Impact of indication changes on scoping for European Union Joint Clinical Assessment: scale of the problem and how to address it.

Objectives: The European Union Joint Clinical Assessment (JCA) process aligns with the regulatory process to promote faster patient access. The PICO (population, intervention, comparator, and outcome) scoping for the JCA must occur before the regulatory process concludes. The risk of indication change during this period is one of the concerns for the success of the JCA process. We investigated the frequency and type of changes that are made to proposed indications and examined how such changes could impact the PICO scoping for JCA.

Methods: Twenty-seven recently approved oncology and 15 Advanced Therapy Medicinal Products (ATMP) products were included. Observed indication changes were categorized into editorial or population changes population changes were graded based on the anticipated impact on JCA scope depending on their nature.

Results: The majority of products had only editorial changes between proposed and approved indications (67 percent). Once amended, it was common for the indicated population to be narrowed, and rare for it to be broadened. The most common change observed was the shift to a later treatment line. The greatest risk for PICO rescoping would be when new populations would have been added, or new subpopulations or subgroups would have been omitted from the initial scope.

Conclusion: The impact on JCA scope depends on the proposed indication wording and how the PICO scoping would have been conducted. Rescoping warrants a considered decision, and to mitigate the risk of delays, dialogue between the assessors and the developer is recommended for informed decision-making.