Real-world data from expanded access programmes: statistical and political challenges

Patients suffering from seriously debilitating or life-threatening conditions who are not eligible for further treatments or any clinical trials, may resort to ‘expanded access’ (EA): pre-approval access to investigational treatments. EA is an option for a select group of drugs that passed Phase-I/II, but have not yet obtained full regulatory approval. The growing number of requests for EA and recent movements, such as Right-to-Try in the US, stress the interest of patients and physicians in EA.  

Historically, EA programmes were not considered for research. Nowadays, these programmes often incorporate basic effectiveness and safety data collection. Such data – collected outside of conventional clinical trials – is called ‘real-world data’. Although the interest in RWD has risen over the last years, little is known about how, why and whether real-world data (RWD) and expanded access (EA) can be combined.  

To answer the above, the first aim is to investigate how RWD from EA programmes has been used in the past by regulators (e.g. Lutathera, developed at Erasmus MC). Secondly, statistical techniques will be investigated to appropriately combine RWD (‘big data’) and RCTs. Thirdly, there will be assessed whether RWD from EA can play a role in cost-effectiveness analyses. Lastly, the aim is to quantify the value of RWD from EA in terms of value of information analyses.  

This research will help clarify the usability of these data. Awareness of the potential value of RWD from EA should facilitate that these data are incorporated in decision making whenever this is feasible and appropriate, and this should impact on traditional clinical development. For patients, this better use of available data can result in speedier access to more diverse treatments.