Aggregate reporting in Pharmacovigilance

Aggregate reporting in pharmacovigilance is the systematic review and evaluation of cumulative safety information collected for a medicinal product over a defined period.

Unlike individual case safety reports (ICSRs), which describe safety information relating to individual patients or cases, aggregate reports examine safety data collectively. This broader evaluation helps identify changes in the safety profile of a medicinal product and supports continuing assessment of its benefits and risks.

Purpose of Aggregate Reporting

The principal purpose of aggregate reporting is to provide an integrated evaluation of safety information accumulated during the development and post-marketing phases of a medicinal product.

Aggregate reporting helps to:

• Evaluate cumulative safety information.
• Identify new or changing safety concerns.
• Assess known and potential risks.
• Evaluate important safety signals.
• Examine changes in the frequency or characteristics of adverse reactions.
• Review relevant clinical and non-clinical safety information.
• Support continuing benefit-risk evaluation.
• Identify whether additional investigation or risk-minimisation measures may be required.

Sources of Information

Aggregate safety reports may incorporate information from multiple sources, depending on the report and stage of the product lifecycle.

These may include:

• Clinical trials
• Spontaneous adverse-event reports
• Scientific and medical literature
• Post-authorisation studies
• Regulatory authority information
• Non-clinical studies where relevant
• Safety signals
• Previous aggregate reports
• Other relevant safety and exposure information

Considering information collectively provides a broader understanding of a medicinal product’s safety profile than assessment of individual cases alone.

Aggregate Reporting During Clinical Development

During clinical development, cumulative safety information concerning an investigational medicinal product is periodically evaluated.

An important aggregate report used during development is the Development Safety Update Report (DSUR).

The DSUR provides an annual review and evaluation of relevant safety information collected during the reporting period and places new safety findings in the context of previous knowledge about the investigational drug.

Aggregate Reporting After Marketing Authorisation

Following marketing authorisation, periodic aggregate reporting supports continued evaluation of the medicinal product’s benefit-risk balance.

Depending on the applicable regulatory framework, reports may include the Periodic Safety Update Report (PSUR) or Periodic Benefit-Risk Evaluation Report (PBRER).

These reports provide a comprehensive and critical evaluation of new and cumulative information relevant to the benefits and risks of the medicinal product.

PSUR and PBRER

The Periodic Benefit-Risk Evaluation Report (PBRER) format was developed through ICH E2C(R2) to provide a harmonised approach to periodic benefit-risk evaluation of marketed medicinal products.

In the European Union, the term PSUR continues to be used in legislation, while the required format and content are based on the PBRER described in ICH E2C(R2).

Therefore, PSUR and PBRER terminology should be understood in the context of the applicable regulatory framework rather than assumed to represent completely unrelated reports.

Reporting Frequency

There is no single reporting frequency that can be applied universally to every aggregate safety report.

The required frequency depends on factors such as:

• Type of aggregate report
• Stage of product development
• Marketing-authorisation status
• Applicable country or regional requirements
• Product-specific regulatory conditions
• Requests from regulatory authorities

For example, DSURs are generally prepared annually during clinical development according to applicable requirements.

For authorised medicines in the European Union, PSUR submission requirements are determined by applicable legislation and the European Union Reference Dates (EURD) list, where relevant. The EURD list specifies submission frequencies and data lock points for listed active substances and combinations.

Pharmacovigilance professionals should therefore verify the current requirements applicable to the specific product and jurisdiction rather than relying on a general reporting schedule.

Regulatory Evaluation

Regulatory authorities use aggregate reports to evaluate whether new risks have emerged or whether the benefit-risk balance of a medicinal product has changed.

The evaluation may result in actions such as:

• Further investigation of a safety concern
• Changes to product information
• Additional pharmacovigilance activities
• Risk-minimisation measures
• Requests for additional studies or data
• Other regulatory action where necessary

Importance of Aggregate Reporting

Aggregate reporting is an essential component of pharmacovigilance because it transforms safety information collected from multiple sources into an integrated assessment of a medicinal product.

Together with individual case reporting, signal management and risk management, aggregate reporting supports the continuing evaluation of medicine safety and benefit-risk balance throughout the product lifecycle.

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