Toward a Framework for Case Identification in Pharmacovigilance: Not All Reports are Created Equal.

BACKGROUND

Retrieval of adverse event reports based on coded drug-event co-occurrence enables large-scale pharmacovigilance analyses but yields candidate reports rather than clinically adjudicated cases. Without explicit case identification, heterogeneous reports may be combined within the same case series and misinterpreted in downstream analyses.

AIM: The aim of the study was to develop a structured framework for distinguishing clinically meaningful cases from candidate reports retrieved through coded drug-event co-occurrence, and to illustrate its application across information-rich and routine-review conditions.

METHODS

We conducted a sequential framework-development study using two case studies. Drug-induced impulsivity was used to iteratively develop and refine the framework under information-rich conditions. Drug-induced suicidality was used to examine its application under routine-review conditions with variable information availability and explicit classification of nonassessability.

RESULTS

In case 1, nonrelevant reports were more frequent for drugs with uncertain or no established evidence (~ 20-40%) than for drugs with established causal roles (4%). The framework assessed relevance across exposure, event, the drug-event relationship, and setting/population. Reports retained as relevant were further characterized by reporter suspicion and evidentiary qualifiers supporting or weakening suspicion. Reports with explicit suspicion more often contained supportive qualifiers. In case 2, application of the framework classified 69% of reports as nonrelevant and 17% as nonassessable.

CONCLUSIONS

In pharmacovigilance, retrieval is not equivalent to case identification. Relevance depends on whether exposure, event, their relationship, and context correspond to the clinical question being investigated. Explicit case definitions and transparent adjudication make this distinction systematic and auditable. Independent evaluation of the framework is needed to establish its reproducibility and transferability across pharmacovigilance questions.