Council for International Organizations of Medical Sciences
(CIOMS)

Development Safety Update Report (DSUR): Harmonizing the Format and Content for Periodic Safety Reporting During Clinical Trials

Report of CIOMS Working Group VII

 

 

The Council for International Organizations of Medical Sciences (CIOMS) announces the publication of The Development Safety Update Report (DSUR): Harmonizing the Format and Content for Periodic Safety Reporting During Clinical Trials. Report of CIOMS Working Group VII.

Regular and timely review, appraisal and communication of safety information are critical to risk management during the clinical development of drugs. Whereas the overall goal of a clinical development programme is to characterize the benefit-risk relationship of the product in a particular patient population, the risk to individual trial subjects is a critical consideration during

 

 

 

product development, at a time when the effectiveness of a product is generally uncertain. By conducting an overall appraisal of safety data at regular intervals, risks can be recognised, thoughtfully assessed, and appropriately communicated to all interested stakeholders, to support the safety of clinical trial subjects. Although the regulatory authorities in the EU, US, and some other locations currently require the submission of a periodic safety report during the conduct of clinical trials, usually on an annual basis, there are substantial differences in the format, content, and timing of the different reports. Thus, the CIOMS VII Working Group is proposing an internationally harmonized document, namely, the Development Safety Update Report (DSUR), which is modelled after the Periodic Safety Update Report (PSUR) for marketed products.

The CIOMS VII Working Group hopes that its proposals on the creation of a DSUR and its content and format will be endorsed and universally implemented by all stakeholders.

The CIOMS VII Working Group also envisions a further, more ambitious objective, whereby the DSUR and PSUR are integrated into a single harmonized safety report that would cover a product throughout its lifecycle. Proposals are made for future development of such a document and process.
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The Development Safety Update Report (DSUR):
Harmonizing the Format and Content for Periodic
Safety Reporting During Clinical Trials

Report of CIOMS Working Group VII

CIOMS

Geneva 2006

 

 Table of Contents

Vision

I        Introduction and Overview

 

a.        Rationale for the CIOMS VII Project
b.        Background
c.        Purpose and Objectives of a DSUR

 

II       General Principles for a DSUR

 

a.        Administrative Matters

  • Scope of a DSUR
  • Information Out of Scope
  • When is a DSUR Required
  • Who is Responsible for Preparing a DSUR
  • Recipients of the DSUR
  • Development International Birth Date (DIBD)
  • Periodicity of Reporting
  • A Single DSUR for an Investigational drug
  • Combination Therapy
  • Reference Safety information
  • Relationship of DSUR to Other Documents
  • Confidentiality

b.         Technical Content

  • Sources of Data
  • Patient Exposure
  • Presentation and Evaluation of Clinical Trial Data
  • Modifications to Clinical Trials
  • Overall Assessment

 

III       Development Safety Update Report Model

a.

Title Page

b.

Table of Contents

c.

Executive Summary

d.

Introduction

e.

Worldwide Marketing Authorisation Status

f.

Update on Actions Taken for Safety Reasons

g.

Changes to Reference Safety Information

h.

Inventory and Status of Ongoing and Completed Interventional Clinical Trials

i.

Estimated Patient Exposure in Clinical Trials

j.

Presentation of Safety Data from Clinical Studies

k.

Significant Findings from Interventional Clinical Trials

l.

Observational and Epidemiological Studies

m.

Other Information

n.

Information from Marketing Experience

o.

Late Breaking Information

p.

Overall Safety Evaluation

q.

Summary of Important Risks

r.

New Actions Recommended

s.

Conclusions

t.

Appendices to DSUR



IV




Integrating Pre-Approval (DSUR) with Post-Approval (PSUR) Safety Reporting

 

Appendices

 

  1. Procedure and Membership of CIOMS Working Group VII
  2. Glossary
  3. US vs. EU Annual Safety Reporting Requirements for Investigational Drugs
  4. Sample DSURs
  5. Template for Clinical Study Synopsis
  6. Comparison of DSUR and PSUR Tables of Contents
  7. Proposed Table of Contents for a Model Integrated Periodic Safety Report

 

Vision

 

Regular and timely review, appraisal and communication of safety information are critical to risk management during the clinical development of drugs. Whereas the overall goal of a clinical development programme is to characterize the benefit-risk relationship of the product in a particular patient population, the risk to individual trial subjects is a critical consideration during product development, at a time when the effectiveness of a product is generally uncertain. By conducting an overall appraisal of safety data at regular intervals, risks can be recognised, thoughtfully assessed, and appropriately communicated to all interested stakeholders, to support the safety of clinical trial subjects. Although the regulatory authorities in the EU, US, and some other locations currently require the submission of a periodic safety report during the conduct of clinical trials, usually on an annual basis, there are substantial differences in the format, content, and timing of the different reports. Thus, the CIOMS VII Working Group is proposing an internationally harmonized document, namely, the Development Safety Update Report (DSUR), which is modelled after the Periodic Safety Update Report (PSUR) for marketed products.

The Working Group envisions that such a report would summarize the safety experience and explain any actions proposed or taken for a clinical trial, or for an entire development programme. Although the scopes of the reports would differ, the Group envisions that both commercial and non-commercial sponsors would prepare and submit DSURs. By design, these reports will enable a seamless transition for communicating safety information to relevant stakeholders, starting at the early clinical development stage and, by aligning the DSUR with the PSUR, continuing throughout the post-approval period. It will also lead to enhanced public health protection by ensuring proper focus by all sponsors and clinical investigators on ongoing safety review throughout the life-cycle of a product, while eliminating unnecessarily different, yet redundant requirements.

The CIOMS VII Working Group hopes that its proposals on the creation of a DSUR and its content and format will be endorsed and universally implemented by all stakeholders.

The CIOMS VII Working Group also envisions a further, more ambitious objective, whereby the DSUR and PSUR are integrated into a single harmonized safety report that would cover a product throughout its lifecycle. Proposals are made for future development of such a document and process.