PMID- 34087114
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20211027
IS  - 2215-0374 (Electronic)
IS  - 2215-0366 (Linking)
VI  - 8
IP  - 11
DP  - 2021 Nov
TI  - The need to show minimum clinically important differences in Alzheimer's disease 
      trials.
PG  - 1013-1016
LID - S2215-0366(21)00197-8 [pii]
LID - 10.1016/S2215-0366(21)00197-8 [doi]
AB  - Deciding on the smallest change in an outcome that constitutes a clinically 
      meaningful treatment effect (ie, the minimum clinically important difference 
      [MCID]) is fundamental to interpreting clinical trial outcomes, making clinical 
      decisions, and designing studies with sufficient statistical power to detect any 
      such effect. There is no consensus on MCIDs for outcomes in Alzheimer's disease 
      trials, but the US Food and Drug Administration's consideration of aducanumab 
      clinical trials data has exposed the uncertainty of the clinical meaning of 
      statistically significant but small improvements. Although MCIDs for outcomes, 
      including Clinical Dementia Rating-Sum of Boxes and Mini-Mental State Examination 
      in Alzheimer's disease have been reported, the Food and Drug Administration's 
      guidelines, drafted in 1989 to facilitate regulatory approval of substantially 
      effective antidementia drugs, do not specify quantified minimum differences. 
      Although it is important that regulatory requirements encourage drug development 
      and approval, without MCIDs, sponsors are motivated to power trials to detect 
      statistical significance for only small and potentially inconsequential effects 
      on clinical outcomes. MCIDs benefit patients, family members, caregivers, and 
      health-care systems and should be incorporated into clinical trials and drug 
      development guidance for Alzheimer's disease.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Liu, Kathy Y
AU  - Liu KY
AD  - Division of Psychiatry, University College London, London, UK. Electronic 
      address: kathy.liu@ucl.ac.uk.
FAU - Schneider, Lon S
AU  - Schneider LS
AD  - Department of Psychiatry and the Behavioral Sciences, and Department of 
      Neurology, Keck School of Medicine, and Leonard Davis School of Gerontology of 
      the University of Southern California, Los Angeles, CA, USA.
FAU - Howard, Robert
AU  - Howard R
AD  - Division of Psychiatry, University College London, London, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210601
PL  - England
TA  - Lancet Psychiatry
JT  - The lancet. Psychiatry
JID - 101638123
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 105J35OE21 (aducanumab)
SB  - IM
MH  - Alzheimer Disease/diagnosis/*drug therapy
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Caregivers/*statistics & numerical data
MH  - Clinical Decision-Making/*ethics
MH  - Clinical Trials as Topic
MH  - Delivery of Health Care/*statistics & numerical data
MH  - Drug Development/*standards/statistics & numerical data
MH  - Family/psychology
MH  - Guidelines as Topic
MH  - Humans
MH  - Mental Status and Dementia Tests/statistics & numerical data
MH  - Minimal Clinically Important Difference
MH  - Outcome Assessment, Health Care
MH  - United States
MH  - United States Food and Drug Administration/organization & administration
COIS- Declaration of interests Outside of this Personal View, LSS reports grants and 
      personal fees from Eli Lilly, Merck, and Roche/Genentech; personal fees from 
      Boehringer Ingelheim, Neurim, Ltd, Neuronix, Ltd, Cognition, Eisai, Takeda, vTv, 
      IBC, Abbot, and Samus; and grants from Biogen, Novartis, Biohaven, and Washington 
      Univ/ NIA DIAN-TU. RH and KYL declare no competing interests.
EDAT- 2021/06/05 06:00
MHDA- 2021/10/28 06:00
CRDT- 2021/06/04 20:10
PHST- 2021/03/26 00:00 [received]
PHST- 2021/04/19 00:00 [revised]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/06/05 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/06/04 20:10 [entrez]
AID - S2215-0366(21)00197-8 [pii]
AID - 10.1016/S2215-0366(21)00197-8 [doi]
PST - ppublish
SO  - Lancet Psychiatry. 2021 Nov;8(11):1013-1016. doi: 10.1016/S2215-0366(21)00197-8. 
      Epub 2021 Jun 1.