One of the most challenging aspects for sponsors is the ability to create comprehensive information from clinical trials for new drug applications that will meet the stringent requirements of the Food & Drug Administration (FDA) and the European Medicines Agency (EMA).
Integrated Summaries of Safety and Efficacy are not only required by these agencies but are some of the most important documents for submissions and subsequent approvals. As critical as they are, Integrated Summaries can pose challenging timelines, data harmonization hurdles and possibly considerable costs.
There is no argument that this is a complicated and complex activity and a process to launch an Integrated Summaries project should be considered as early as possible. For sponsors looking to initiate Integrated Summary projects and outsource the task to a CRO, they should expect detail on five essential pillars to ensure success:
Initiation includes establishing a clear, concise package that is correctly transferred to the CRO team. A project charter that establishes the scope and objective of the project should be developed and agreed upon and that includes such activities as identifying studies, parameters and key data. Definition of the stakeholders and the decision-making process is essential as well as estimates of time for review and possible constraints that may impact the timing. Schedules and budgets are part of this process as well as developing overall and immediate milestones, measurements and reporting.
Planning creates the roadmap and, because of its complexity is likely one of the most important foundations of the process as it will establish a detailed path forward. The project plan should include a gap analysis between incoming data sources and expected output. It includes planning and management of the schedule, defining the assumptions and constraints, what documentation is available for all studies and how that data is structured. It should include a determination of which activities can be undertaken in parallel and which are sequential, how to batch the studies and an estimate of activity duration, and what resources need to be deployed.
As part of the planning process, allocation of resources/team members need to be determined, including timelines and time zone advantages should the trials be conducted in multiple locations. Work groups, led by specified project leaders, should be defined that align skill sets for maximum productivity. Contingency staffing plans also need to be considered.
Quality is also part of the planning process. Documentation of how the product deliverables will adhere to defined quality standards includes double programming for all analysis data sets, full validation for all unique tables and spot checks for some repeated tables and listings.
Budget is a significant factor that includes estimations of hours and resources as well as an anticipation of budget changes that may require defined approval processes.
And, underpinning all these activities are concise communications and risk plans that assure meeting frequency, expectations for response times and escalation pathways, and resource availability in case of delays.
Execution is just that and will be more successful with a thorough project plan, particularly when established quality standards and operational definitions are faithfully implemented during project execution and validated processes are not altered to shorten timelines.
Monitoring is required to assure compliance with the project plan. Issue logs for detailed discussion of specific issues and resolutions are essential as well as tracking the status of each individual deliverable with specific details on the status of programming and validation.
The final step is successful closure of the project that includes a complete wrap-up of all activities, including contractual obligations, capturing and delivering all artifacts, planning for next steps of supporting the regulatory review. As part of this process, it’s also helpful to spend some time in evaluating ‘lessons learned’ that will identify challenges/issues that can be mitigated or completely avoided in future work.
To support the complexities and flexibility necessary to successfully implement an Integrated Summaries project, an experienced CRO is invaluable. The CRO team serves as an active partner to ensure a timely and high quality integrated summary.