The format we inherited

The Periodic Benefit-Risk Evaluation Report, defined by ICH E2C(R2) and its regulatory implementations — the PSUR in the EU, the PBRER globally — is the primary vehicle through which marketing authorization holders communicate cumulative safety experience to regulators. It is submitted on defined schedules, covers defined data lock points, and follows a defined structure.

The format has been largely unchanged since the 2012 ICH E2C(R2) guideline. It was designed for a pharmacovigilance world where safety data came from two primary sources: spontaneous reports from post-marketing surveillance and adverse event data from clinical trials. The PBRER structure reflects this: sections for ICSR summaries, clinical trial safety updates, literature reviews, and an integrated benefit-risk analysis.

What has changed

The pharmacovigilance landscape has evolved substantially since 2012. Real-world evidence from electronic health records and claims databases now provides population-level safety data that spontaneous reporting cannot. AI-augmented signal detection tools are identifying patterns in unstructured data. Patient-reported outcome measures are capturing adverse-event experiences that clinician coding misses. Genomic and biomarker data are enabling precision safety assessments.

None of these data sources have a standardized home within the current PBRER structure. The result is that PBRER authors are retrofitting new data types into a format designed for an earlier era, with inconsistent approaches across companies and products.

The efficiency question

Beyond the structural limitations, there is a practical efficiency concern. Industry survey data suggest that 60-70% of the effort involved in PBRER preparation is spent on data compilation, formatting, and quality control rather than on the safety analysis that is the document's purpose. For companies managing dozens or hundreds of products, the cumulative PBRER burden represents a significant diversion of pharmacovigilance expertise from signal evaluation and risk management to document preparation.

The question is whether the periodic reporting model itself needs rethinking, or whether the PBRER format simply needs updating to accommodate new data sources. Both conversations are underway within the ICH framework, but progress is measured in years rather than months.