Pedro Caetano
Executive Safety Physician, Debiopharm International SA, Lausanne, Switzerland
What if risk management began earlier? DRMPs serve as a framework for safety thinking in clinical development and support better benefit–risk decision-making.
In pharmacovigilance and drug safety, a structured risk management plan is often initiated in the later stages of a medicine’s life cycle – when products approach approval and formal risk management plans (RMPs) become mandatory. But what if structured risk thinking started much earlier during clinical development, when key decisions about patient safety are made?
This question has driven growing interest in development risk management plans (DRMPs): living documents designed to guide safety surveillance throughout clinical development. While currently it’s not a regulatory or legal obligation in most regions, DRMPs are increasingly recognised as good pharmacovigilance practice, as reflected in the Council for International Organizations of Medical Sciences (CIOMS) recommendations, particularly in complex therapeutic areas such as oncology.
An RMP aims to identify and characterise a product’s safety profile, define measures to minimise risks, and ensure that benefits outweigh risks once a medicine reaches the market. It is a regulatory document, overseen by regulatory authorities, and updated throughout the product life cycle.
The concept of a DRMP is rooted in the RMP; however, a DRMP applies these principles earlier in the process, encouraging safety teams to define, classify, and manage risks in a structured manner from the outset of clinical development. In this sense, it acts as a bridge between emerging clinical data and the more formal RMP that will later support marketing authorisation. It is also more flexible than an RMP, evolving with the programme and reflecting the level of knowledge available at each stage of clinical development. Their value lies in clearly articulating what is known, what remains uncertain, and how key risks are being managed.
This approach aligns with guidance from the CIOMS VII Working Group, which recommends that plans for detecting, assessing, understanding, reporting, and preventing adverse reactions should be initiated early and adapted as development progresses. In some regions, such as China, similar documents are required for clinical trials.
A DRMP is ideally initiated as soon as a molecule enters the clinical stage and regularly updated as clinical development progresses. Updates may occur at predefined milestones, for example, before a development safety update report (DSUR) or investigator brochure (IB) update, or whenever new safety information emerges that could affect the benefit–risk assessment. Update frequency should reflect the clinical development stage, complexity, and pace of new data generation.
The DRMP should always reflect the broader safety knowledge base, including the IB and DSUR, clinical study reports, and ongoing signal detection activities. As such, the DRMP acts as a “lighthouse” for the clinical development programme, ensuring consistent risk definitions and alignment across all key documents.
The document should present key risks, explain their mechanisms, and consider factors like target population, formulation, administration route, and clinical presentation. Risks should be classified according to their potential impact on the benefit–risk balance and continuously monitored, as they may evolve into identified risks as the data matures.
Descriptions of risk minimisation measures such as exclusion criteria, stopping rules, dose modifications, and toxicity management strategies are a key component of the document and are essential to ensure participants’ safety.
DRMPs may also capture programme-level safety data, such as product profile, adverse events of interest, safety oversight, and signal detection activities. Additional considerations may include compassionate use, product quality, and safety data exchange agreements.
As drug development progresses, the DRMP should support teams in the ongoing evaluation of emerging safety data, including adverse reaction frequency, severity, and the effectiveness of mitigation measures.
DRMPs provide a structured approach to managing risk during development. By centralising risk information in one place, they support alignment across development activities and clinical documents and facilitate a smoother transition to a robust and coherent RMP at the time of approval. They help to flag any assumptions and uncertainties regarding safety, thereby supporting decision-making and regulatory preparedness.
Beyond process, DRMPs also shape mindset by integrating structured risk thinking from the outset of drug development. They further enhance credibility with partners and stakeholders and help ensure that patient safety remains central as clinical programmes evolve.
For pharmacovigilance professionals, the message is clear: while risk is considered throughout drug development, a more structured and explicit approach to risk planning can add significant value. Adopting this approach during clinical development provides a practical means to strengthen safety strategies and, ultimately, to better protect patients.
Read more:
CIOMS Working Group IX, “Practical approaches to risk management of medicines”.
CIOMS Working Group VI, “Management of safety information from clinical trials”.
EMA, “Guideline on good pharmacovigilance practices (GVP), Module V: risk management systems”.
The Chinese National Medical Products Administration website.
Pedro Caetano
Executive Safety Physician, Debiopharm International SA, Lausanne, Switzerland
Laura Campora
Head of Clinical Safety, Debiopharm International SA, Lausanne, Switzerland
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