Does ideal therapy exist? Perhaps “…curative in a single dose, this concoction could be mixed with a spoonful of chocolate syrup, and—of course—not cause any side effects….” Perhaps the real art of medicine involves helping patients with the reality of non-ideal therapy.
Dr. Eric B. Larson, in a state-of-the-art essay, discusses ethical issues in presenting current [2025] Alzheimer’s therapy to patients, given the uncertainties of discernible good effects. He does not use words like dilemma or false hope, but states that there is an “…absence of clinical or ethical consensus about what constitutes meaningful clinical improvement, outcomes, or risk factor modification…”
It seems like essential reading. Larson is internationally known for his seminal work in studying Alzheimer’s Dementia (AD) over three decades.
Just to oversimplify, will the kid with an “A” on a test have a significantly better life than one with a “D”? After the last blog piece showing lecanemab and donanemab results curves, a friend (lead editor of a current medical textbook and author of >200 peer reviewed cancer publications) wrote to me: “I’m still not sure that a difference of [~] 1 in the CDR-SB is clinically meaningful. ” [his italics]
“Good ethics starts with good facts,” is the pithy way bioethicist Dr. Norm Fost had of introducing complex clinical situations to us neophytes. Arcane concepts aside (and keeping it secular) practitioners usually use clinical medical ethics, a branch of philosophy, when interacting with patients.
Humans die. Go fact-check that assertion. Since this typist can’t verify the qualia of death in a personal way, some might call death assertions “fake news.” However, this typist has observed the actual moment of human death, as oncologists do. That might be knowledge from personal perception. So it goes for defining “fact” in the epistemology branch of philosophy.
Agreeing on facts seems more difficult lately. Medical research is about practical epistemology: how do we know what we think we know, and what does that mean for a patient?
Since the facts about AD therapeutic efficacy are, well, different than the facts for cancer therapy efficacy (like death rate), questions about measuring significant positive changes in patients’ lives are reasonable. Larson asks those questions, and cites other AD researchers trying to approach the problem.
Larson writes: “…There is no gold-standard method to define or calculate minimal clinically important differences…That an FDA expert committee convened to review a highly publicized anti-amyloid monoclonal drug recommended non-approval due to lack of compelling evidence of a treatment effect—a recommendation the FDA did not accept—reflects the lack of consensus on a threshold for a clinically meaningful benefit…In the absence of consensus on what constitutes a clinically important difference, the field uses not only psychometric outcomes but surrogate endpoints like brain amyloid…”
Back to ethical issues, the “four pillars” of medical ethics are usually taught as beneficence, non-malfeasance, autonomy and justice (or: doing good for the patient; not hurting them physically, mentally or financially; letting them make their own decisions; and letting folks have care equitably).
Clinical encounters assume beneficence, and Larson discusses how the risk/benefit ratio of the newer medications is a bit vague at this point in time; he implies the difficulty in explaining the current data to a patient. Protecting patients from malfeasance may be a bit harder. He does not even mention the context of drug advertising direct to consumers that exists.
There may be an autonomy issue in asking a person with cognitive issues, even subjective, for informed consent to proceed with therapy. The fourth ethical pillar is justice, usually taken to mean non-discriminatory access to care, but is also used to discuss cost issues in societies. Larson does explore current costs and implications for distributive access.
He states: “An alternative [to using new agents with uncertain clinical significance] would be to focus on elements that promote both general health and well-being and, especially, those that reduce risk of dementia and decline.”
The “US POINTER Study” , which uses lifestyle approaches to promote general health and might also prevent dementia, was published this year, while the Lancet Commission review 2024 on dementia also discusses lifestyle approaches.
The FDA does have a role in protecting the public from inadequate or even harmful medications, despite pharma’s good intentions. The salient example was thalidomide; a more recent example was the withdrawal of approval for Avastin® in breast cancer, when significant benefit was not confirmed. It was controversial with patient groups. Thousands of breast cancer patients had received that drug with known side effects; studies showed no significant effect on overall survival.
One of the ways cancer studies have changed recently is that investigators are tabulating quality of life issues, not just duration of life, since some therapies may cause long-term side effects in survivors. One hears the unwelcome idea that some cancer agents may just “prolong death.” If anti-amyloid monoclonals substantially prolong life, will it be good quality life? If they could be considered palliative agents, would they meet patients’ desired endpoints?
Larson, EB, Should Slowing Senescence Be Regarded as a Legitimate Enterprise of Health Care? Am J Ethics, December 2025, Volume 27, Number 12: E834-840
https://journalofethics.ama-assn.org/article/should-slowing-senescence-be-regarded-legitimate-enterprise-health-care/2025-12
[underlined phrases are links to articles or webpages]