PMID- 19187414
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20220409
IS  - 1532-5415 (Electronic)
IS  - 0002-8614 (Linking)
VI  - 57
IP  - 3
DP  - 2009 Mar
TI  - Systematic review of measures of clinical significance employed in randomized 
      controlled trials of drugs for dementia.
PG  - 536-46
LID - 10.1111/j.1532-5415.2008.02122.x [doi]
AB  - The ability to define thresholds for the clinical significance (clinical 
      importance) of outcome measures in dementia drug research is critical to 
      determining the changes on outcome measures that patients and families would 
      consider worth the cost and worth risking the side effects of medications (i.e., 
      clinical importance is central to informed consent when starting such 
      medications). Thresholds for clinical significance are also required for drug 
      trial sample size calculation (if the studies are to be powered to detect 
      clinically important difference) and for decisions regarding whether medications 
      should be accepted on formularies and should be funded. To better understand what 
      measures of clinical significance have been employed in dementia drug research, a 
      systematic review was performed of double-blind randomized controlled trials 
      (RCTs) of cholinesterase inhibitors and memantine in subjects with Alzheimer's 
      disease, vascular dementia, mixed dementia, and mild cognitive impairment. Of the 
      57 dementia drug RCTs reviewed, only 46% discussed the clinical significance of 
      their results. The most commonly cited measures of clinical significance were a 
      4-point change in the Alzheimer's Disease Assessment Scale--Cognitive Subscale 
      and changes on global scales. The majority of measures of clinical significance 
      were opinion based. Only one study empirically measured patient perspective 
      regarding thresholds for clinical significance. Despite being central to the 
      interpretation of trial results and to decisions regarding whether to employ 
      trial findings in clinical practice, patient- and caregiver-centered measures of 
      clinical significance have not been adequately studied and integrated into 
      dementia drug RCTs. It is recommended that discussions of clinical importance 
      receive greater emphasis in research standards published by organizations such as 
      the CONSORT group (http://www.consort-statement.org). Drug formulary review 
      committees and licensing agencies (e.g., U.S. Food and Drug Administration, 
      European Agency for the Evaluation of Medicinal Products, Health Canada) should 
      consider requiring an assessment of clinical significance of the drugs they 
      review. To move this field forward, funding agencies should consider initiating 
      requests for proposals focused on the determination of the minimally clinically 
      important difference (MCID) of outcome measures employed in dementia research. 
      Once empirical data on MCIDs are available, then these funding agencies should 
      consider supporting a consensus conference to review and select the optimal 
      measures of clinical importance in dementia research. A preliminary 
      organizational framework of measures of clinical significance is presented in 
      this article to facilitate the work of such a consensus forum.
FAU - Molnar, Frank J
AU  - Molnar FJ
AD  - Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
FAU - Man-Son-Hing, Malcolm
AU  - Man-Son-Hing M
FAU - Fergusson, Dean
AU  - Fergusson D
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20090129
PL  - United States
TA  - J Am Geriatr Soc
JT  - Journal of the American Geriatrics Society
JID - 7503062
RN  - 0 (Nootropic Agents)
SB  - IM
CIN - J Am Geriatr Soc. 2009 Oct;57(10):1947; author reply 1947-8. PMID: 19807804
MH  - Aged
MH  - Alzheimer Disease/diagnosis/*drug therapy
MH  - Data Interpretation, Statistical
MH  - Double-Blind Method
MH  - Humans
MH  - Nootropic Agents/*therapeutic use
MH  - Randomized Controlled Trials as Topic/*statistics & numerical data
MH  - Treatment Outcome
RF  - 50
EDAT- 2009/02/04 09:00
MHDA- 2009/03/31 09:00
CRDT- 2009/02/04 09:00
PHST- 2009/02/04 09:00 [entrez]
PHST- 2009/02/04 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
AID - JGS2122 [pii]
AID - 10.1111/j.1532-5415.2008.02122.x [doi]
PST - ppublish
SO  - J Am Geriatr Soc. 2009 Mar;57(3):536-46. doi: 10.1111/j.1532-5415.2008.02122.x. 
      Epub 2009 Jan 29.