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How to Write a PBRER

Learn how experienced aggregate report authors approach the preparation of a scientifically robust and regulatorily compliant PBRER.

How to Write a PBRER

Introduction

Preparing a Periodic Benefit-Risk Evaluation Report (PBRER) is one of the most intellectually demanding activities performed within pharmacovigilance. Unlike many regulatory documents, the PBRER is not simply a structured compilation of predefined information. It is a cumulative scientific assessment that evaluates whether newly available evidence changes the current understanding of the benefit-risk balance of a medicinal product.

Many new aggregate report authors begin by concentrating on the report template. While understanding the structure of the document is important, experienced authors recognise that successful report preparation begins long before individual sections are drafted. The quality of a PBRER depends upon understanding the scientific questions that the report is intended to answer, identifying the important developments during the reporting interval and constructing a coherent medical assessment supported by evidence.

This article describes the overall approach to writing a PBRER. It explains how experienced authors plan the report, organise information, develop the scientific narrative and maintain consistency throughout the document. Detailed guidance on writing individual sections is provided in separate articles within the "Writing a PBRER" series.

Before Writing Begins

Writing should never begin with an empty document.

Before drafting the report, the lead author should develop a clear understanding of the medicinal product, the previous reporting period and the important developments that have occurred since the last completed PBRER.

This preparatory review commonly includes:

The objective is not to collect information but to understand how the product's scientific story has evolved since the previous reporting period.

Writing Tip

Before opening the report template, ask a simple question:

If I had to explain the most important scientific developments of this reporting period in five minutes, what would they be?

Understanding the Reporting Interval

Not every event occurring during the reporting period deserves equal attention.

Experienced authors distinguish between routine pharmacovigilance activities and developments that materially influence understanding of the medicinal product.

Examples include:

These developments frequently determine the scientific emphasis of the completed report.

The reporting interval should therefore be viewed as a period of scientific evolution rather than a simple chronological collection of events.

Developing the Scientific Narrative

Every well-written PBRER presents a coherent scientific assessment rather than a collection of independent regulatory sections. Although the report follows the structure defined by ICH E2C(R2) and GVP Module VII, the individual sections should not be regarded as isolated documents written independently of one another. Instead, they should progressively develop the scientific argument that ultimately supports the integrated benefit-risk evaluation.

For many inexperienced authors, report preparation begins by opening the template and completing sections sequentially. While this approach may appear logical, it frequently produces reports containing repetition, inconsistent interpretation and conclusions that do not follow naturally from the preceding discussion. Experienced authors adopt the opposite approach. Before drafting begins, they seek to understand the scientific story of the reporting interval and then use the report structure to communicate that assessment clearly.

Developing this narrative requires careful consideration of the product's previous benefit-risk profile, the important developments during the reporting interval and the extent to which those developments modify existing scientific understanding. Some reporting periods are characterised by completion of major signal evaluations. Others may include important regulatory procedures, publication of significant epidemiological studies or completion of post-authorisation safety studies. In many reporting intervals, however, relatively little changes. Recognising that no important scientific developments have occurred is itself an important conclusion and should be communicated clearly.

The scientific narrative should therefore emerge naturally from evaluation of the available evidence rather than being constructed to fit a predetermined conclusion. Every major discussion within the report should contribute to explaining how the medicinal product's benefit-risk profile has evolved during the reporting interval.

Writing Tip

Before drafting the first section, write a one-page summary describing the major scientific messages of the reporting interval. If this summary cannot be written clearly, additional review of the underlying evidence is usually required before drafting begins.

Reading Before Writing

Preparation of a PBRER involves considerably more reading than writing. Experienced authors spend substantial time reviewing source documents before producing the first draft of the report. This preparatory review establishes the scientific context and helps identify issues requiring detailed discussion later in the writing process.

The previous PBRER should always be reviewed carefully. It establishes the baseline against which the current reporting interval will be assessed. Important identified risks, potential risks, ongoing pharmacovigilance activities and previous regulatory commitments should all be understood before new information is interpreted. Without this context, it becomes difficult to determine whether newly available evidence genuinely changes existing understanding or simply confirms previously recognised observations.

Authors should also review completed signal assessments, important Individual Case Safety Reports where appropriate, relevant literature publications, post-authorisation study reports, regulatory correspondence and product information changes. These documents often explain the rationale behind important safety decisions and provide essential context for the cumulative assessment presented within the PBRER.

Reading source documents should not become an exercise in collecting information for inclusion within the report. Instead, the objective is to understand the evolution of the medicinal product's safety profile and identify the issues that will shape the scientific assessment.

Identifying the Key Scientific Questions

Every reporting interval raises a series of scientific questions that should be addressed during preparation of the PBRER. These questions differ between medicinal products and between reporting periods, reflecting differences in therapeutic area, product maturity and newly available evidence.

Examples include whether newly available information modifies understanding of an important identified risk, whether recently completed signal evaluations support changes to product information, whether additional risk minimisation activities should be considered or whether new efficacy information influences interpretation of the overall benefit-risk balance.

These questions should be identified before drafting individual sections because they determine the emphasis of the report. A reporting interval dominated by evaluation of an important hepatic safety concern will necessarily differ from one focused on pregnancy exposure or long-term effectiveness. Although the report template remains unchanged, the scientific discussion should reflect the issues that are genuinely important for the medicinal product during the reporting period.

Experienced authors frequently maintain a working list of these key scientific questions throughout report preparation. As drafting progresses, they confirm that each important question has been addressed adequately and that the final conclusions remain consistent with the evidence presented throughout the report.

Inspection Insight

Regulatory assessors frequently focus their review on the principal scientific issues affecting the medicinal product during the reporting interval. Reports that identify and discuss these issues clearly are generally easier to assess than reports that give equal emphasis to every item of information regardless of clinical importance.

Writing Scientifically Rather Than Descriptively

One of the defining characteristics of an experienced aggregate report author is the ability to distinguish between description and scientific interpretation.

Descriptive writing explains what happened. Scientific writing explains why it matters.

For example, simply stating that a number of Individual Case Safety Reports describing a particular adverse reaction were received during the reporting interval provides factual information but contributes little to understanding the medicinal product's safety profile. A scientific discussion places those reports within their clinical context by considering cumulative experience, exposure, consistency with existing knowledge, biological plausibility, signal evaluation outcomes and any resulting impact on the overall benefit-risk balance.

Throughout the report, descriptive information should support scientific interpretation rather than replace it. Tables, cumulative summaries and case listings provide important evidence, but they should not become the principal message of the report. The author's responsibility is to interpret the available evidence objectively and explain its regulatory significance.

This distinction is reflected throughout ICH E2C(R2), which emphasises periodic benefit-risk evaluation rather than periodic safety description. Although comprehensive presentation of data remains important, the value of the report ultimately depends upon the quality of the scientific assessment rather than the volume of information presented.

Maintaining Consistency Throughout the Report

Consistency is one of the defining characteristics of a high-quality PBRER. Regulatory assessors expect the report to present a single coherent scientific assessment rather than a collection of independently written sections. Every major conclusion should therefore be supported consistently throughout the document, with each section contributing to the overall understanding of the medicinal product's benefit-risk balance.

Maintaining this consistency becomes increasingly challenging as reports become larger and involve contributions from multiple subject matter experts. Different authors may prepare different sections, data may originate from several pharmacovigilance systems and scientific opinions may evolve during preparation of the report. Without careful editorial oversight, these factors can lead to duplication, contradictory statements or conclusions that are not adequately supported by the preceding discussion.

Consistency should therefore be considered at several levels. Terminology should remain uniform throughout the report. Safety concerns should be described using consistent language. Important identified risks, important potential risks and missing information should be discussed consistently with the current Risk Management Plan where applicable. Similarly, product information updates, completed signal evaluations and important regulatory actions should be reflected wherever they influence subsequent discussions.

Scientific consistency is equally important. If a completed signal evaluation concludes that available evidence does not support a causal relationship, later discussions should remain aligned with that conclusion unless additional evidence is introduced. Likewise, if new information significantly changes understanding of an identified risk, that change should be reflected consistently throughout the report rather than appearing in only one section.

Writing Tip

After completing the first full draft, read the report from beginning to end as though it had been written by another author. Concentrate on the flow of the scientific argument rather than grammar or formatting. Inconsistencies become much easier to identify when the report is reviewed as a complete document.

Working with Subject Matter Experts

Preparation of a PBRER is rarely the responsibility of a single individual. Aggregate report authors work closely with colleagues responsible for signal management, epidemiology, regulatory affairs, clinical development, pharmacovigilance operations and other specialist functions. Each contributor provides expertise that supports the overall scientific assessment.

The lead author should recognise, however, that the objective is not simply to assemble independent contributions into a single document. Every contribution should support a consistent scientific narrative and should be interpreted within the broader context of the report. Subject matter experts provide specialist knowledge, but responsibility for maintaining coherence across the completed document generally rests with the lead medical reviewer or aggregate report author.

When reviewing contributions from different functions, authors should look beyond technical accuracy. They should also consider whether terminology is consistent, whether discussions duplicate information presented elsewhere and whether conclusions remain aligned with the overall benefit-risk assessment.

This process often requires dialogue between contributors. Apparent differences in interpretation may reflect differences in perspective rather than genuine disagreement. Resolving these issues before the report enters formal quality review generally produces a more coherent final document.

Industry Best Practice

Many organisations hold scientific review meetings after completion of the initial draft to discuss significant safety issues, resolve differences in interpretation and ensure that the integrated benefit-risk assessment reflects a shared understanding of the available evidence. Although this is not a regulatory requirement, it frequently improves scientific consistency.

Reviewing the First Complete Draft

Completion of the first draft represents the beginning of scientific review rather than the end of report preparation. At this stage, the author should temporarily step away from individual sections and evaluate the report as a complete scientific assessment.

Several questions are useful during this review.

Does the report explain what changed during the reporting interval?

Are the most important scientific developments given appropriate emphasis?

Do the conclusions follow logically from the evidence presented?

Has important information been discussed more than once without adding value?

Have contradictory statements developed during preparation of different sections?

Could an assessor unfamiliar with the product understand why the conclusions have been reached?

The purpose of this review is not to identify typographical errors or formatting inconsistencies. Those issues can be addressed during later quality control. Instead, the objective is to confirm that the report communicates a coherent, balanced and scientifically defensible assessment.

Experienced authors frequently find that relatively small revisions made at this stage substantially improve the clarity of the final report.

Common Mistakes Made by New Aggregate Report Authors

Most new aggregate report authors encounter similar challenges during their first few reporting cycles. Recognition of these common difficulties can help authors avoid many of the deficiencies observed during internal quality review and regulatory assessment.

A common mistake is allowing the report to become excessively descriptive. Authors sometimes assume that inclusion of more information automatically improves report quality. In practice, lengthy descriptions without corresponding interpretation often make the report more difficult to assess and obscure the principal scientific messages.

Another frequent problem is treating each section as an independent writing exercise. This approach often results in repetition, inconsistent terminology and conclusions that differ between sections. The report should instead be developed as a single scientific assessment in which each chapter contributes to the overall evaluation.

Some authors also give equal prominence to every observation identified during the reporting interval. Experienced reviewers recognise that not all findings have the same scientific importance. The report should reflect the relative significance of available evidence, giving appropriate emphasis to issues that materially influence the benefit-risk assessment.

Finally, new authors sometimes hesitate to acknowledge uncertainty. Scientific uncertainty is an expected feature of pharmacovigilance. Regulators generally prefer transparent discussion of remaining uncertainties to overly confident conclusions that are not fully supported by the available evidence.

Common Mistake

Editing individual sections repeatedly before the overall scientific assessment has been developed. Early perfection of isolated sections often creates inconsistency later when the report evolves during review.

Performing the Final Medical Review

The final medical review represents the last opportunity to evaluate the PBRER as a complete scientific assessment before regulatory submission. By this stage, factual corrections, section ownership and routine editorial revisions should already have been completed. The objective of the final review is not to identify typographical errors but to determine whether the report communicates a balanced, internally consistent and scientifically defensible assessment of the medicinal product's benefit-risk profile.

Experienced aggregate physicians often approach the final review as though they were reading the report for the first time. Rather than concentrating on individual paragraphs, they focus on the overall scientific narrative. They consider whether the report clearly explains the important developments during the reporting interval, whether the evidence has been interpreted appropriately and whether the conclusions are supported consistently throughout the document.

The reviewer should also assess whether the report remains proportionate. Minor observations should not overshadow clinically important findings, while major developments should receive sufficient discussion to explain their scientific and regulatory significance. A balanced report reflects the relative importance of the available evidence rather than allocating equal attention to every item of information collected during the reporting period.

Another important objective is to ensure that the report presents a coherent scientific position. Conclusions reached within the integrated benefit-risk evaluation should already be apparent from the preceding discussions rather than appearing unexpectedly at the end of the report. Similarly, recommendations regarding product information, pharmacovigilance activities or future monitoring should arise naturally from the cumulative evidence presented throughout the document.

Writing Tip

During the final review, avoid asking whether every section has been completed. Instead ask whether the report convincingly answers the central regulatory question:

Does the cumulative evidence support the conclusion that the benefit-risk balance remains favourable, or has the current understanding of the product changed?

A High-Level Quality Review Checklist

Although individual organisations establish their own quality review procedures, experienced authors commonly consider a number of high-level questions before final approval.

Has the report clearly identified the important scientific developments during the reporting interval?

Is the interpretation of the evidence balanced and supported by the available data?

Are the discussions consistent with completed signal evaluations, current product information and the Risk Management Plan where applicable?

Are important conclusions reflected consistently throughout the report?

Has unnecessary repetition been minimised?

Have limitations of the available evidence been acknowledged where appropriate?

Does the integrated benefit-risk evaluation logically follow from the preceding scientific discussions?

Would an independent medical reviewer unfamiliar with the product understand how the conclusions were reached?

These questions should complement, rather than replace, formal organisational quality control procedures. They encourage the reviewer to assess the report as a scientific document rather than simply confirming compliance with a reporting template.

Inspection Insight

During regulatory assessment or pharmacovigilance inspection, reviewers may evaluate not only the completed PBRER but also the organisation's ability to explain and justify the scientific conclusions contained within the report. A well-reasoned assessment is generally easier to defend than one relying primarily on descriptive summaries.

Becoming a Better Aggregate Report Author

Developing expertise in aggregate report writing requires continuous exposure to different medicinal products, therapeutic areas and regulatory assessments. Although familiarity with ICH E2C(R2), GVP Module VII and organisational procedures provides the necessary regulatory foundation, experience is gained by repeatedly evaluating evidence, defending scientific conclusions and learning from regulatory feedback.

New authors are encouraged to read completed PBRERs critically rather than simply using them as templates. Consider why particular discussions have been included, how evidence has been interpreted and whether the conclusions follow logically from the available data. Comparing reports prepared for different products or therapeutic areas also demonstrates how the same regulatory framework can accommodate substantially different scientific discussions.

Participation in peer review is equally valuable. Reviewing reports prepared by experienced colleagues exposes authors to alternative approaches to scientific reasoning, writing style and evidence integration. Over time, this develops the ability to recognise both strong scientific arguments and common weaknesses before they appear in one's own work.

Ultimately, successful aggregate report authors recognise that writing is only one component of the role. Their primary responsibility is to evaluate evidence objectively, apply sound medical judgement and communicate scientific conclusions clearly enough to support regulatory decision-making.

Continue Reading

This article provides an overview of the principles involved in writing a Periodic Benefit-Risk Evaluation Report. The following articles examine individual aspects of report preparation in greater detail.

Recommended next articles:

Glossary

Aggregate Report

A regulatory document that evaluates cumulative safety or benefit-risk information over a defined reporting period.

Benefit-Risk Evaluation

The structured scientific assessment of whether the therapeutic benefits of a medicinal product continue to outweigh its identified and potential risks.

Integrated Assessment

The process of combining evidence from multiple pharmacovigilance activities into a single scientific evaluation.

Medical Review

The critical scientific evaluation of available evidence performed by appropriately qualified medical reviewers before regulatory submission.

Scientific Narrative

The logical progression of evidence and interpretation that explains how the report's conclusions have been reached.

References

Primary Regulatory References

  1. ICH E2C(R2): Periodic Benefit-Risk Evaluation Report.

  2. EMA Good Pharmacovigilance Practices (GVP) Module VII – Periodic Safety Update Report.

  3. Directive 2001/83/EC, as amended.

  4. Regulation (EC) No 726/2004, as amended.

  5. Commission Implementing Regulation (EU) No 520/2012.

EMA Guidance

  1. EMA Questions and Answers on Periodic Safety Update Reports.

  2. EMA PSUR Repository Guidance.

  3. EMA EURD List.

  4. EMA Procedural Guidance for PSUR Single Assessment.

Performing the Final Medical Review

The final medical review represents the last opportunity to evaluate the PBRER as a complete scientific assessment before regulatory submission. By this stage, factual corrections, section ownership and routine editorial revisions should already have been completed. The objective of the final review is not to identify typographical errors but to determine whether the report communicates a balanced, internally consistent and scientifically defensible assessment of the medicinal product's benefit-risk profile.

Experienced aggregate physicians often approach the final review as though they were reading the report for the first time. Rather than concentrating on individual paragraphs, they focus on the overall scientific narrative. They consider whether the report clearly explains the important developments during the reporting interval, whether the evidence has been interpreted appropriately and whether the conclusions are supported consistently throughout the document.

The reviewer should also assess whether the report remains proportionate. Minor observations should not overshadow clinically important findings, while major developments should receive sufficient discussion to explain their scientific and regulatory significance. A balanced report reflects the relative importance of the available evidence rather than allocating equal attention to every item of information collected during the reporting period.

Another important objective is to ensure that the report presents a coherent scientific position. Conclusions reached within the integrated benefit-risk evaluation should already be apparent from the preceding discussions rather than appearing unexpectedly at the end of the report. Similarly, recommendations regarding product information, pharmacovigilance activities or future monitoring should arise naturally from the cumulative evidence presented throughout the document.

Writing Tip

During the final review, avoid asking whether every section has been completed. Instead ask whether the report convincingly answers the central regulatory question:

Does the cumulative evidence support the conclusion that the benefit-risk balance remains favourable, or has the current understanding of the product changed?

A High-Level Quality Review Checklist

Although individual organisations establish their own quality review procedures, experienced authors commonly consider a number of high-level questions before final approval.

Has the report clearly identified the important scientific developments during the reporting interval?

Is the interpretation of the evidence balanced and supported by the available data?

Are the discussions consistent with completed signal evaluations, current product information and the Risk Management Plan where applicable?

Are important conclusions reflected consistently throughout the report?

Has unnecessary repetition been minimised?

Have limitations of the available evidence been acknowledged where appropriate?

Does the integrated benefit-risk evaluation logically follow from the preceding scientific discussions?

Would an independent medical reviewer unfamiliar with the product understand how the conclusions were reached?

These questions should complement, rather than replace, formal organisational quality control procedures. They encourage the reviewer to assess the report as a scientific document rather than simply confirming compliance with a reporting template.

Inspection Insight

During regulatory assessment or pharmacovigilance inspection, reviewers may evaluate not only the completed PBRER but also the organisation's ability to explain and justify the scientific conclusions contained within the report. A well-reasoned assessment is generally easier to defend than one relying primarily on descriptive summaries.

Becoming a Better Aggregate Report Author

Developing expertise in aggregate report writing requires continuous exposure to different medicinal products, therapeutic areas and regulatory assessments. Although familiarity with ICH E2C(R2), GVP Module VII and organisational procedures provides the necessary regulatory foundation, experience is gained by repeatedly evaluating evidence, defending scientific conclusions and learning from regulatory feedback.

New authors are encouraged to read completed PBRERs critically rather than simply using them as templates. Consider why particular discussions have been included, how evidence has been interpreted and whether the conclusions follow logically from the available data. Comparing reports prepared for different products or therapeutic areas also demonstrates how the same regulatory framework can accommodate substantially different scientific discussions.

Participation in peer review is equally valuable. Reviewing reports prepared by experienced colleagues exposes authors to alternative approaches to scientific reasoning, writing style and evidence integration. Over time, this develops the ability to recognise both strong scientific arguments and common weaknesses before they appear in one's own work.

Ultimately, successful aggregate report authors recognise that writing is only one component of the role. Their primary responsibility is to evaluate evidence objectively, apply sound medical judgement and communicate scientific conclusions clearly enough to support regulatory decision-making.

Continue Reading

This article provides an overview of the principles involved in writing a Periodic Benefit-Risk Evaluation Report. The following articles examine individual aspects of report preparation in greater detail.

Recommended next articles:

Glossary

Aggregate Report

A regulatory document that evaluates cumulative safety or benefit-risk information over a defined reporting period.

Benefit-Risk Evaluation

The structured scientific assessment of whether the therapeutic benefits of a medicinal product continue to outweigh its identified and potential risks.

Integrated Assessment

The process of combining evidence from multiple pharmacovigilance activities into a single scientific evaluation.

Medical Review

The critical scientific evaluation of available evidence performed by appropriately qualified medical reviewers before regulatory submission.

Scientific Narrative

The logical progression of evidence and interpretation that explains how the report's conclusions have been reached.

References

Primary Regulatory References

  1. ICH E2C(R2): Periodic Benefit-Risk Evaluation Report.

  2. EMA Good Pharmacovigilance Practices (GVP) Module VII – Periodic Safety Update Report.

  3. Directive 2001/83/EC, as amended.

  4. Regulation (EC) No 726/2004, as amended.

  5. Commission Implementing Regulation (EU) No 520/2012.

EMA Guidance

  1. EMA Questions and Answers on Periodic Safety Update Reports.

  2. EMA PSUR Repository Guidance.

  3. EMA EURD List.

  4. EMA Procedural Guidance for PSUR Single Assessment.

Related Articles

Periodic Benefit-Risk Evaluation Reports (PBRER)

A definitive guide to Periodic Benefit-Risk Evaluation Reports for pharmacovigilance professionals, medical reviewers and QPPVs.

Estimating Patient Exposure in Pharmacovigilance

Learn how patient exposure is estimated for PBRERs, PADERs, DSURs, signal detection, PASS and benefit-risk evaluation.

Understanding the Structure of a PBRER

A guide to understanding why the PBRER is organised as it is and how its sections work together to support the integrated benefit-risk evaluation.

Last reviewed: 2026-06-11