Faculty Bibliography

Patient access to experimental drugs outside of clinical trials is called compassionate use or expanded access. Compassionate use/expanded access presents a powerful ethical dilemma in that it involves competing claims that both have moral weight: specifically, an individual patient's very understandable desire to try to extend his or her life versus the orderly and efficient functioning of a drug development and clinical trial system that benefits much larger numbers of patients. Patient advocates, the FDA, pharmaceutical trade groups, and state and national legislators in the US are all currently weighing in on patient access to experimental drugs, and new guidelines and rules are being introduced. In this editorial, we discuss the impulse to rescue individual patients facing dire diseases and underscore the ethical questions that such rescue efforts raise.

The first individualized therapy was administered in the United States just 2 years ago, when milasen, a therapeutic adapted from a Food and Drug Administration (FDA)-approved antisense oligonucleotide technology, was developed for a young girl with an extremely rare genetic mutation associated with Batten disease. Since then there has been an explosion of enthusiasm in developing customized treatments for extremely rare genetic conditions. These interventions raise some of the ethics concerns characteristic of novel therapeutics while simultaneously challenging existing legal, regulatory, and ethical understandings. Their individualized aspect blurs to the point of erasing the historically distinct line separating research from treatment, leading regulators and ethics oversight bodies to reevaluate existing policies. As experimental therapeutics, they raise the potential for both compromised informed consent and conflicts of interest, and their considerable expense provokes serious justice concerns. This article examines these challenges, urges multidisciplinary stakeholder engagement to address them in a transparent and practicable manner, and recommends initial policy responses.

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask "where's our Operation Warp Speed?" and "why isn't Emergency Use Authorization an option for our health crises?" Although this pandemic bears a number of unique features, the response to COVID-19 offers translatable lessons, in both its successes and failures, for non-pandemic diseases. These include the importance of collaborating across sectors, supporting the highest-priority research efforts, adopting rigorous and innovative trial designs, and sharing reliable information quickly. In addition, the regulatory response to the pandemic demonstrates that lowering standards for marketing authorization can result in increased safety concerns, missed opportunities for research and treatment, and delays in determining what works. Accordingly, policymakers and patient advocates seeking to build on the COVID-19 experience for non-pandemic diseases with unmet treatment needs should focus their efforts on promoting robust and efficient research designs, improving access to clinical trials, and facilitating use of the Food and Drug Administration's existing Expanded Access pathway.

Deciding whether to grant an expanded access request for a child whose sibling is enrolled in a gene therapy trial involves a number of complex factors: considering the best interests of the child, the psychosocial and economic impact on the family, and the concerns and obligations of researchers. Despite the challenges in coming to a substantively fair outcome in cases of discordant eligibility, creating a procedurally fair decision-making process to adjudicate requests is essential.

This article examines the origins and context of mandatory bicycle helmet laws in the United States. Localities began to enact such laws in the early 1990s, having experimented with helmet laws for motorcycles previously. As cycling became increasingly popular in the 1970s and 1980s because of a variety of historical trends, from improved cycle technology to growing environmental consciousness, cycling-related injuries also increased. Bicycle safety advocates and researchers alike were particularly troubled by head injuries. National injury surveillance systems and a growing body of medical literature on bicycle-related injuries motivated a number of physicians, cyclists, children, and other community members to advocate helmet laws, which they argued would save lives. Controversy over these laws, particularly over whether they should apply universally or only to children, raised public health ethics concerns that persist in contemporary debates over bicycle helmet policies. (Am J Public Health. 2020;110:1198-1204. doi: 10.2105/AJPH.2020.305718).