How To Keep High-Risk Studies Ethical: Classifying Candidate Solutions

Abstract

Early-phase HIV cure and remission trials frequently present an unfavorable benefit:risk ratio for participants who are already clinically stable on antiretroviral therapy. Resolving this ethical challenge involves evaluating candidate solutions across four primary domains: risk reduction, participant benefit enhancement, robust informed consent, and the consideration of social value. Risks can be mitigated through stringent preclinical testing, dose modulation, enhanced monitoring safeguards, and the exclusion of vulnerable groups. Alternatively, net participant benefits can be optimized by recognizing non-standard clinical advantages, providing financial compensation, acknowledging the psychosocial value of altruism, or recruiting patient cohorts with limited therapeutic alternatives. Autonomous informed consent also provides a crucial ethical justification, challenging overly paternalistic constraints against individuals knowingly accepting medical risks. Finally, regulatory and philosophical frameworks can balance individual net risks against the profound potential benefits to non-participants and global public health. Systematically examining these four dimensions clarifies how high-risk, early-phase biomedical research may remain ethically defensible. – AI-generated abstract.