Glossary of terms related to adverse events and sources
| Term | Definition used in our study |
| Clinical study report (CSR) | A special document type originating with drug and device manufacturers for submitting information to regulators (eg, US Food and Drug Administration (FDA), European Medicines Agency). CSRs usually follow intentional guidelines for structure and content, and they often contain detailed summaries of trial design (including the trial protocol and statistical analysis plan) and results.82 |
| Individual patient data (IPD) | A record of variables collected for each participant in a clinical trial (eg, clinical characteristics, scores on tests and questionnaires), usually stored in a database file. |
| Adverse event (AE) | The International Conference on Harmonisation defines an ‘AE’ as ‘any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.’’83 The US FDA and other regulators use this definition.84 85 |
| Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) | The Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) is a terminology developed and used by the FDA for coding, filing and retrieving of post-marketing adverse drug/biologic experience reports.33COSTART was replaced by Medical Dictionary for Regulatory Activities in the late 1990s.34 |
| Preferred term (COSTART symbol) | A 20-character code used to identify events using the COSTART system.33 |
| Mid-level systems | According to the COSTART manual, a mid-level system is a ‘mid-level pathophysiologic classification of COSTART for purposes of categorising and retrieving information based on disease associations.’ ‘This section is hierarchical in arrangement, allowing one to be very general or more specific and is a convenient strategy for searching for drug-induced disease’.33 |
| Body systems | According to the COSTART manual, ‘Essentially anatomic, this body system classification is sometimes the basis of search strategy. The classification is hierarchical in nature.’33 |
| Serious | The US FDA and other regulators consider AEs as ‘serious’ when they lead to or prolong hospitalisation, cause death or disrupt normal life functions.84 85 ‘Serious’ is not synonymous with ‘severe,’ the latter being a descriptive characteristic rather than a regulatory classification. |
| Time under observation | The length of time (eg, days) during which a participant could have reported harms to study investigators, which we estimated for this study using multiple data sources. |
Definitions adapted from previous reports of the MUDS study.7–10 16
MUDS, Multiple Data Sources for Meta-Analysis.