PMID- 10559571
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20220409
IS  - 1420-8008 (Print)
IS  - 1420-8008 (Linking)
VI  - 10
IP  - 6
DP  - 1999 Nov-Dec
TI  - Key methodological features of randomized controlled trials of Alzheimer's 
      disease therapy. Minimal clinically important difference, sample size and trial 
      duration.
PG  - 534-40
AB  - BACKGROUND: The results of clinical trials are routinely presented in terms of 
      statistical significance, which may or may not indicate clinical significance. 
      Analysis of the minimal clinically important difference (MCID) of cognitive 
      scales has received little attention to date. OBJECTIVES: By reviewing the key 
      methodological features (sample size, duration, statistical and clinical 
      significance) of clinical trials examining the efficacy of tacrine in the 
      treatment of Alzheimer's disease (AD), we assessed their ability to detect 
      clinically important changes in cognition. DESIGN: The value for the MCID of the 
      Mini-Mental State Examination (MMSE) was determined by surveying specialists in 
      neurology and geriatric medicine. This value was then used to interpret the 
      clinical significance of the results of published randomized controlled trials 
      (RCTs) assessing the efficacy of tacrine in the treatment of AD and to 
      retrospectively determine their optimal sample size and trial duration. RESULTS: 
      The mean survey MCID for the MMSE was 3.72 (95% confidence interval 3.50-3.95) 
      points. Only 2 of 12 tacrine RCTs using the MMSE found a statistically 
      significant difference in MMSE scores for patients taking tacrine compared with 
      those taking placebo. These improvements were not clinically significant when 
      compared with the survey MMSE MCID. For parallel trials of tacrine in AD, the 
      smallest sample size and minimum trial duration required to demonstrate a 
      clinically significant difference were calculated to be 53 subjects and 1 year, 
      respectively. Five of the 7 parallel trials met the required sample size; 
      however, none of them met the criteria for trial duration. CONCLUSIONS: When 
      using the MMSE as an outcome measure, no tacrine trial reported results that were 
      clinically significant as perceived by clinicians working with dementia patients. 
      Application of a range of plausible MCIDs to the parallel design RCTs also 
      demonstrated that 2 of 7 of these trials did not have sufficient sample size, and 
      none had sufficient duration of treatment to reliably detect clinically 
      meaningful changes in cognition. Future clinical trials in this area will need to 
      incorporate the evolving knowledge of MCIDs in order to increase their chance of 
      detecting clinically relevant results. CopyrightCopyright 1999S.KargerAG,Basel
FAU - Burback, D
AU  - Burback D
AD  - Geriatric Assessment Unit, Ottawa Hospital, Civic Campus, Ottawa, Ontario, 
      Canada.
FAU - Molnar, F J
AU  - Molnar FJ
FAU - St John, P
AU  - St John P
FAU - Man-Son-Hing, M
AU  - Man-Son-Hing M
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Dement Geriatr Cogn Disord
JT  - Dementia and geriatric cognitive disorders
JID - 9705200
RN  - 0 (Nootropic Agents)
RN  - 4VX7YNB537 (Tacrine)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*drug therapy/*psychology
MH  - Cognition/drug effects/physiology
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Humans
MH  - Nootropic Agents/*therapeutic use
MH  - Psychiatric Status Rating Scales
MH  - Randomized Controlled Trials as Topic/*methods
MH  - *Research Design
MH  - Sample Size
MH  - Tacrine/therapeutic use
MH  - Time Factors
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 17201 [pii]
AID - 10.1159/000017201 [doi]
PST - ppublish
SO  - Dement Geriatr Cogn Disord. 1999 Nov-Dec;10(6):534-40. doi: 10.1159/000017201.