While different than genetic signs for dementia, biomarker information found in research brain scans also can suggest heightened risk for developing Alzheimer’s disease, and thus the disclosure or withholding of results raises ethical questions for IRBs and investigators.
In particular, PET scans show levels of amyloid plaque accumulation within the brain, which may signal an increased risk of developing full-blown Alzheimer’s, particularly in patients who already have dementia symptoms. The clinical options and interventions are limited, and thus PET scans are not typically covered for reimbursement.
“[PET scan results] are not medically and clinically actionable in the traditional sense of that term,” says Jennifer Lingler, PhD, who studies ethical issues in dementia care and research as an associate professor of Health and Community Systems at the University of Pittsburgh. “But one of the things that makes this an interesting area of research is that these scans are being utilized with really increasing frequency in all sorts of studies of cognitive aging, from looking at normal, cognitively healthy older adults to people with all different forms of dementia. These scans are becoming a gold standard of sorts for identifying whether there is Alzheimer’s pathology in the brain.”
Thus, in research studies that include PET scans, investigators and IRBs must decide whether and how to present such information, for which there is little medical recourse but could be psychologically devastating to research subjects.
“If you see a tumor on a brain scan, you have a different set of obligations to a patient and possibly extending that communication to their clinical providers,” Lingler says. “If there is not a treatment that can be implemented, it really falls into more of a gray zone ethically. There is some uncertainty for investigators: ‘Do I have an obligation to even share this information with my participants, let alone ask them to consider relaying this back to their medical providers?’”
Lingler and colleagues designed a study1 to assess disclosure of amyloid scan results to people with mild cognitive impairment (MCI). They wanted to ensure comprehension of the scans and any subsequent results by developing educational materials for use in pre-test counseling and post-test disclosures. The research subjects had MCI, but were participating in a simulated script that modeled the experience of having a brain scan and being told the results. The participants received fictitious but realistic information regarding brain amyloid status, followed by an explanation of how results affect Alzheimer’s disease risk. The study and analysis supported the following recommendations:
- offer pre-test counseling,
- use clear graphics,
- review participants’ own brain images during disclosures,
- offer take-home materials, and
- call participants post-disclosure to address emerging questions.
Lingler and colleagues concluded that the research participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one’s amyloid status as valuable and empowering. Finding this approach promising, the researchers are now working on a study using actual brain scans and real results that may be shared with people with MCI. IRB Advisor asked Lingler to provide a few more details about this emerging line of research.
IRB: What are some of the basic implications of your research for IRBs and investigators?
Lingler: I think investigators that are considering releasing these results to research participants should offer pre-test counseling of some sort. They would have an obligation, as this point in time, because we don’t know what the psychological repercussions might be. There [needs to] be some follow-up monitoring and have safeguards in place for [recognizing] any adverse psychological outcomes, and a plan in place for addressing those. We would also have to, of course, recommend at this point in time that individuals be screened in advance for any mood instabilities, suicidal ideations, or things of that nature. We don’t want to be overly paternalistic, but investigators should take those things into account.
For IRBs, my suggestion would be to evaluate for the potential risk of the scan itself distinct from a set of risks of receiving the results. They need to add a second layer to this instead of just the traditional mindset of looking at the safety profile of things like the imaging agent or the PET scan itself. There is a second layer now associated with the risks of disclosing and withholding that information. So IRBs need to think about balancing a participant’s right to their own research data versus the psychological risks that [disclosing the data] might present.
IRB: So the pre- and post-counseling about the procedure and disclosure of results all fall under aspects of informed consent?
Lingler: Our current study is finding that the counseling session is longer and more detailed than the typical informed consent process. The informed consent process [typically] zeroes in on more consenting to the research study, and as part of this research a scan is going to be done. Really, people have to consent to the physical risk of the scan. The idea of whether they want to know the scan results is sort of a second layer, and we haven’t found it very efficient to try to roll all of that into informed consent. Even if we view informed consent as a process, a dialogue, an exchange, the type of counseling that we are suggesting, promoting, and using in our current study is more detailed and more of a separate issue for people to think about. Because we also would not want to exclude people from studies just because they don’t want these results back. There are plenty of studies where, for scientific purposes, they do these scans and there wouldn’t be any reason to limit those participants who, in fact, don’t want to have the results.
IRB: Just to clarify — regarding the simulated sessions in the published study, this was a scripted interaction with people with MCI that did not involve assessment or disclosure of the research participant’s actual medical data?
Lingler: Exactly. In the simulated sessions, we recruited people and told them we are trying to develop and refine patient education materials so we will know how well our [approach] works. We were looking for people to listen and view the information we were developing. In the simulation, we asked people to imagine that they had undergone a special type of brain scan. There was a script that was administered, and the individual also had a copy of the script in hand because they do have mild cognitive impairment. It was scripted and one of the main reasons for that was to ensure that, for research purposes, everyone is getting the exact same [message]. We wanted to evaluate how much they understood — and, obviously, that could be compromised if different people hear different things. We told them at the outset that this is the script you are going to hear, but the results were fictitious.
IRB: Even though there is little that can be done in terms of treatment, are you finding that participants still want to know their brain scan data and, to some degree, their Alzheimer’s risk? Does it allow them to make life decisions or have some clarity about their mental health?
Lingler: They need to think about whether this is information that they want to have. As we reported in the article and in our current study, whether we are doing simulations or doing the real thing, we have seen the gamut of every type of preference you can imagine. We’ve seen families that want the results but the patients don’t, and vice versa. People who don’t want the information versus people who do want the information. In our current study, because people have the opportunity to get these results, we are seeing a select population in a sense that is very information-seeking. We ask them at the time of study entry, before they undergo the pre-test counseling, “at this point in time, about how interested are you in receiving your results on a 1 to 10 scale?” And the average is over 9. People are highly interested, and the families are averaging between 8 and 9 in terms of their interest in getting the results. Most are participating in the study because they want the results. People are very interested and they know they can’t get this scan in clinical practice. There is not reimbursement for it by CMS.
But our job is to work with them and make sure they really understand the limitations of this and they don’t overestimate and equate a scan diagnosis with Alzheimer’s. They also understand that a negative scan does not mean they are never going to get dementia syndrome of any sort. So, the population we are working with has mild cognitive impairment. People with full-blown Alzheimer’s — if they have a positive scan, in a clinical context it’s not much of a game-changer. It’s just confirmatory at that point because they already have the disease.
Interesting and potentially valuable is this subset of people that we have been focused on with mild cognitive impairment. We know they are exhibiting cognitive changes and they are at high risk for developing Alzheimer’s disease. In this population, the amyloid plaque scan can really help to distinguish those whose syndrome of MCI is likely to represent an ensuing Alzheimer’s process versus people who might have an MCI for other reasons and may not be on an Alzheimer’s trajectory. Although there is not a medication we can put them on, for personal [reasons] it might be valuable for them to understand.
- Lingler JH, Butters MA, Gentry AL, et al. Development of a Standardized Approach to Disclosing Amyloid Imaging Research Results in Mild Cognitive Impairment. Journal of Alzheimer’s Disease 2016;52(1):17-24.