Results from expanded access programs: a review of academic literature 127 7♦ INTRODUCTION Patients who cannot be adequately treated with marketed therapies and who simultaneously are unable or ineligible to enroll in clinical trials may seek different means of accessing unlicensed treatments. Legislators have created ‘expanded access’ pathways to allow these patients to access unregistered medicines.64 The United States (US) Food and Drug Administration (FDA) institutionalized ‘expanded access’ in 1987 in efforts to provide more treatment options for AIDS patients.4 The European Medicines Agency (EMA) has drafted Guidance on Compassionate Use in 2007, but individual members states of the European Union (EU) have a longer history of individually regulating national ‘expanded access pathways’ and still retain that freedom today.65 The primary intent of expanded access programs is to provide treatment access, which contrasts with the primary intent of research in clinical trials. Nonetheless, there is an increasing interest in simultaneously providing access whilst collecting, analyzing, and disseminating results from expanded access usage. First, these data may further estimate treatment patterns and outcomes in non-trial (e.g., ‘real-world’) patients.51,52 Second, including expanded access may increase statistical precision simply by increasing patient numbers - this pertains particularly to expanded access use of rare diseases drugs.11,66 While various regulators in the EU and US mandate some form data collection during expanded access, others restrict or even prohibit the collection and subsequent analysis.66 To date, opinions differ to which extent data collection under expanded access is feasible, desirable, and reliable. The evidence that stems from expanded access has been used to inform safety and efficacy labels by regulatory bodies such as the FDA and EMA.50 Furthermore, data from expanded access are incorporated by health technology assessment bodies to determine cost-effectiveness of novel therapies in the United Kingdom, the Netherlands, the United States, and France.67 To what degree data from expanded access of investigational medicine are published in academic literature remains unknown. A mapping of expanded access scholarship with regards to time, location, subject, research methodology, and authorship is lacking. There is no information on which drugs are used in expanded access literature, by how many patients, for which diseases, and where such expanded access programs take place. Here, we examine to which extent research on expanded access is disseminated in the academic literature. Furthermore, we analyze the type, subject, and participants within such research. We identify disparities in scientific research across geographies and disease areas and discuss the resultant issue of access inequality. Lastly, we provide recommendations on the harmonization of expanded access research in the future and facilitate such research by the data set created in this work.
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