PMID- 34954021
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20220609
IS  - 1878-5921 (Electronic)
IS  - 0895-4356 (Linking)
VI  - 144
DP  - 2022 Apr
TI  - Improving the analysis of adverse event data in randomized controlled trials.
PG  - 185-192
LID - S0895-4356(21)00429-7 [pii]
LID - 10.1016/j.jclinepi.2021.12.023 [doi]
AB  - Analyzing treatment harm is vital but problematic with the relatively small 
      sample sizes afforded in randomized controlled trials (RCTs). Good analysis 
      practice for efficacy outcomes are well established but there has been minimal 
      progress for the analysis of adverse events (AEs). In this commentary we examine 
      four key issues for AE analysis. Namely, why harm data in RCTs is undervalued, 
      why AE analysis is difficult, what aspects of current analysis practice are 
      unsatisfactory, and the challenges for selection and interpretation of AEs 
      results in publications. We discuss how the value of harm data from RCTs could be 
      better realized by reframing the research question to one for detecting signals 
      of adverse reactions. We align established good statistical practice to current 
      unsatisfactory practice. We encourage use of Bayesian analyses to enable 
      cumulative assessment of harm across trial research phases and discourage 
      selecting AEs to report based on arbitrary rules. We propose comprehendible 
      summaries to be based on core outcome sets, serious and pre-specified events, and 
      events leading to discontinuation. Analysis of AEs in contemporary clinical 
      trials needs attention to progress. In the following we have outlined immediate, 
      mid and longer-term strategies for trialists to adopt to support a change in 
      practice.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Cornelius, Victoria R
AU  - Cornelius VR
AD  - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 
      Stadium House, 68 Wood Lane, London, W12 7RH. Electronic address: 
      v.cornelius@imperial.ac.uk.
FAU - Phillips, Rachel
AU  - Phillips R
AD  - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 
      Stadium House, 68 Wood Lane, London, W12 7RH.
LA  - eng
PT  - Journal Article
DEP - 20211223
PL  - United States
TA  - J Clin Epidemiol
JT  - Journal of clinical epidemiology
JID - 8801383
SB  - IM
MH  - Humans
MH  - *Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - Adverse Events
OT  - Analysis
OT  - Harm
OT  - Randomized Controlled Trials
OT  - Safety
OT  - Signal Detection
EDAT- 2021/12/27 06:00
MHDA- 2022/04/06 06:00
CRDT- 2021/12/26 20:35
PHST- 2021/09/04 00:00 [received]
PHST- 2021/12/15 00:00 [revised]
PHST- 2021/12/16 00:00 [accepted]
PHST- 2021/12/27 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2021/12/26 20:35 [entrez]
AID - S0895-4356(21)00429-7 [pii]
AID - 10.1016/j.jclinepi.2021.12.023 [doi]
PST - ppublish
SO  - J Clin Epidemiol. 2022 Apr;144:185-192. doi: 10.1016/j.jclinepi.2021.12.023. Epub 
      2021 Dec 23.