Outrage of the Month: A Disturbing Informed Consent Failure in Alzheimer’s Disease Trials
Health Letter, January 2025
By Robert Steinbrook, M.D.
Director, Public Citizen's Health Research Group
If you’re not outraged,
you’re not paying attention!
Read what Public Citizen has to say about the biggest blunders and outrageous offenses in the world of public health, published monthly in Health Letter.
(A version of this article appeared in the January 2025 issue of Worst Pills, Best Pills News).
In October 2024 a New York Times investigative report revealed that during clinical trials of two recently approved drugs for Alzheimer’s disease, participants were not told whether their genetic profiles increased their risks of brain injuries. According to the article, in trials of lecanemab (LEQEMBI) and donanemab (KISUNLA), “volunteers first had to sign consent forms that said people with certain genetic profiles faced higher risks of brain injuries from receiving the drugs, and that participants would be tested for them — but not told the results.”
The Food and Drug Administration (FDA) approved lecanemab in 2023 and donanemab in 2024. Public Citizen’s Health Research Group opposed the approval of both lecanemab and donanemab because their modest clinical benefits in temporarily slowing the rate of cognitive decline in patients with Alzheimer’s disease do not outweigh their substantial safety risks. Neither drug reverses the brain damage from Alzheimer’s disease; they may slow the rate of cognitive decline for a period, which is usually measured in months.
Both medications carry boxed warnings that monoclonal antibodies (including lecanemab and donanemab) directed against aggregated forms of beta-amyloid can cause amyloid-related imaging abnormalities (ARIA). ARIA are associated with brain swelling and brain bleeding and are more common in people with the genetic profiles that were tested for in the trials. The serious adverse events associated with this class of Alzheimer’s disease drugs include serious intracerebral hemorrhage (bleeding), some cases of which have been fatal.
After the Times article was published, Public Citizen’s Health Research Group called for a federal investigation of the two trials and the actions of the institutional review boards that approved the secrecy provisions. In December 2024 we formally requested that the FDA conduct this investigation. Under federal regulations, a fundamental protection for subjects is the requirement to obtain informed consent before involving individuals in research. If subjects had known that they were at higher risk of brain injuries, they might have decided not to participate in the trials. Because the results of genetic risk testing are information potential participants would want to know, the revelations about the secrecy provisions in the Alzheimer’s disease trials signify that the principle of informed consent was undermined.
As the Times article noted, “Drug trials are in part designed to illuminate risks, which is why volunteers are routinely informed of potential dangers before joining.” The informed consent failure in the Alzheimer’s disease trials is a wake-up call for clinical investigators and institutional review boards to exercise sound judgment and ensure that research subjects are fully informed about their risks.