What Matters Most? New Research Identifies Treatment Needs and Priorities of the Alzheimer’s Community

Alzheimer’s disease is one of the most complex challenges facing the scientific community, but there are some bright spots in Alzheimer’s research. Thanks to research conducted by the Alzheimer’s Disease Patient and Caregiver Engagement (AD PACE) initiative, the treatment priorities of people impacted by Alzheimer’s are now coming into sharper focus.

The public-private partnership, which is led by the nonprofit group UsAgainstAlzheimer’s, joins patients and care partners, leading pharmaceutical companies (including founding sponsor Lundbeck), academics and government agencies in a unique pre-competitive collaboration to assess treatment needs of Alzheimer’s patients and care partners. Through the groundbreaking What Matters Most (WMM) study, AD PACE is generating scientifically validated data about the real-world impact of Alzheimer’s, along with first-of-its-kind findings on the treatment-related outcomes that matter most to people with Alzheimer’s and their care partners. These insights will help researchers design clinical trials with more clinically meaningful, patient-centered endpoints.

Results of the first phase of this research were recently published in the journal Alzheimer’s Research & Therapy, and preliminary results of the second phase were presented in a poster at the 2020 Alzheimer’s Association International Conference (AAIC). Ann Hartry, Lundbeck’s vice president of Health Economics Outcomes Research, is co-author of both publications and serves on the AD PACE Steering Committee. Here, she provides an overview of the latest findings and shares what it may mean for the future of Alzheimer’s research.

Why is this research necessary? Haven’t patients’ needs always been at the heart of Alzheimer’s research programs?
Ann Hartry: Everyone connected to Alzheimer’s research is committed to improving people’s lives in meaningful ways. But the disconnect is that up to now, the treatment priorities of the Alzheimer’s community have not been scientifically validated. Clinical trials were designed around endpoints that we assumed were important to patients and care partners, but – to date – we have not been able to say with validated certainty that these endpoints were most meaningful to the Alzheimer’s community.

Understanding what matters most to the community, then making sure we have the tools to accurately measure progress toward those important aspects of the disease will help us best meet the needs of people impacted by Alzheimer’s and could lead to more meaningful trials. 

So, what does matter most? What is the key take-away from Phase 1 of the What Matters Most study?
AH: This study was really the first research to look at patients’ and caregivers’ needs with scientific rigor. The study involved in-depth interviews with people with Alzheimer’s and care partners across a continuum of Alzheimer’s disease stages—from asymptomatic (identified to be at risk for Alzheimer’s due to the presence of a biomarker) to more advanced stage of disease and care partners. Participants were asked about what matters in a few ways.  They were asked to identify their most common symptoms, the most burdensome symptoms and what they want from a treatment.  The study found that all participants consider improving and restoring memory as the most important treatment-related outcome; but they also indicated that the disease affected not only memory but almost equally communication and concentration.  

That doesn’t seem like a breakthrough finding—wouldn’t you expect people in an Alzheimer’s study to be most concerned about restoring memory?
AH: While the results aren’t entirely surprising, they are nonetheless meaningful because we can now say with scientific validity we understand what matters most to this community.

Also noteworthy was the finding that people who were asymptomatic at the time of the study endorsed memory issues as a challenge. Considering they were clinically categorized as asymptomatic, but voiced concerns about short-term memory loss, the research suggests we may need to improve our measurement tools for early-stage disease. This is particularly important because recent guidance from the US Food and Drug Administration (FDA) stressed that outcome measures used to assess treatment effectiveness in early Alzheimer’s disease should represent clinically meaningful changes. To measure clinically meaningful changes, we need to make sure we’re assessing the right symptoms and using the right measurement tools. 

Phase 2 of this research quantified the findings from the first phase and examined current Alzheimer’s assessments. What did that research find?
AH: The goal of Phase 2 was to understand more clearly which impacts were most important to patients and caregivers, and then to evaluate existing measures and see how well they align to the treatment priorities of patients.

There is some indication that the assessments we use to measure improvement in symptoms and the effectiveness of a potential therapy may not provide a full picture of the disease, particularly for people with mild or mild-moderate Alzheimer’s. For example, some of the most-used measures center on a person’s functioning but don’t give us any indication of the emotional and psychological impacts of the disease. Or a measure might tell us if someone can remember a series of words from a few minutes prior, but not if that patient will remember how to use the microwave, follow a conversation or experience anxiety when she can’t remember whether she took her medication.

Our research on current assessments is preliminary, but the research indicates that we have pretty good assessments. The challenge is in applying the assessments to the endpoints that match what patients really want. For example, if you’re studying a therapy’s effectiveness at improving a person’s ability to perform activities of daily living, the cognitive assessments may not be the right way to go. It may be that a trial needs a combination of cognitive assessment with a quality of life assessment that more accurately measures emotional wellbeing.

What does this mean for the future of Alzheimer’s trials?
AH: Having a very solid body of research into what matters most to Alzheimer’s patients and care partners, and then having broad agreement on the most relevant assessments will help us build smart Alzheimer’s clinical trials. We will be able to hone in much more precisely on a treatment’s ability to improve (or not) the symptoms that people say matter most.

There’s also the possibility that this research could help guide clinical trial design in other brain diseases. Clinical trials for brain disease treatments have a very high failure rate. This is due to the complexity of the brain, but also partially due to the very subjective nature of so many brain diseases, such as depression. Not all people experience the disease in the same way and not all people have the same treatment goals. Focusing clinical trials around specific patient populations with highly specific treatment outcomes, and then utilizing the right assessments may lead to more meaningful trials and ultimately better quality of life for people with brain diseases. 

Learn more about AD PACE and how people with Alzheimer's and care partners can connect to share insights with doctors, researchers and regulators about What Matters Most.