PMID- 23713541
OWN - NLM
STAT- MEDLINE
DCOM- 20140219
LR  - 20191112
IS  - 2212-3911 (Electronic)
IS  - 1574-8863 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Apr
TI  - The detection of adverse events in randomized clinical trials: can we really say 
      new medicines are safe?
PG  - 104-13
AB  - BACKGROUND: While it is well known that randomized controlled trials (RCTs) are 
      usually designed with sufficient sample size and power to detect the efficacy but 
      not safety of a medicine, the extent to which RCTs quantify safety has not been 
      well ascertained. PURPOSE: The aim of this study was to assess the safety data 
      available for five commonly prescribed medicines at the time of marketing. 
      METHODS: Published RCTs for five medicines risperidone, sertraline, donepezil, 
      strontium ranelate and tramadol extended release were identified. All adverse 
      events (AEs) in the trials were independently extracted by two clinical 
      researchers. Using the sample size in the trials, the power to detect the 
      observed difference in AEs rates between the treatment and placebo groups was 
      calculated. A power of 80% or more was deemed adequate to detect AEs; studies 
      with power of < 80% were deemed insufficiently powered to detect AEs. RESULTS: 12 
      RCTs were identified. Six trials were insufficiently powered to detect any of the 
      potential AEs reported. Of the 150 evaluated AEs, the trials were insufficiently 
      powered to detect 81% (122/150) of the AEs reported. For the adverse events that 
      were detected with adequate powered clinical trials, only 53% (10/19) of 
      potentially very common AEs (>/=10%) and 17% (18/106) of potentially common AEs 
      (1%-<10%) were identified. CONCLUSION: Trials are insufficiently powered to 
      detect the majority of adverse events that are reported in clinical trials, even 
      for common adverse events. Observations other than primary efficacy endpoints 
      such as AEs that are not prespecified with adequate power should be treated as 
      hypothesis generating only and not justification of evidence. Claims of safety 
      based on trial evidence not designed for the safety endpoint are often premature.
FAU - Wahab, Izyan A
AU  - Wahab IA
AD  - School of Pharmacy and Medical Sciences, Quality Use of Medicines and Pharmacy 
      Research Centre, Sansom Institute, University of South Australia, GPO Box 2471, 
      Adelaide 5001, South Australia, Australia. ayyiy001@mymail.unisa.edu.au
FAU - Pratt, Nicole L
AU  - Pratt NL
FAU - Kalisch, Lisa M
AU  - Kalisch LM
FAU - Roughead, Elizabeth E
AU  - Roughead EE
LA  - eng
PT  - Journal Article
PL  - United Arab Emirates
TA  - Curr Drug Saf
JT  - Current drug safety
JID - 101270895
SB  - IM
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Endpoint Determination
MH  - Humans
MH  - Randomized Controlled Trials as Topic/*methods
MH  - *Research Design
MH  - Sample Size
EDAT- 2013/05/30 06:00
MHDA- 2014/02/20 06:00
CRDT- 2013/05/30 06:00
PHST- 2012/04/17 00:00 [received]
PHST- 2013/01/29 00:00 [revised]
PHST- 2013/02/13 00:00 [accepted]
PHST- 2013/05/30 06:00 [entrez]
PHST- 2013/05/30 06:00 [pubmed]
PHST- 2014/02/20 06:00 [medline]
AID - CDS-EPUB-20130517-2 [pii]
AID - 10.2174/15748863113089990030 [doi]
PST - ppublish
SO  - Curr Drug Saf. 2013 Apr;8(2):104-13. doi: 10.2174/15748863113089990030.