Tobias Polak

Expanded access as a source of real-world data: An overview of FDA and EMA approvals 95 5♦ conclusions. expanded access programs harbor inherent flaws – such as data quality issues - and first and foremost: the lack of randomization. Although this should always be kept in mind, it does not mean that the information from patients treated under expanded access should simply be ignored. On the contrary, various approvals rest on data from single-arm clinical trials.30 Although patients in expanded access programs are not eligible for clinical trials, this does not imply that their treatment data do not qualify for analysis. Data from every patient could provide useful insights and moreover, our study shows that the EMA has considered data from these patients critical in specific approvals. A paradoxical situation arises when individual member states do not allow RWD collection during expanded access programs, yet the EMA uses these RWD in decision making. Harmonization across regulators and individual member states should solve these paradoxes. We encountered differences in regulatory decisions. In seven cases, the FDA considered data ‘pivotal’ to the approval whereas the EMA had not approved the product (six cases), or the data were merely considered ‘supportive’ (one case). Conversely, the FDA has not (yet) approved two products whereas the EMA did. Despite international drug regulation harmonization efforts,31,32 there is still room for regulatory cooperation across the Atlantic. Considering our observations in a greater context it appears conventional lines between treatment and research are becoming blurred. This is true for both the field of RWD as a whole and for RWD from expanded access in particular. An example of the former are administrative data used for analyses: data that were not collected for the purpose of research are now found at the heart of an analysis. Similarly for the latter, where expanded access programs were traditionally also meant exclusively for treatment, data collection and thereby research has become a reality. The changing position of expanded access patients from treatment-subjects to (partly) researchsubjects, provides a challenge for bioethicists.11,12,33 When it comes to comparisons between RCTs and RWD: both have their merits. On the one hand, the control of variability and assurance of data quality in RCTs leads to valid results. On the other hand, these trials target specific homogenous patient populations, e.g., younger and with fewer comorbidities, which limits the generalizability of findings.26,27 RWD represents a more heterogenous or real-life population, conclusions drawn on RWD are arguably more applicable in day-to-day clinical settings.10,34 Finding the right balance between RWD and RCTs can become an interesting topic for (bio)-statisticians, (pharmaco)epidemiologists, regulators, and industry. Awareness of the potential value of RWD from expanded access should facilitate that these data are used appropriately. This helps pharmaceutical industry and regulators determine whether expanded access – and associated RWD – is useful. For patients, this would hopefully result in speedier access to more diverse treatments.

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