Table 2 Ethical considerations for selecting among eligible patients in high-demand gene therapy (GT) trials.
From: Ethical challenges for a new generation of early-phase pediatric gene therapy trials
Ethical consideration | Potential implementation | Illustrative example(s) |
Enhance scientific and social value | Increase representativeness to improve generalizability | • Prioritize eligible patients whose inclusion would improve the representation of relevant genotypes (e.g., variants) or other characteristics (e.g., sex, race, age, comorbidities) |
Increase knowledge about clinically relevant subgroups | • Prioritize—and potentially overrepresent—eligible patients with clinically relevant genotypes (e.g., variants) or other characteristics (e.g., sex, race, age, comorbidities) • Prioritize—and potentially overrepresent—eligible patients in whom the potential effects of the GT are more likely to be observable | |
Enhance risk–benefit profile for individual participants | Enhance potential benefits | • For neurodegenerative or similar diseases, prioritize eligible patients with earlier-stage disease if GT has the potential to halt disease progression, but not to restore affected tissues |
Reduce risks | • Prioritize eligible patients expected to better tolerate side effects or complications of GT • Prioritize eligible patients with advanced disease who would lose less quality of life or fewer life-years from adverse events • Prioritize eligible patients with reliable local health care and ability to maintain follow-up for GT safety | |
Promote justice | Provide equal chances | • Give all eligible participants an equal chance of participating in the trial |
Promote equal access | • Ensure that eligible patients with unreliable local health-care access (e.g., because of country of residence or lack of health-care insurance) receive an equal opportunity to participate | |
Prioritize disadvantaged groups | • Prioritize eligible patients with the most limited treatment or research options • Prioritize eligible patients from otherwise disadvantaged groups | |
Promote reciprocity | • Prioritize eligible patients who participated in preparatory research for the GT trial (e.g., natural history study) |
