Clinical trials for the Alzheimer's drugs lecanemab (Leqembi) and donanemab-azbt (Kisunla) are facing scrutiny following reports that participants were not fully informed about genetic risks associated with brain injuries. The New York Times revealed that volunteers in these trials signed consent forms acknowledging higher risks of brain injuries based on certain genetic profiles but were not told their individual results. This has sparked concerns about the integrity of informed consent and the ethical conduct of the trials.
Concerns Over Informed Consent
Dr. Robert Steinbrook, director of Public Citizen's Health Research Group, has called for investigations by the Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP) at the Department of Health and Human Services (DHHS). According to Dr. Steinbrook, "The requirement under federal regulations to obtain informed consent before involving individuals in research is a fundamental protection for research subjects... If subjects had known that they were at higher risk of brain injuries, they might have decided not to participate in the trials. This is information potential participants would want to know."
Modest Benefits and Substantial Risks
Both lecanemab and donanemab-azbt have demonstrated only modest clinical benefits in treating Alzheimer's disease. These benefits, critics argue, may not outweigh the substantial safety risks, including brain swelling and bleeding (amyloid-related imaging abnormalities or ARIA). The withholding of genetic risk information raises questions about whether participants could make fully informed decisions about participating in the trials, given these risks.
Call for Investigation
The FDA and OHRP are urged to formally investigate the conduct of the trials and the actions of the institutional review boards that approved the secrecy provisions. The focus of the investigation should be on whether the principle of informed consent was undermined and whether the potential risks were adequately disclosed to participants. The outcome of these investigations could have significant implications for the future conduct of clinical trials, particularly those involving vulnerable populations and potentially risky interventions.
