PMID- 24613705
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20150119
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Linking)
VI  - 11
IP  - 1
DP  - 2015 Jan
TI  - Adverse events and dropouts in Alzheimer's disease studies: what can we learn?
PG  - 24-31
LID - S1552-5260(13)02944-0 [pii]
LID - 10.1016/j.jalz.2013.11.008 [doi]
AB  - BACKGROUND: Interpreting Alzheimer's disease (AD) clinical trial (CT) outcomes is 
      complicated by treatment dropouts and adverse events (AEs). In elderly 
      participants, AE rates, dropouts, and deaths are important considerations as they 
      may undermine the validity of clinical trials. Published discontinuation and 
      safety data are limited. METHODS: Safety data from 1054 placebo-treated 
      participants in IDENTITY and IDENTITY-2, 76-week, Phase 3 AD studies conducted in 
      31 countries, were pooled, annualized, and summarized overall, by country and age 
      group. RESULTS: Median age was 74.2 (interquartile range 67.9-79.5) years; 57.4% 
      were female; and median observation time was 63.2 (interquartile range 41.6-77.4) 
      weeks when study drug dosing was halted. Overall annualized rates for 
      discontinuations, discontinuations due to AEs, serious adverse events (SAEs), and 
      deaths were 21.6% (range 19.6%-24.0%), 8.2% (range 8.1%-8.3%), 12.0%, and 1.7%, 
      respectively. AE and discontinuation rates varied by country and age groups. 
      Fall, pneumonia, and atrial fibrillation AEs were more frequent in the oldest age 
      group. CONCLUSIONS: These annualized placebo safety data provide insight into the 
      course of enrolled patients with mild-to-moderate AD, and are useful in planning 
      longer term trials and in monitoring safety.
CI  - Copyright (c) 2015 The Alzheimer's Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Henley, David B
AU  - Henley DB
AD  - Lilly Research Laboratories, Indianapolis, IN, USA. Electronic address: 
      henleyda@lilly.com.
FAU - Sundell, Karen L
AU  - Sundell KL
AD  - Lilly Research Laboratories, Indianapolis, IN, USA.
FAU - Sethuraman, Gopalan
AU  - Sethuraman G
AD  - Lilly Research Laboratories, Indianapolis, IN, USA.
FAU - Schneider, Lon S
AU  - Schneider LS
AD  - Department of Psychiatry and the Behavioral Sciences and Department of Neurology, 
      University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20140306
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Azepines)
RN  - 0 
      (N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide)
RN  - 0 (Placebos)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Accidental Falls/statistics & numerical data
MH  - Aged
MH  - Aged, 80 and over
MH  - Alanine/adverse effects/*analogs & derivatives
MH  - Alzheimer Disease/*drug therapy
MH  - Atrial Fibrillation/epidemiology
MH  - Azepines/*adverse effects
MH  - Clinical Trials, Phase III as Topic
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neuroimaging/methods
MH  - Patient Dropouts/*statistics & numerical data
MH  - Placebos
MH  - Pneumonia/epidemiology
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse events
OT  - Alzheimer's disease
OT  - Clinical trial methods
OT  - Discontinuations
OT  - Epidemiology
OT  - IDENTITY
OT  - IDENTITY-2
OT  - Safety monitoring
OT  - Serious adverse events
OT  - Site selection
EDAT- 2014/03/13 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/03/12 06:00
PHST- 2013/04/10 00:00 [received]
PHST- 2013/08/28 00:00 [revised]
PHST- 2013/11/18 00:00 [accepted]
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - S1552-5260(13)02944-0 [pii]
AID - 10.1016/j.jalz.2013.11.008 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2015 Jan;11(1):24-31. doi: 10.1016/j.jalz.2013.11.008. Epub 
      2014 Mar 6.