Rebecca Johnson Bista

Cystic fibrosis (CF) is a life-limiting genetic disease frequently associated with pancreatic insufficiency (PI), traditionally considered irreversible. CF transmembrane conductance regulator modulators such as elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta) have transformed CF care yet remain FDA-approved only for children aged 2 years and older. We present the case of a 9-month-old female with CF and PI whose mother, highly health-literate and resourceful, pursued early ETI exposure through breastmilk transfer and later direct off-label dosing, despite medical guidance and regulatory restrictions. Remarkably, the child achieved pancreatic sufficiency, discontinued pancreatic enzyme replacement therapy and showed no evidence of hepatic or ophthalmologic toxicity. This case raises significant ethical questions: What constitutes an appropriate physician’s response when parents pursue unapproved but plausibly effective therapies? Should monitoring and harm reduction be seen as ethically permissible, or should stronger discouragement—including refusal of guidance or child protective intervention—be considered? Using an adapted risk–benefit framework derived from complementary and complementary medicine ethics, we argue that the medical team’s approach—recommending standard of care while monitoring for safety and efficacy—was ethically justifiable harm reduction in light of the mother’s persistence, the plausible biological rationale and early positive outcomes. We further explore how this assessment may shift when FDA-approved alternatives become available and compare this case to analogous dilemmas such as paediatric stem cell tourism. Ultimately, we suggest that calibrated physician responses, scaled to the degree of risk and potential benefit, best serve the child’s interests in ethically ambiguous contexts of parental pursuit of unproven but potentially beneficial treatments.

Many research projects rely on human biological materials and some of these projects generate revenue. Recently, it has been argued that investigators have a moral claim to share in the revenue generated by these projects, whereas persons who provide the biological material have no such claim (Truog, Kesselheim, and Joffe 2012). In this paper, we critically analyze this view and offer a positive proposal for why tissue providers have a moral claim to benefit. Focusing on payment as a form of benefit, we argue that research is a joint project and propose a contribution principle for paying participants in those joint projects. We distinguish between contributions that shape a project’s revenue generating properties, grounding a claim to payment, and contributions that fail to ground such a claim. We conclude, contrary to existing arguments and practices, that some tissue providers have a moral claim to payment beyond compensation for risk and burden. This conclusion suggests that investigators, institutions, and sponsors should reconsider the fairness of their current practices.

The prevailing “segregated model” for understanding clinical research sharply separates it from clinical care and subjects it to extensive regulations and guidelines. This approach is based on the fact that clinical research relies on procedures and methods—research biopsies, blinding, randomization, fixed treatment protocols, placebos—that pose risks and burdens to participants in order to collect data that might benefit all patients. Reliance on these methods raises the potential for exploitation and unfairness, and thus points to the need for independent ethical review and more extensive informed consent. In contrast, it is widely assumed that clinical care does not raise these ethical concerns because it is designed to promote the best interests of individual patients. The segregation of clinical research from clinical care has been largely effective at protecting research participants. At the same time, this approach ignores the fact that several aspects of standard clinical care, such as clinician training and scheduling, also pose some risks and burdens to present patients for the benefit of all patients. We argue that recently proposed learning health care systems offer a way to address this concern, and better protect patients, by developing integrated review and consent procedures. Specifically, current approaches base the need for independent ethical review and more extensive informed consent on whether an activity is categorized as clinical research or clinical care. An ethically sounder approach, which could be incorporated into learning health care systems, would be to base the need for independent ethical review and more extensive informed consent on the extent to which an activity poses risks to present patients for the benefit of all patients.