Chapter 12 240 From an ethical perspective, efforts are needed to balance the collection of meaningful expanded access data against burdens imposed on patients and physicians in clinical care, especially to mitigate the possibility of physicians choosing not to offer expanded access out of fear of unsustainable effort. Over time, technological advances, such as those supporting learning health systems, should help diminish the need for manual data entry. In fact, as pragmatic randomized trials rise in prominence, they will offer the ability to include more generalizable populations and real-world settings in research, reducing some of the need for expanded access while offering many of the benefits of expanded access data and addressing some of its drawbacks. However, compared to expanded access, pragmatic trials are more costly and time-intensive and, like other trials, will remain unavailable to some patients based on factors including location and timing. Thus, expanded access still has an important role to play– and potentially important data to offer. What about transparency? Given that expanded access is distinct from traditional research, it may fall outside current requirements to publicly report results, reducing transparency and the ability to learn from these data, while facilitating biased reporting of only positive outcomes. Although companies are required by law to post expanded access policies online and indicate whether expanded access is available when posting trials to ClinicalTrials.gov, expanded access use itself is not considered an applicable trial for registration or results reporting.64 This makes sense in the context of clinical care, but when expanded access data are collected for research, research transparency requirements should apply. Posting expanded access research results will provide insight into whether and how expanded access benefits patients, information that is especially relevant to decisions about what resources should be devoted to this pathway. To address these concerns, FDA should issue guidance on reporting, data quality, and plans for enforcement, with broader clarity around the role of expanded access research within regulatory RWE frameworks, including when it is and is not appropriate. What role for IRBs? The role of IRBs will need to adjust as expanded access data are increasingly used for research. IRBs exist to protect research participants given conflicts that arise when their care is dictated by a research protocol rather than individualized clinical judgment. Expanded access has fit uneasily in this context, as clinical judgment is precisely what dictates treatment with an investigational agent outside a trial. Thus, IRBs reviewing expanded access (as required by regulation) historically have focused on confirming that potential individual benefits are likely to outweigh risks and that adequate consent is obtained. In fact, they may hesitate at the prospect of data collection that moves expanded access further from clinical care.
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