Elsevier

Journal of Clinical Epidemiology

Volume 113, September 2019, Pages 11-19
Journal of Clinical Epidemiology

Original Article
Harms are assessed inconsistently and reported inadequately Part 2: nonsystematic adverse events

https://doi.org/10.1016/j.jclinepi.2019.04.020Get rights and content
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Abstract

Objective

We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials.

Study Design and Setting

We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as “serious.” We recorded whether AEs were grouped by anatomic or physiological system.

Results

Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system.

Conclusion

Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Keywords

Adverse events
Clinical trials
Drug safety
Reporting bias
Open science
Harms

Cited by (0)

Data sharing: Statistical code and datasets are available from the Dryad repository, https://doi.org/10.5061/dryad.mp26fb1.

Funding: This study was supported by contract ME 1303 5785 from the Patient Centered Outcomes Research Institute (PCORI) and funds established for scholarly research on reporting biases at Johns Hopkins University by Greene LLP. The funders were not involved in the design or conduct of the study, article preparation, or the decision to submit the article for publication.

Ethics approval: The study received an exemption from the Johns Hopkins Bloomberg School of Public Health Institutional Review Board (IRB No: 00006324).

Conflict of interest: Up to 2008, K.D. served as an unpaid expert witness for the plaintiffs' lawyers in litigation against Pfizer that provided several gabapentin documents used for this study. Swaroop Vedula was paid by the plaintiffs' attorneys for research assistance provided to K.D. for her work as an expert witness. Greene LLP, a law firm that has represented various clients in litigation against Pfizer, including the case in which K.D. served as an expert witness, provided a fund for scholarly research on reporting biases that partially covered salaries of some investigators performing analysis and interpretation of data.

For the collaborators: Terrie Cowley is President of The TMJ Association, Ltd., which received funding from Pfizer from 2009 to 2011 (for the Campaign to End Chronic Pain in Women) and from Purdue Pharma, L.P. in 2008, 2010, and 2012 to 2016 (to support the TMJ Association science meeting and develop educational materials based on scientific research advances). Peter Doshi was a corecipient of a UK National Institute for Health Research grant (HTA – 10/80/01 Update and amalgamation of two Cochrane reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children—http://www.nets.nihr.ac.uk/projects/hta/108001). Peter Doshi received €1,500 from the European Respiratory Society in support of his travel to the society's September 2012 annual congress in Vienna, where he gave an invited talk on oseltamivir. Peter Doshi gratefully acknowledges the American Association of Colleges of Pharmacy for its funding support ($11,000) for a study to analyze written medical information regarding the possible harms of statins. AACP had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this article. Peter Doshi is also an associate editor of The BMJ and an unpaid member of the IMEDS steering committee at the Reagan-Udall Foundation for the FDA, which focuses on drug safety research.

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These authors contributed equally to this article.