Welcome to Ethics Consult -- an opportunity to discuss, debate (respectfully), and learn together. We select an ethical dilemma in patient care, you vote, and then we present an expert's judgment.
Last week, you voted on testing an Alzheimer's drug in Down syndrome patients. Here are the results:
Is it ethical to include people with Down syndrome in Alzheimer's drug trials?
Yes: 80.06%
No: 19.94%
Would it be ethical to use an Alzheimer's drug in Down syndrome patients if it hasn't been tested in that population?
Yes: 55.03%
No: 44.97%
And now, bioethicist Jacob M. Appel, MD, JD, weighs in:
It is essential to begin this discussion by noting that patients with Down syndrome are extremely diverse and that all of them have the same fundamental rights and deserve the same protections as any other potential human research subject. Individuals with Down syndrome should not categorically be refused the opportunity to participate in clinical research, nor should they be denied the benefits of that research. In fact, pharmaceutical companies should be encouraged to produce medications for groups of patients who cannot advocate effectively for themselves.
At the same time, ethical research must ensure that vulnerable populations are not taken advantage of or used as human "guinea pigs," as has occurred many times in this nation's past. Among the most notable of these disturbing experiments was the research of Saul Krugman, MD, and Robert W. McCollum, MD, at New York's Willowbrook State School in the 1950s and 1960s, which involved intentionally infecting intellectually disabled children with hepatitis. (After their work was published, Krugman became president of the American Pediatric Society and McCollum was appointed dean of the Dartmouth Medical School.)
It is not clear to me that all Down syndrome subjects lack the decisional capacity to consent to participate in Alzheimer's disease studies. If some people with Down syndrome have the cognitive abilities to consent meaningfully, they should be included like any other potential subject. However, the scenario seems to be asking whether individuals with Down syndrome whose intellectual disability is severe enough to lack decisional capacity regarding Alzheimer's disease research should still be permitted to participate in such investigations.
It is important to note that ethical research studies, by definition, are defined by equipoise: Researchers do not know whether the experimental drug works, so they are exposing the subjects to some (possibly significant) risk with unclear benefit. Under these circumstances, the first trials to determine safety and efficacy should be conducted on patients with capacity who can appreciate the risks of participation. If these initial trials are successful and therapeutic benefit is established with tolerable risk, then it would be acceptable to test the same drugs specifically on Down syndrome subjects lacking capacity (with the consent of their guardians or healthcare decision-makers) in order to establish efficacy in those patients with their specific etiology and genetic variant.
The downside of this approach is the downside of all pharmacological research on serious or potentially fatal illnesses. If dementia and/or death is considered the worst possible outcome, then equipoise cannot really exist because any other potential effect of the drug is preferable. In some cases, such as with multiple prospective experimental agents, there is an opportunity cost. In others, such as this scenario, there is the possibility that the experimental agent might backfire and accelerate dementia or death. In theory, that is a gamble that many patients confronting Alzheimer's disease, but not all, might accept. The harder question would arise if survey data showed that all or nearly all patients facing Alzheimer's disease or another dreaded illness would accept a particular risk for the hope of cure. If so, one might ask whether society would truly be acting justly or be doing individuals with Down syndrome a disservice by denying them an opportunity to make the same gamble solely on account of their intellectual disabilities.
Jacob M. Appel, MD, JD, is director of ethics education in psychiatry and a member of the institutional review board at Icahn School of Medicine at Mount Sinai in New York City. He holds an MD from Columbia University, a JD from Harvard Law School, and a bioethics MA from Albany Medical College. Appel is the author of the recent book, .
And check out some of our past Ethics Consult cases: Let Elderly Woman Visit Husband With COVID? MD/JD Bangs Gavel; Surprise Finding in Organ Donation Match Test; Compel Woman to Have C-Section?