title: Determining the minimum clinically important differences for outcomes in the DOMINO trial.
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.
authors.affiliation: King's College London, Institute of Psychiatry, Department of Old Age Psychiatry, London, UK. robert.j.howard@kcl.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
authors.forename: Patrick
authors.initials: P
authors.lastname: Phillips
authors.forename: Tony
authors.initials: T
authors.lastname: Johnson
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Bart
authors.initials: B
authors.lastname: Sheehan
authors.forename: James
authors.initials: J
authors.lastname: Lindesay
authors.forename: Peter
authors.initials: P
authors.lastname: Bentham
authors.forename: Alistair
authors.initials: A
authors.lastname: Burns
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.forename: Ian
authors.initials: I
authors.lastname: McKeith
authors.forename: Robert
authors.initials: R
authors.lastname: Barber
authors.forename: Tom
authors.initials: T
authors.lastname: Dening
authors.forename: Craig
authors.initials: C
authors.lastname: Ritchie
authors.forename: Rob
authors.initials: R
authors.lastname: Jones
authors.forename: Ashley
authors.initials: A
authors.lastname: Baldwin
authors.forename: Peter
authors.initials: P
authors.lastname: Passmore
authors.forename: David
authors.initials: D
authors.lastname: Findlay
authors.forename: Alan
authors.initials: A
authors.lastname: Hughes
authors.forename: Ajay
authors.initials: A
authors.lastname: Macharouthu
authors.forename: Sube
authors.initials: S
authors.lastname: Banerjee
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.forename: Martin
authors.initials: M
authors.lastname: Knapp
authors.forename: Richard G
authors.initials: RG
authors.lastname: Brown
authors.forename: Robin
authors.initials: R
authors.lastname: Jacoby
authors.forename: Jessica
authors.initials: J
authors.lastname: Adams
authors.forename: Mary
authors.initials: M
authors.lastname: Griffin
authors.forename: Richard
authors.initials: R
authors.lastname: Gray
mesh_terms: D000203:Activities of Daily Living; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D003657:Decision Making; D000077265:Donepezil; D015259:Dopamine Agents / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010880:Piperidines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic
chemical_list: D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D008559:Memantine