Struggles, strategies identified to better Alzheimer’s clinical trial participation

The continuation of clinical trials for Alzheimer’s disease is dependent upon identification of their challenges as well as strategies for improvement, according to a review published in the April issue of Health Affairs.

Despite numerous advancements that have been made in understanding and treating Alzheimer’s disease, the lack of a cure for the neurodegenerative disease continues to plague the medical community and society as a whole. A vital component in the success of research thus far has been volunteer participation, as participants have taken neuropsychological tests of memory and cognitive function, contributed DNA, blood, and cerebrospinal fluid samples, and undergone brain scans in the name of science.

“The relationship between Alzheimer’s researchers and the public is at a critical juncture,” wrote lead author Jennifer L. Watson, a senior public affairs specialist at the National Institute on Aging in Bethesda, Md., and colleagues. Continued volunteer participation is needed to investigate potential therapies, especially as upcoming trials will test interventions at a presymptomatic stage of the disease.

Watson and colleagues outlined the challenges that remain to increasing enrollment and suggested specific solutions to increase awareness and improve volunteer numbers at all stages of the disease in their review.

The authors cite the following challenges that exist in terms of recruiting volunteers for Alzheimer’s clinical trials: primary care physicians’ lack of capacity and resources to assess cognition and refer patients to research; barriers to participation for underrepresented communities; requirement for a study partner; and the use of invasive procedures.

Given the emphasis on time in clinical practice, it is difficult for many physicians to refer patients to clinical trials for Alzheimer’s disease because often those who are at risk for the disease are older and have a host of other medical issues as well. In addition to a dearth of physician referrals, certain communities are underrepresented. Factors such as longstanding mistrust of the medical community, language barriers, and lack of cultural sensitivity prevent these demographics who are at a higher risk for dementia from participating in trials.

Moreover, these trials generally require a study partner to track cognitive function daily. Previous research has shown that a majority of patients with Alzheimer’s disease do not have a spouse or live alone, which makes this requirement difficult to meet for many. These trials include invasive procedures such as brain scans with radioactive materials and lumbar punctures, which also deter volunteers from participating.

In addition to these established obstacles, new challenges accompany the development of presymptomatic Alzheimer’s disease trials. Evidence has begun to point to underlying pathology that precedes the onset of clinically detectable Alzheimer’s by at least a decade. Researchers are consequently testing interventions that target the preclinical or presymptomatic phase of the disease. “This focus on people who are free of clinical symptoms but at risk for Alzheimer’s disease because of either genetic risk or evidence of Alzheimer’s-related brain changes is new territory and will require genetic or biomarker screening of large numbers of volunteers,” wrote the authors.

Of note is a groundbreaking trial, known as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease, or A4, Trial, that has begun this year. The multisite trial is testing the anti-amyloid immunotherapy solanezumab in 1,000 symptom-free but at-risk older volunteers who have abnormally high levels of the beta amyloid protein in the brain, which is detected with brain imaging. Unfortunately, only a small amount of research has been conducted to determine how healthy people are affected by learning their Alzheimer’s risk status.

Watson and colleagues suggest creating two tiers for recruitment: a general registry of interested people and a second level consisting of those willing to undergo biomarker or genetic testing if selected. They believe that retaining volunteers once they have been selected will be a challenge. “Factors such as study invasiveness and participant burden may be an even greater issue in a symptom-free, albeit at-risk, population,” they wrote.

After delineating the major issues associated with these trials, the authors discussed the following changes that may help solve these problems: bridging the gap between research and clinical care; expanding or coordinating existing registries; modifying trials to increase participant and caregiver access; collaboration among researchers, clinicians, providers, advocates, and others to increase awareness and build trust; and relationships with local underrepresented communities.

“Together, the community of researchers, individuals and families, clinicians, and the public can address barriers and improve the prospects for clinical trials. By doing so, the chances of finding ways to prevent or effectively treat Alzheimer’s disease as soon as possible can be greatly increased,” they wrote.