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Analysis and reporting of adverse events in randomised controlled trials: a review
  1. Rachel Phillips1,
  2. Lorna Hazell2,3,
  3. Odile Sauzet4,
  4. Victoria Cornelius1
  1. 1 Faculty of Medicine, School of Public Health, Imperial College London, London, UK
  2. 2 Clinical Research, Drug Safety Research Unit, Southampton, UK
  3. 3 Department of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
  4. 4 Epidemiologie & International Public Health, Faculty of Health Sciences, Universität Bielefeld, Bielefeld, Germany
  1. Correspondence to Miss Rachel Phillips; r.phillips{at}


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.

  • randomised controlled trials
  • harm data
  • adverse drug reactions
  • systematic review
  • investigational drug
  • adverse events

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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  • Contributors RP conceived the idea for this review, conducted the search, carried out data extraction and analysis and wrote the manuscript. VC conceived the idea for the review, performed data extraction, critical revision of the manuscript and supervised the project. LH performed data extraction and critical revision of the manuscript. OS performed critical revision of the manuscript.

  • Funding Rachel Phillips is funded by a National Institute for Health Research (NIHR) Doctoral Fellowship.

  • Disclaimer This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available upon reasonable request made to the corresponding author.

  • Patient consent for publication Not required.

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