Determining the minimum clinically important differences for outcomes in the DOMINO trial.
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.
Howard
Robert
R
King's College London, Institute of Psychiatry, Department of Old Age Psychiatry, London, UK. robert.j.howard@kcl.ac.uk
Phillips
Patrick
P
Johnson
Tony
T
O'Brien
John
J
Sheehan
Bart
B
Lindesay
James
J
Bentham
Peter
P
Burns
Alistair
A
Ballard
Clive
C
Holmes
Clive
C
McKeith
Ian
I
Barber
Robert
R
Dening
Tom
T
Ritchie
Craig
C
Jones
Rob
R
Baldwin
Ashley
A
Passmore
Peter
P
Findlay
David
D
Hughes
Alan
A
Macharouthu
Ajay
A
Banerjee
Sube
S
Jones
Roy
R
Knapp
Martin
M
Brown
Richard G
RG
Jacoby
Robin
R
Adams
Jessica
J
Griffin
Mary
M
Gray
Richard
R
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
D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D008559:Memantine