Harm reduction in paediatric off-label therapy

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

Best interests · Cystic fibrosis · Cystic fibrosis transmembrane conductance regulator · Disease · Do no harm · Genetic testing · Harm · Newborn screening · Cystic Fibrosis Research Advances · Ethics and Legal Issues in Pediatric Healthcare · Pharmaceutical studies and practices