Analysis and reporting of adverse events in randomised controlled trials: a review
Open accessAbstract
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.
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Missing or insufficient reporting of harm-related data is not specific to the probiotic field; similar issues have been reported regarding other interventions.
“Missing or insufficient reporting of harm-related data is not specific to the probiotic field. Similar issues have been reported regarding other interventions.139–142”
From Emerging issues in probiotic safety: 2023 perspectives (2023) · cites this paper as [140]
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- Authors
- Phillips, R., Hazell, L., Sauzet, O., & Cornelius, V.
- Affiliations
- Imperial College London (GB)
- Drug Safety Research Unit (GB)
- Bielefeld University (DE)
- Corresponding author
- Phillips, Rachel
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2019-02
- Volume
- 9
- Issue
- 2
- Pages
- e024537
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC6398660
- OpenAlex
- W2919004480
- Cited by
- 228
- References
- 52
- Citations by year
- 2026: 22 · 2025: 43 · 2024: 26 · 2023: 32 · 2022: 37 · 2021: 30 · 2020: 33 · 2019: 5
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMJ Open (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Research Trainees Coordinating Centre
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Keywords
- adverse events, randomized controlled trials, adverse event reporting, adverse event analysis, spontaneous adverse event reporting, trial withdrawal, multiple comparisons, patient-level analysis, causality assessment, drug safety
- MeSH terms
- Drug Therapy, Humans, Randomized Controlled Trials as Topic, Adverse Drug Reaction Reporting Systems, Drug-Related Side Effects and Adverse Reactions
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