Generating evidence from expanded access use of rare disease medicines: challenges and recommendations 227 11 ♠ INTRODUCTION An estimated 7000 rare diseases affect approximately 10% of the population1. Although the number of patients with a given rare disease is by definition limited, the collective impact of these diseases is substantial. Yet only about 1 in 42 patients with a rare disease had even a single United States (US) Food and Drug Administration (FDA)-approved treatment option.13 Before granting marketing authorization, regulatory agencies require evidence that the treatment benefits outweigh the risks, and generating such evidence requires time. Patients who have neither time nor approved treatments at their disposal and are unable to participate in trials, may seek access to investigational medicines via expanded access programs.1 Expanded access pathways allow patients with life-threatening or debilitating conditions to access unapproved medicines. Terminology for expanded access programs varies, as in English alone it is known as ‘named-patient use’, ‘single-patient IND’, ‘compassionate use’, or as ‘expanded’, ‘managed’, ‘early’ or ‘special’ access, all to denote non-trial access to unlicensed medicine.14 Historically, expanded access pathways were designed primarily to provide a treatment - to grant patients access to medicine outside of studies as last resort - although the collection of additional data was also contemplated.15 Over the years, there has been a shift to increasingly emphasize the role of expanded access data. Although the primary intent of expanded access remains providing treatment to patients, data generated through expanded access have been reported in a large number of peer-reviewed publications, submitted in regulatory filings to the FDA and the European Medicines Agency (EMA), and used in health technology assessments.11 However, opinions differ regarding to what extent data can be collected in the first place, and if so, how and when such data can be relied upon. In this perspective, we clarify issues of data collection and subsequent analysis during expanded access programs in the US and European Union (EU). We first discuss detailed examples from the usage of expanded access data relating to rare disease medicines. Subsequently, we highlight the discrepancies in regulatory views on expanded access, discuss related issues of access inequality, and finally discuss ethical considerations of data collection and analysis. Lastly, we suggest means for improving expanded access data collection and use, with a particular focus on the EMA. 1 https://rarediseases.org/
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