Biotech Leaders: If You’re Still Treating Benefit-Risk as a Submission Box Check, You’re Already Behind
In May 2025, the Council for International Organizations of Medical Sciences (CIOMS) released a monumental update to its benefit-risk assessment guidance: the Working Group XII report, Benefit-Risk Balance for Medicinal Products.
At nearly 200 pages, this report isn’t light reading—but for Biopharma teams navigating regulatory pathways, patient-centric innovation, and limited internal bandwidth, it's a must-understand document. It does more than update the 1998 CIOMS IV report—it reframes the entire conversation around benefit-risk as a structured, continuous, multidisciplinary, and patient-inclusive process.
This post breaks down what’s new, what it means for Biopharma teams, and how you can start applying these insights right now.
What’s New: CIOMS XII in Summary
Here’s the foundational shift: benefit-risk assessment (BRA) is no longer a discrete moment—it’s a lifecycle discipline.
The report introduces or reinforces several key ideas:
1. Lifecycle Thinking
BRA starts before the first human trial and continues long after market approval. This includes:
Preclinical planning
Protocol development
Real-world postmarketing evaluation
Why it matters: Teams that treat BRA as a submission requirement will fall behind those treating it as a strategic lens for development.
2. Structured Benefit-Risk Framework (SBRF)
The report presents a framework with consistent components across the product lifecycle:
Therapeutic context
Product profile (benefits, risks, uncertainties)
Risk management strategies
Overall assessment and trade-offs
These are to be captured in a Benefit-Risk Assessment Document (BRAD)—a living document that matures with your program
Why it matters: Regulatory agencies (EMA, FDA, PMDA) are converging on structured, transparent evaluations. A well-maintained BRAD becomes a source of truth for internal alignment and submission strategy.
3. Patient Voice as Core Data
Patients aren’t passive recipients—they’re considered co-evaluators of benefit and risk. The report strongly encourages integrating:
Patient-Reported Outcomes (PROs)
Patient preference studies
Engagement in endpoint selection and trial design
Why it matters: These perspectives shape regulatory decision-making, especially in areas with tight trade-offs or unmet needs
4. Expanded Use of Quantitative Tools
From Multi-Criteria Decision Analysis (MCDA) to Desirability of Outcome Ranking (DOOR), the report recognizes that qualitative frameworks aren't always enough—especially in:
Complex trade-offs
Subgroup analyses
Uncertainty modeling
Why it matters: For many lean Biopharma companies, these tools have felt out of reach. The report reframes them as occasional but powerful options, not mandatory for every scenario.
5. Special Situations, Special Approaches
BRA must adapt in contexts such as:
Rare diseases
ATMPs
Accelerated approvals
Emergency use authorizations
Non-prescription products
The report offers tailored considerations for each, including alternative endpoints, real-world comparators, and modified risk frameworks
Why it matters: If your pipeline includes anything “nonstandard,” CIOMS XII offers a roadmap for evidence generation and risk communication.
Strategic Insights: What It Means for Biopharma Teams
Let’s dig deeper into how these ideas can—and should—change the way Biopharma companies approach benefit-risk evaluation, especially under resource constraints.
1. Start Your BRAD Earlier Than You Think
Benefit-Risk Framework Core Dimensions
Source: CIOMS Working Group XII
Think of the BRAD like you would a target product profile (TPP): iterative, strategic, and critical for internal decision-making. If you’re waiting until post-Phase 2 to write it, you’ve already missed multiple chances to align teams, communicate risk posture, and capture evolving thinking.
Recommendation: Initiate a living BRAD by the end of your preclinical phase and treat it as a “benefit-risk memory” that grows with your program.
2. Integrate Patient Voice Early—But Strategically
You don’t need a full-blown preference study for every product. But CIOMS XII is clear: patient perspectives matter more than ever. This isn’t just about ethics—it’s about relevance, differentiation, and de-risking submission strategy.
Recommendation: Use qualitative interviews or smaller-scale preference elicitation to define unmet needs, shape endpoints, and prioritize benefits and risks from the patient’s lens.
3. Use Frameworks to Fuel Clinical Design, Not Just Reg Docs
BRA isn’t just for regulatory teams. The SBRF framework can help clinical ops and medical teams ask:
Are we measuring the right benefits for the right population?
How do our comparators align with real-world standards?
Which risks need proactive mitigation, not just passive monitoring?
Recommendation: Involve regulatory, clinical, safety, and patient engagement leads in building your value tree and visual risk narratives early—especially before finalizing Phase 2/3 protocols.
4. Quantitative BRA Isn’t Overkill—It’s Competitive Intelligence
You don’t need MCDA for every submission. But when you do face uncertainty, tight margins, or diverse stakeholder opinions, quant tools like DOOR, value trees, or waterfall plots give you the upper hand—in review rooms and in internal debates.
Recommendation: Identify “complex trade-off” points in your program. Use visuals and basic structured models to communicate options early to regulators and investors alike.
5. Visualize Your Story—For Reviewers and Your Team
The report highlights multiple visual tools: forest plots, tornado diagrams, heatmaps, value trees. These aren’t academic—they help:
Get teams on the same page
Make trade-offs transparent
Build better submission narratives
Recommendation: Add benefit-risk graphics into internal pitch decks, trial design discussions, and safety reviews—not just regulatory submissions.
Looking Ahead: This Isn’t Just a Regulatory Shift—It’s a Culture Shift
What CIOMS XII really pushes is a new organizational mindset: benefit-risk isn’t a hurdle to clear, it’s a language for cross-functional alignment.
Medical affairs can use BRADs to shape communication and HCP education.
Clinical leads can use value trees to defend endpoint choices.
Execs and investors can track how product maturity reduces risk and increases clarity.
Patients can finally see their input reflected in decision-making.
In short, a good BRA isn’t just “FDA-friendly.” It’s a strategic asset for every stakeholder.
TL;DR: What Should You Do Right Now?
Download the CIOMS XII report—even just the Executive Summary and Chapter 2.
Start a BRAD, even if it’s scrappy. Align key stakeholders around it.
Engage patients early, with light-touch methods if needed.
Visualize your benefit-risk logic—for internal clarity and external storytelling.
Plan for special situations—if you’re doing anything innovative, CIOMS XII probably has guidance for it.
Want Help Getting Started?
Whether you’re drafting your first BRAD, designing a Phase 2 trial that reflects patient priorities, or thinking about how to visually present risk trade-offs to a review board—we can help. Reach out to chat about how we’re embedding these principles into consulting, trial planning, and regulatory strategy for Biopharma teams.
Let’s make benefit-risk not just a check-the-box requirement, but a strategic advantage.
References
1. CIOMS Working Group XII. Benefit-Risk Balance for Medicinal Products. Geneva: Council for International[BK1] Organizations of Medical Sciences (CIOMS), 2025. https://doi.org/10.56759/gwfz1791
2. U.S. Food & Drug Administration (FDA). Benefit-Risk Assessment in Drug Regulatory Decision-Making. September 2021. https://www.fda.gov/files/about%20fda/published/Benefit-Risk-Assessment-in-Drug-Regulatory-Decision-Making.pdf
3. European Medicines Agency (EMA). Benefit-Risk Methodology Project Update – Work Package 5: Effects Table Pilot Phase I. https://www.ema.europa.eu/en/documents/report/benefit-risk-methodology-project-update-work-package-5-effects-table-pilot-phase-i_en.pdf
4. Angelis A, Kanavos P. "Multiple criteria decision analysis (MCDA) for evaluating new medicines in health technology assessment and beyond: the advance value framework." Social Science & Medicine. 2017;188:137–156. https://www.sciencedirect.com/science/article/pii/S0277953617303933
5. Wouters OJ, McKee M, Luyten J. "Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009–2018." JAMA. 2020;323(9):844–853. https://jamanetwork.com/journals/jama/fullarticle/2762311
