In a world where many operational and strategic clinical trial activities are outsourced to Contract Research Organizations (CROs), the design and content of the Safety Management Plan (SMP) will greatly influence the execution of clinical trial drug safety activities.
The SMP is a key document delineating the respective roles, responsibilities, processes and timelines for safety activities allocated between the Sponsor and the CRO(s). This is a practical and operational document, not to be confounded with the Development Risk Management Plan (dRMP) or Safety Monitoring Plan or Activities, more focused on the strategy for detecting and mitigating any change in the risks for patients.
Here are some principles to consider when preparing a SMP with a clinical research service provider.
Define your expectations upfront
The Sponsor should define precisely what items should be covered in the SMP, and design upfront an ideal SMP template, driven by a corresponding SOP. Bear in mind that each vendor has a different style for writing SMPs; without an attempt to harmonize the format and content of such documents, processing safety data with multiple vendors on multiple trials can quickly become a significant and unnecessary challenge. There are also many activities and steps taking place during a trial, all of which should have an owner and a timeline. The SMP should represent a checklist of all the Sponsor has identified as key safety activities. Take this challenge: how many separate activities related to clinical trial safety (operational or more strategic) can you identify? You should get at list of 30 or more. Now check with your existing SMPs. How many gaps do you have?
Make it clear
The SMP will be the reference document for operational activities, adding to or replacing some sections of the Sponsor’s or Vendor’s specific SOPs. The training of the Clinical Research Associates (CRAs), Medical Monitor and Safety Teams will derive from its content. Roles, responsibilities, activities and timelines should be perfectly clear and understandable. Avoid SMPs which look like a writing style exercise, and instead opt for a model with tabulations and flowcharts. The SMP is a reference document, accessing its content to check a specific point should be easy and direct. Lack of clarity always results in lack of compliance.
It is OK to be obsessional
Getting to the nuts and bolts of the operations is a must and covering all situations is critical. For example, have you included a process for reporting SAEs when the EDC is down? Who checks the MedDRA coding? Who stores the worldwide regulatory submission compliance? Is there a process and timelines for management of deviations? Have you referenced all applicable regulations and SOPs? Did you include Serious Breach and Urgent Safety Measures reporting? Did you define who is part of the unblinding team for reporting purposes? This is why a detailed SMP template with a robust checklist becomes invaluable and will help reduce bumps down the road.
It is only one part of a greater ensemble
The SMP is an operational plan that will drive the execution of the safety related activities during a trial. It is part of a broader ensemble of activities and strategies which, together, ensure that Sponsor and Vendors are meeting their commitments to compliance and patient safety: Development Labeling, Development Risk Management Plan and Signal Management Activities, Drug Safety Monitoring Board, Investigator Brochure Maintenance, Safety Governance Model, and many others. By simplifying the apparent complexity of operational Clinical Trial safety activities through logical, clear and comprehensive SMPs across all your programs, you will reduce the risk of process deviations and make everyone’s life easier.
A well designed and comprehensive SMP will reduce compliance gaps and increase operational efficiency. Most importantly, it will also foster a better use of your expertise, brain power and resources for more strategic and critical benefit-risk management activities, serving your commitment to patient safety.
JP Clement, MD