Expectations and clinical meaningfulness of randomized controlled trials

Alzheimers Dement. 2023 Jun;19(6):2730-2736. doi: 10.1002/alz.12959. Epub 2023 Feb 7.

Abstract

Alzheimer's disease (AD) clinical trials are designed and powered to detect the impact of a therapeutic intervention, and there has been considerable discussion on what constitutes a clinically meaningful change in those receiving treatment versus placebo. The pathology of AD is complex, beginning many years before clinical symptoms are detectable, with multiple potential opportunities for therapeutic engagement. Introducing treatment strategies early in the disease and assessing meaningful change over the course of an 18-month clinical trial are critical to understanding the value to an effective intervention. With new clinical trial data expected soon on emerging therapeutics from several AD studies, the Alzheimer's Association convened a work group of experts to discuss key considerations for interpreting data from cognitive and functional measures and what is considered a clinically meaningful benefit or meaningful slowing of this fatal disease. Our expectations of outcomes from therapeutic interventions in AD may need to be modified.

Keywords: Alzheimer disease; MCI; amyloid; clinical meaningfulness; clinical trial; cognition; cognitive impairment; dementia; mild cognitive impairment; tau.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / drug therapy
  • Cognitive Dysfunction* / diagnosis
  • Humans
  • Motivation
  • Randomized Controlled Trials as Topic