Determining the minimum clinically important differences for outcomes in the DOMINO trial

Int J Geriatr Psychiatry. 2011 Aug;26(8):812-7. doi: 10.1002/gps.2607. Epub 2010 Sep 16.

Abstract

Background: Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.

Methods: As part of the development of the Statistical Analysis Plan for the DOMINO trial, investigators met to consider expert opinion- and distribution-based values for the MCID and triangulated these to provide appropriate values for three outcome measures, the Standardised Mini-mental State Examination (sMMSE), Bristol Activities of Daily Living Scale (BADLS) and Neuropsychiatric Inventory (NPI). Only standard deviations (SD) were presented to investigators who remained blind to treatment allocation.

Results: Adoption of values for MCIDs based upon 0.4 of the SD of the change in score from baseline on the sMMSE, BADLS and NPI in the first 127 participants to complete DOMINO yielded MCIDs of 1.4 points for sMMSE, 3.5 for BADLS and 8.0 for NPI.

Conclusions: Reference to MCIDs is important for the full interpretation of the results of dementia trials and those conducting such trials should be open about the way in which they have determined and chosen their values for the MCIDs.

MeSH terms

  • Activities of Daily Living
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Cholinesterase Inhibitors / therapeutic use*
  • Data Interpretation, Statistical*
  • Decision Making
  • Donepezil
  • Dopamine Agents / therapeutic use*
  • Humans
  • Indans / therapeutic use
  • Memantine / therapeutic use
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Piperidines / therapeutic use
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic*

Substances

  • Cholinesterase Inhibitors
  • Dopamine Agents
  • Indans
  • Piperidines
  • Donepezil
  • Memantine