Ethical Considerations for Clinical Research in Persons with a Terminal Illness.

Clinical research in persons with a terminal illness (PTI) can offer valuable scientific opportunities but raises the challenge of ensuring adequate protections for participants. Existing ethical frameworks provide limited, and sometimes conflicting guidance for navigating this tension. Given that enrolling only PTI (e.g., palliative care research) or PTI alongside participants without a terminal illness (many studies in geriatrics and other disciplines) is somewhat common, establishing the right balance is important. This paper-grounded in general research ethics requirements-thus proposes a framework based on the defining feature of PTI, namely, limited life expectancy. We explore how limited life expectancy and characteristics common (but not unique to) PTI (e.g., decisional impairment) can make it difficult for studies to meet one or more commonly recognized ethical requirements (e.g., social value, favorable risk-benefit ratio, fair participant selection, informed consent, and respect for participants and third parties). We suggest ways to address these challenges and offer considerations for IRBs when evaluating studies with adults with a terminal illness. This approach aims to balance protecting PTI and ensuring they can contribute to important research without undue restrictions.