PMID- 25311571
OWN - NLM
STAT- MEDLINE
DCOM- 20160309
LR  - 20211021
IS  - 1432-1459 (Electronic)
IS  - 0340-5354 (Linking)
VI  - 262
IP  - 6
DP  - 2015 Jun
TI  - Characterization of the adverse events profile of placebo-treated patients in 
      randomized controlled trials on drug-resistant focal epilepsies.
PG  - 1401-6
LID - 10.1007/s00415-014-7535-0 [doi]
AB  - In epilepsy trials a substantial proportion of patients receiving placebo has 
      some improvement or experience adverse events (AEs) which match those related to 
      active drug. The characterization of factors influencing these responses is 
      crucial for a better comprehension of study results and to improve design of new 
      trials. Seventy-one placebo-controlled, double-blind trials in drug-resistant 
      focal epilepsies has been selected. The effect of multiple factors on some 
      outcome measures were explored using a meta-regression model. For subjective and 
      objective AEs, risk difference (RD) was calculated and entered in an inverse 
      variance-weighted linear meta-regression model as independent variable to 
      evaluate the relationship with data reported in placebo-treated patients. The 
      number of study arms influence the percentage of patients withdrawing because of 
      AEs and the highest dose of the experimental drug used in each RCT correlates 
      with withdrawal because of AEs and with subjective AEs. Higher titration speed is 
      associated with lower percentages of responders and higher reporting of both 
      objective and subjective AEs. The correlation between proportions of 
      placebo-treated patients with subjective and objective neurological AEs and 
      relative RD, was significant (P = 0.002 r = 0.364 and P < 0.001 r = 0.650, 
      respectively). Efficacy and tolerability outcomes of the placebo groups are 
      intrinsically tied to the trial methodology and to the outcomes observed in 
      patients treated with the active drug. The correlation for objective and 
      subjective AEs between RD and the placebo-treated patients suggest that 
      investigators are influenced by factors which operate within each specific trial.
FAU - Giovannelli, Fabio
AU  - Giovannelli F
AD  - Unit of Neurology Department of Medicine Florence Health Authority, San Giovanni 
      di Dio Hospital, Via Di Torregalli n 3, 50143, Florence, Italy, 
      fabio.giovannelli@unifi.it.
FAU - Zaccara, Gaetano
AU  - Zaccara G
FAU - Cincotta, Massimo
AU  - Cincotta M
FAU - Loiacono, Giulia
AU  - Loiacono G
FAU - Verrotti, Alberto
AU  - Verrotti A
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20141014
PL  - Germany
TA  - J Neurol
JT  - Journal of neurology
JID - 0423161
RN  - 0 (Placebos)
SB  - IM
MH  - Databases, Bibliographic/statistics & numerical data
MH  - Drug Resistant Epilepsy/*therapy
MH  - Humans
MH  - Nocebo Effect
MH  - Outcome Assessment, Health Care
MH  - Placebo Effect
MH  - Placebos/*adverse effects
MH  - *Randomized Controlled Trials as Topic
EDAT- 2014/10/15 06:00
MHDA- 2016/03/10 06:00
CRDT- 2014/10/15 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2014/10/07 00:00 [accepted]
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
AID - 10.1007/s00415-014-7535-0 [doi]
PST - ppublish
SO  - J Neurol. 2015 Jun;262(6):1401-6. doi: 10.1007/s00415-014-7535-0. Epub 2014 Oct 
      14.