclusionWe observed that screening score inflation occurs in AD trials and Independent Review may be an effective strategy to reduce the number of subjects inappropriately enrolled in the study. IRev should be applied to assessments that fall around the required scored for study participation.