Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive studyBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g3555 (Published 04 June 2014) Cite this as: BMJ 2014;348:g3555
- Emma Maund, PhD student1,
- Britta Tendal, postdoctoral researcher1,
- Asbjørn Hróbjartsson, senior researcher1,
- Andreas Lundh, physician12,
- Peter C Gøtzsche, professor1
- 1Nordic Cochrane Centre, Rigshospitalet Department 7811, Copenhagen, Denmark
- 2Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Denmark
- Correspondence to: E Maund
- Accepted 5 May 2014
Objective To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports.
Design Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient’s trial identification number. Using the patient’s trial identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report.
Setting 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval.
Data sources Clinical study reports obtained from the EMA in 2011.
Results Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary, especially COSTART. Furthermore, we found one event of suicidal ideation described in narrative text that was absent from tables and adverse event listings of individual patients. The reason for this is unclear, but may be due to the coding conventions used.
Conclusion Data on adverse events in tables in clinical study reports may not accurately represent the underlying patient data because of the medical dictionaries and coding conventions used. In clinical study reports, the listings of adverse events for individual patients and narratives of adverse events can provide additional information, including original investigator reported adverse event terms, which can enable a more accurate estimate of harms.
We thank Julie Borring, Kristine Rasmussen, and Trine Gro Saida for assistance with initial data extraction; the EMA for providing the material and for responding to queries related to the material; and Jesper Krogh for sharing material he obtained from the EMA.
Contributors: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EM and BT contributed to the study concept and design. EM, BT, AH and AL contributed to the acquisition of data. All authors contributed to the analysis and interpretation of data, and drafts of manuscripts. All the authors critically reviewed the manuscript for publication. PCG provided administrative, technical, and material support, and was the study supervisor and guarantor.
Funding: This study is part of a PhD (EM) funded by Rigshospitalets Forskningsudvalg. The funding source had no role in the design and conduct of the study; data collection, management, analysis, and interpretation; preparation, review, and approval of the manuscript; or the decision to submit the paper for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: this study is part of a PhD funded by Rigshospitalets Forskningsudvalg; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: The clinical study reports we used can be obtained from the authors ().
Transparency: The manuscript’s guarantor affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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