Including real-world data from expanded access programmes into regulatory approval decisions and health-economic analyses: benefits and 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 programs were not considered for research. Nowadays, these programs 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, we first aim to investigate how RWD from EA programs has been used in the past by regulators (e.g. Lutathera, developed at Erasmus MC). Secondly, we will investigate statistical techniques to appropriately combine RWD (‘big data’) and RCTs. Thirdly, we will assess whether RWD from EA can play a role in cost-effectiveness analyses. Lastly, we aim to quantify the value of RWD from EA in terms of value of information analyses.

The project has resulted in considerable new scientific insight in the value of expanded access, and there is now more understanding of the role of expanded access as a way to assess treatment efficacy and cost-effectiveness. We have shown that RWD from are already incorporated in decision making by regulators and reimbursement bodies. In addition, we have provided guidance on the collection and analysis of data of expanded access programs, and we have developed a novel statistical approach to combine the RWD from expanded access programs with data of a clinical trial. The PhD thesis and the 11 associated peer-reviewed publications that are the main deliverables from this project already represent a major contribution in this field. The research activities have also contributed to a tangible change in data collection practice: most clients of myTomorrows now collect RWD as part of their expanded access program. We believe that this is a success story.