PMID- 30826796
OWN - NLM
STAT- MEDLINE
DCOM- 20200221
LR  - 20210109
IS  - 2044-6055 (Electronic)
IS  - 2044-6055 (Linking)
VI  - 9
IP  - 2
DP  - 2019 Mar 1
TI  - Analysis and reporting of adverse events in randomised controlled trials: a 
      review.
PG  - e024537
LID - 10.1136/bmjopen-2018-024537 [doi]
LID - e024537
AB  - OBJECTIVE: To ascertain contemporary approaches to the collection, reporting and 
      analysis of adverse events (AEs) in randomised controlled trials (RCTs) with a 
      primary efficacy outcome. DESIGN: A review of clinical trials of drug 
      interventions from four high impact medical journals. DATA SOURCES: Electronic 
      contents table of the BMJ, the Journal of the American Medical Association 
      (JAMA), the Lancet and the New England Journal of Medicine (NEJM) were searched 
      for reports of original RCTs published between September 2015 and September 2016. 
      METHODS: A prepiloted checklist was used and single data extraction was performed 
      by three reviewers with independent check of a randomly sampled subset to verify 
      quality. We extracted data on collection methods, assessment of severity and 
      causality, reporting criteria, analysis methods and presentation of AE data. 
      RESULTS: We identified 184 eligible reports (BMJ n=3; JAMA n=38, Lancet n=62 and 
      NEJM n=81). Sixty-two per cent reported some form of spontaneous AE collection 
      but only 29% included details of specific prompts used to ascertain AE data. 
      Numbers that withdrew from the trial were well reported (80%), however only 35% 
      of these reported whether withdrawals were due to AEs. Results presented and 
      analysis performed was predominantly on 'patients with at least one event' with 
      84% of studies ignoring repeated events. Despite a lack of power to undertake 
      formal hypothesis testing, 47% performed such tests for binary outcomes. 
      CONCLUSIONS: This review highlighted that the collection, reporting and analysis 
      of AE data in clinical trials is inconsistent and RCTs as a source of safety data 
      are underused. Areas to improve include reducing information loss when analysing 
      at patient level and inappropriate practice of underpowered multiple hypothesis 
      testing. Implementation of standard reporting practices could enable a more 
      accurate synthesis of safety data and development of guidance for statistical 
      methodology to assess causality of AEs could facilitate better statistical 
      practice.
CI  - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Phillips, Rachel
AU  - Phillips R
AUID- ORCID: 0000-0002-3634-7845
AD  - Faculty of Medicine, School of Public Health, Imperial College London, London, 
      UK.
FAU - Hazell, Lorna
AU  - Hazell L
AD  - Clinical Research, Drug Safety Research Unit, Southampton, UK.
AD  - Department of Pharmacy and Biomedical Sciences, University of Portsmouth, 
      Portsmouth, UK.
FAU - Sauzet, Odile
AU  - Sauzet O
AD  - Epidemiologie & International Public Health, Faculty of Health Sciences, 
      Universitat Bielefeld, Bielefeld, Germany.
FAU - Cornelius, Victoria
AU  - Cornelius V
AD  - Faculty of Medicine, School of Public Health, Imperial College London, London, 
      UK.
LA  - eng
GR  - DRF-2017-10-131/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190301
PL  - England
TA  - BMJ Open
JT  - BMJ open
JID - 101552874
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Drug Therapy
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/etiology
MH  - Humans
MH  - Randomized Controlled Trials as Topic/*methods
PMC - PMC6398660
OTO - NOTNLM
OT  - adverse drug reactions
OT  - adverse events
OT  - harm data
OT  - investigational drug
OT  - randomised controlled trials
OT  - systematic review
COIS- Competing interests: None declared.
EDAT- 2019/03/04 06:00
MHDA- 2020/02/23 06:00
PMCR- 2019/03/01
CRDT- 2019/03/04 06:00
PHST- 2019/03/04 06:00 [entrez]
PHST- 2019/03/04 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/03/01 00:00 [pmc-release]
AID - bmjopen-2018-024537 [pii]
AID - 10.1136/bmjopen-2018-024537 [doi]
PST - epublish
SO  - BMJ Open. 2019 Mar 1;9(2):e024537. doi: 10.1136/bmjopen-2018-024537.