The ethics of expanded access research 239 12 ♠ data can provide information about factors like adherence that are harder to obtain in strictly controlled trials. Compared to other sources of RWE, such as claims databases or social media, EA is more structured, prospective, and reliable. In addition, when uncertainty remains about interventions that may help address a public health emergency like COVID-19, expanded access can facilitate access with greater data collection than alternative approaches such as emergency use authorization or early grants of traditional marketing approval. Finally, gathering data from expanded access patients allows them to altruistically contribute to scientific knowledge. These factors suggest ethical reasons to pursue expanded access data.60 However, there are also serious limitations, particularly when compared to traditional research. Most importantly, expanded access occurs in an unblinded, nonrandomized setting allowing only observational measures that may be rife with bias. Moreover, data collection is not governed by the same quality standards as clinical trials. Patient selection is an additional concern, as privilege likely influences which patients obtain expanded access (based on clinician knowledge and institutional support), replicating challenges seen across the health care system and limiting the ability of expanded access data to fill diversity gaps in clinical trials. These considerations make it ethically imperative not to overstate the value of expanded access data. Who bears the burden and cost? Although companies are allowed to charge the direct costs of drugs provided via expanded access, well-resourced companies usually provide unapproved drugs for free. The ability to collect meaningful data may incentivize smaller companies that might otherwise decline expanded access to also provide access, to the potential benefit of patients. However, it is important to acknowledge that collecting expanded access data beyond minimum regulatory and clinically relevant requirements will be more resource-intensive for clinicians. Anecdotally,physicians alreadydescribe lack of compliance with regulations for submitting adverse events and summary reports for expanded access, let alone providing additional information to companies. Even at well-resourced institutions, clinicians may find this burdensome absent substantial additional support.63 Although companies already incur costs in offering expanded access, to the extent data collection will benefit their regulatory and reimbursement prospects, they should financially support additional physician effort. Alternatively, since government payers also fund research and companies without any marketed products may be under-resourced, it may be appropriate to use grant funds to secure expanded access data in exceptional cases, especially rare diseases.62
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