Table 1 Terms related to adverse events (AEs)

 Adverse event (AE)

The International Conference on Harmonisation (ICH) defines an “adverse event” 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” [33]. The U.S. Food and Drug Administration (FDA) and other regulators use this definition [4, 5].

 Non-systematic adverse events

According to The Final Rule [1, 2], “‘non-systematic assessment’ relies on the spontaneous reporting of adverse events, such as unprompted self-reporting by participants”. Non-systematic adverse events may be collected by asking questions such as “Have you noticed any symptoms since your last examination?”.

 Result

In the Multiple Data Sources (MUDS) study, a “result” is a numerical contrast between a treatment and comparison arm (e.g., relative risk, mean difference).

 Serious adverse events

The ICH defines a “serious adverse event” as that which “results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect” [33]. The FDA and other regulators use this definition [4, 5].

 Systematic adverse events

According to The Final Rule [1, 2], “systematic assessment’ involves the use of a specific method of ascertaining the presence of an adverse event (e.g., the use of checklists, questionnaires, specific laboratory tests at regular intervals)”. Like a potential benefit of treatment, a systematic AE can be defined using five elements: (1) domain, (2) specific measurement, (3) specific metric, (4) method of aggregation, and (5) time-point [34]. For example, “proportion of participants with 50% change from baseline to 8 weeks on the Young Mania Rating Scale total score.”

 Clinical study report (CSR)

A comprehensive document, often created by a pharmaceutical manufacturer for submission to a regulator, detailing the design, methods, analyses, and results of a study. Appendices sometimes contain tables of individual patient data, also called “patient data listings”, and study protocols [35].

 Clinical study report synopsis (CSR-synopsis)

A document that summarizes the information contained in a clinical study report. Clinical study report-synopses are much shorter than clinical study reports; the two clinical study report-synopses we examined were each 13 pages in length.

 Individual patient data (IPD)

A table or database in which each record contains data for a single participant [35].

 Non-public sources

In the MUDS study, non-public sources include individual patient data, clinical study reports, and clinical study report-synopses.

 Public sources

In the MUDS study, public sources include journal articles, conference abstracts, commentaries, posters, trial registrations and associated results, and medical reviews and statistical reviews written by the FDA.