Chapter 12 238 With a variety of international analogues, expanded access allows patients to be treated with investigational medical interventions when approved options are inadequate and trial participation is unavailable.1 Developed through AIDS patient advocacy, expanded access has always existed at the blurry intersection of clinical care and research. The pathway is governed by US Food and Drug Administration (FDA) research regulations for investigational new drugs and devices. Yet, unlike research, which aims to advance generalizable knowledge and offers only incidental benefit (if any) to study participants, the primary goal of expanded access, like all clinical care, is to benefit participating patients. Recent trends have further blurred the lines around expanded access. There have been increasing global efforts to gather data from expanded access patients to support regulatory approval and coverage decisions, part of growing attention to real world evidence (RWE). Regulators have shown primary interest in expanded access safety data, but interest in efficacy data is also on the rise. From 1995-2018, the FDA accepted efficacy data from expanded access uses for 25 unique drug-indication combinations and the European Medicines Agency did so for 24, with frequency increasing in recent years;33 further analysis shows these numbers have doubled. Meanwhile, the United Kingdom appraised data from expanded access programs in 20% of its coverage decisions in the decade from 2010-2020.60 The FDA has also expressed greater acceptance of expanded access data to enhance generalizability in clinical development and sometimes suggests collecting expanded access data to support label expansions.60 The FDA will occasionally grant approval based on efficacy data solely from an expanded access program, as it did, for example, with alpelisib’s 2022 accelerated approval to treat overgrowth disorders.61 In addition, patient advocates have successfully secured federal funding to support research use of EA data, specifically in the context of amyotrophic lateral sclerosis,62 with the possibility of other disease areas to follow. If companies, regulators, and payers are going to rely on – and sometimes solicit – these data, they must address a variety of ethical considerations relevant to the future of expanded access, including issues related to data quality, payment, transparency, and institutional review board (IRB) oversight, among others. How useful is expanded access data? There are several upsides to collecting data from expanded access patients. These data can provide insight regarding patient groups beyond those eligible for trials, such as those who are older, younger, or sicker. For rare diseases, it may not be possible to include every patient in a trial, but it is nonetheless important, given small numbers, to learn as much as possible from every patient. Given the provision of expanded access in real world settings, expanded access
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