Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials

J Scott Andrews; Urvi Desai; Noam Y Kirson; Miriam L Zichlin; Daniel E Ball; Brandy R Matthews

doi:10.1016/j.trci.2019.06.005

Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials

Alzheimers Dement (N Y). 2019 Aug 2:5:354-363. doi: 10.1016/j.trci.2019.06.005. eCollection 2019.

Authors

J Scott Andrews¹, Urvi Desai², Noam Y Kirson², Miriam L Zichlin², Daniel E Ball¹, Brandy R Matthews¹

Affiliations

¹ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
² Analysis Group, Inc., Boston, MA, USA.

Abstract

Introduction: This study estimated the minimal clinically important difference (MCID) for Mini Mental State Examination, Clinical Dementia Rating Scale sum of boxes, and Functional Activities Questionnaire across the Alzheimer's disease (AD) spectrum.

Methods: Retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016) and MCID for clinical outcomes were estimated using anchor-based (clinician's assessment of meaningful decline) and distribution-based (1/2 baseline standard deviation) approaches, stratified by severity of cognitive impairment.

Results: On average, a 1-3 point decrease in Mini Mental State Examination, 1-2 point increase in Clinical Dementia Scale sum of boxes, and 3-5 point increase in Functional Activities Questionnaire were indicative of a meaningful decline. The MCID values generally increased by disease severity; the effect size and standardized response mean for those with meaningful decline were consistently in the acceptable ranges for MCID.

Discussion: These findings can inform design and interpretation of future clinical trials.

Keywords: Alzheimer's disease; CDR; FAQ; MCID; MMSE; Meaningful decline.

Abstract

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