CIOMS Working Group XII Published Updated Benefit-Risk Guidance for Medicines in 2025

CIOMS, the Council for International Organizations of Medical Sciences, convenes working groups that produce consensus reports on topics in medicines development and safety. Working Group XII was set up to revisit the topic of benefit-risk evaluation, which CIOMS last addressed in its Working Group IV report of 1998, Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals.

The final report, Benefit-risk balance for medicinal products, was published by CIOMS in 2025. The CIOMS publications page lists it at 194 pages with ISBN 978-929036109-1, and a copy held in the University of Tartu repository is dated May 2025 and released under a Creative Commons CC BY-NC-SA 4.0 licence. A draft had been posted for public comment on 12 June 2023. The report states that it reflects the consensus opinion of the working group members, who were drawn from academia, industry and regulatory organisations.

The report was presented at the DIA 2025 Global Annual Meeting in June 2025 in a session titled Newly Released Benefit-Risk Balance for Medicinal Products. The session description stated that the report formulates key principles for life cycle benefit-risk assessments to inform decision-making.

The report starts from the position that a favourable benefit-risk profile must be established before a medicine is marketed, and that the balance must be reassessed periodically after marketing. Its central recommendation is the use of a structured benefit-risk framework that is started early in development and updated across the product life cycle. Its chapters move from an overview of the benefit-risk landscape, through the structured approach and framework, to methodological considerations.

Two emphases distinguish the report from its 1998 predecessor, according to the PSI Benefit-Risk special interest group, which contributed comments on the draft. The first is a move away from treating benefit-risk evaluation as an exercise carried out after the data are available, towards building it into the design and conduct of clinical trials. The second is a pragmatic, patient-centric approach. Conference descriptions of the report refer to a shift from unstructured evaluation towards a more structured, transparent, multi-stakeholder approach, and to the inclusion of patient-centric endpoints that capture both benefit and risk.

Working group minutes published by CIOMS show that the group discussed when quantitative methods add value, including sensitivity analysis where there is uncertainty and multi-criteria decision analysis to handle trade-offs within a benefit-risk question, and how to communicate such methods so that patients can understand them. The final wording of the report’s recommendations on these methods was not reviewed in full for this brief.

Although CIOMS reports are not regulations, they are widely referenced in pharmacovigilance and benefit-risk practice. In a RAPS report on the new approach, Richard Forshee of the US Food and Drug Administration advised companies to establish multidisciplinary teams to develop benefit-risk assessments, and FDA’s Hong Yang described the structured benefit-risk framework as a core part of benefit-risk assessment.

For sponsors, the life cycle emphasis means that benefit-risk thinking should inform endpoint selection, data collection on harms and the identification of key uncertainties during development, rather than being assembled only at the time of a marketing application. For medical writers, a structured framework provides a consistent way to present benefits, risks, uncertainties and their clinical significance in clinical overviews, risk management plans and periodic benefit-risk evaluation reports.

Teams can also use the report to support internal discussion about how patient input, including patient-relevant endpoints, should inform the framework. Because the full report is openly licensed for non-commercial use, it is accessible to academic researchers and smaller sponsors without a subscription.

Regulatory teams should note that the report sits alongside, rather than replaces, regional requirements for benefit-risk presentation, such as the formats used in marketing applications and periodic reports. The value of the CIOMS framework lies in providing a consistent internal method that can then be presented in whichever format a given authority requires. Using one framework from early development onwards also makes it easier to explain how the benefit-risk assessment has evolved as new data emerged, which is often a point of interest in regulatory review.