Our drug development process has produced many life-saving medications, but patients experiencing rare diseases and similar conditions often are left with limited options for treatment. For an approved treatment to be developed, research on a new candidate or existing drug must validate safety and efficacy based on contemporary research expectations. Randomized clinical trials are conducted for this purpose, but they are also costly, laborious, and time-consuming. For this reason, The 21st Century Cures Act mandates that the US Food and Drug Administration look for alternative methods for approving drugs, in particular exploring the uses of real-world data and evidence. Expanded access (“compassionate use”) is a pathway for the clinical treatment of patients using drugs that are not yet approved for prescribing in the United States. Using real-world evidence generated from expanded-access patients presents an opportunity to provide critical data on patient outcomes that can serve regulatory approval in conjunction with other observational datasets or clinical trials, and in limited circumstances may be the best data available for regulatory review. In doing so, we may also support and encourage patient-centered care and a personalized medicine approach to drug development.

Vermeulen et al. suggest a moral duty exists for physicians to inform patients of “relevant opportunities” for Expanded Access. Such a duty is likely both too broad, leading to important practical challenges, and too narrow, without further steps to promote patient access. However, physicians should be expected to be aware of the EA pathway, disclose it to eligible patients, and support the pursuit of EA options reasonably likely to help.

Drawing on ethical and legal frameworks in the Netherlands, the United States and France, we examine whether physicians are expected to inform patients about potentially relevant opportunities for expanded access to investigational drugs. While we found no definitive legal obligation, we argue that physicians have a moral obligation to discuss opportunities for expanded access with patients who have run out of treatment options to prevent inequality, to promote autonomy, and to achieve beneficence.

Expanded access (EA) provides a pathway for the clinical use of investigational products (drugs, biologics, and medical devices) for patients who are without satisfactory therapeutic options and for whom a clinical trial is not available. Academic medical centers (AMCs) are likely to encounter EA requests, but it is unknown what support is available at these institutions for physicians seeking EA for patients. Methods: A landscape assessment was conducted at AMCs, focused on those within the Clinical and Translational Science Awards (CTSA) consortium. Results: Forty-seven responses were evaluated including 42 CTSA hubs. The large majority (43 of 47 respondents) reported using single-patient EA, while 37 reported multi-patient industry sponsored EA and 37 reported multi-patient investigator-initiated EA. Only half reported central tracking of EA requests. Support was available at 89% of sites for single-patient EA but less often for multi-patient EA. Types of support varied and were focused largely on the initial submission to the FDA. Conclusion: Use of and support for EA is widespread at AMCs, with support focused on single-patient requests. Gaps in support are common for activities after initial submission, such as FDA reporting and data collection.

Retrospective case studies of initiatives supported by the National Institutes of Health’s Clinical and Translational Science Award (CTSA) hubs can be used to identify facilitators and barriers of translational science. This case study investigates how a CTSA Expanded Access program adapted to changing FDA guidance issued in 2020 to support clinicians’ treatment of COVID-19 patients in Michigan. We studied how this program changed throughout the pandemic to support physicians’ requests for remdesivir, convalescent plasma, and other uses of unapproved drugs and novel medical devices. A protocol for retrospective translational science case studies of health interventions developed by CTSA evaluators was used for this case study. Data collection methods included seven interviews and a review of institutional data, peer-reviewed publications, news stories, and other public records. The barriers identified include evolving guidance, misalignment of organizational operations, and the complexity of the research infrastructure. The facilitators of translation include collaboration between research and care teams, increasing engagement with a broad network of supporters, and ongoing professional development for research staff. The findings of this case study can be used to inform future investigations of the principles underlying the translational process.