Early Successes in Remote Research: Enabling Enrollment in Clinical Trials
October 30, 2024
Dr. King shared these compelling words on March 25, 1966, before the Second Convention of the Medical Committee for Human Rights. Nearly 60 years later, we remember his words as racial inequities persist in healthcare, especially in research, care, and treatment for people with dementia.
As we focus on Black History in February, our blog series will take a closer look at the racial inequities impacting Black Americans with Alzheimer’s disease and other causes of dementia. In this blog, we discuss:
- Different types of dementia
- How dementia disproportionately impacts African Americans
- Possible barriers to new anti-amyloid therapies for African Americans
- Underrepresentation of African Americans in dementia trials
What is Dementia?
Dementia is an umbrella term used to describe a group of symptoms related to a progressive decline in cognitive abilities, including memory, language, problem-solving, behavior, and function that impact activities of daily living. According to the Alzheimer’s Association, 6.7 million seniors aged 65+ have Alzheimer’s disease and related dementias. The most common types of dementia include: Alzheimer’s disease, vascular dementia, Lewy body dementia (LBD), and Frontotemporal dementia (FTD).
While Alzheimer’s disease is the most common diagnosis affecting 60-80% of people with dementia, people with different types of dementia share many cognitive symptoms and have a combination of different brain pathologies.
Dementia in African Americans
Approximately 48 million people (14.4%) in the US are African American. According to Us Against Alzheimer’s, there are 5.1 million African Americans over the age of 65 and 1.1 million people in the African American senior population who have some cognitive impairment associated with Alzheimer’s or other causes of dementia.
African Americans have a 2x higher risk of being diagnosed with Alzheimer’s disease – a higher risk than any other racial or ethnic group. In general, Black Americans are more likely to have other symptoms, including agitation/aggression, loss of inhibition, irritability, motor disturbances, abnormal sleep patterns and behavioral changes. Despite this, African Americans often experience diagnostic delays and are more likely to be diagnosed in later stages of dementia.
Sadly, Alzheimer’s disease is the fourth leading cause of death among African Americans over the age of 65. Latest population projection data by age and race indicate that African Americans have the greatest estimated burden of disease due to Alzheimer’s—regardless of age:
By 2060, the risk of Alzheimer's is forecasted to increase fourfold among African American seniors. Not only must we change these inequities for this generation of patients but also for the patients of tomorrow.
Diverse Dementia Pathology in African Americans
In autopsies conducted on decedents with dementia, Rush University researchers found that Black decedents were more likely to have a mixture of different brain pathologies compared with age-, sex-, education-, and cognition-matched White decedents. Following were some notable differences in the pathology patterns:
- White Americans = 2.2x more likely to have AD pathology alone (42% vs. 19.5%)
- Black Americans = 1.6x more likely to have cerebral Infarct (43.9% vs. 27.2%)
So, what does this mean? Because a smaller proportion of Black Americans have amyloid pathology, the recently approved Alzheimer’s treatment, lecanamab, will likely be less prescribed, proportionately, to African Americans. Lecanemab’s trial design excluded patients whose PET scans were negative for amyloid plaque. The drug sponsor, Esai, reported that almost half of African American applicants “screened out” of trial participation compared with 22% of White applicants. Ultimately, only 20 of the 859 (2.3%) trial participants who received lecanemab in the treatment arm were African American.
Why does this matter? First, roughly 20% of the 1.1 million African American seniors are expected to have amyloid pathology alone. As such, there should have been tens of thousands with recent onset who could have screened to participate in this trial.
Second, one of the risks of lecanamab and other anti-amyloid therapies is swelling or bleeding in the brain. Thus, African Americans may not be candidates for anti-amyloid therapies because they have a higher incidence of vascular dementia and may be on blood thinners like Eliquis. Because of these safety concerns, they may not be candidates for anti-amyloid therapies.
However, with only 20 African American participants in the treatment arm, this small sample size leaves neurologists with less than optimal data to to understand how or if lecanemab works differently on African Americans with amyloid plaque buildup, and to understand its safety implications in this underrepresented community that is disproportionately impacted by Alzheimer’s.
Dr. Lisa Barnes, a neuropsychologist at Rush University’s Alzheimer’s Disease Research Center told the Washington Post:
“If we are just targeting amyloid, we can miss a large potential population
that might benefit from treatment.”
Thus, we must encourage drug sponsors to accelerate pre-clinical research and drug development programs addressing other potential causes of cognitive decline. Concurrently, we must change public policy and expand outreach to boost clinical trial enrollment among African Americans.
Underrepresentation in Dementia Trials
Historically, for many reasons, African Americans are underrepresented in clinical trials in many diseases. For example, in the largest study assessing minority enrollment in US clinical trials, researchers analyzed data from 20,692 trials involving 4.76 million trial participants from 2000-2020. The median enrollment of African Americans was 10% – with a concerning 21% of trials reporting zero African American trial participants. This caused the researchers to opine that racism is “an international public health crisis.”
Despite 1993 Congressional mandates to improve minority enrollment, progress has been slow and minority groups remain underrepresented in clinical trials. In another review published in 2021, FDA researchers examined more recent demographic data from 517 trials that were the basis for new drug approvals from 2015-2019. Among the subset of all neurology trials, they reported that trial participation by African Americans had increased to 14.1%, but they also acknowledged the need to examine disease-specific trials.
Dementia trials, in particular, often fail to meet racially appropriate enrollment thresholds. In 2007, when approximately one in three Americans was from a racial or ethnic minority group, a review found that participation by all racial and ethnic minorities in trials for dementia treatments was 10% in NIH-funded trials – but only 3.2% in the trials funded by the pharmaceutical industry. A 2022 review reported a marked improvement. The pooled percentage of diverse racial and ethnic minority participation had increased to 25.6% in dementia trials. However, despite having the highest risk of dementia, trial enrollment by African Americans continues to be low.
The non-profit organization, Us Against Alzheimer’s, reports that 3% of participants in Alzheimer’s drug trials are African American. A random sampling of dementia trials on clinicaltrials.gov affirms the lack of adequate representation. For example, in recent Phase 2 and Phase 3 trials of lecanemab, donanemab, interpirdine, troriluzole, and pimavanserin, the percentage of African American trial participants ranged from a low of 1.5% to a high of 3.2%.
Additionally, approximately one-third of dementia trials fail to report data on the race or ethnicity of their trial participants. In a review of 49 clinical trials of currently marketed treatments for Alzheimer’s disease, only 60% reported the race of trial participants. In another review, researchers looked at data from 100,748 participants enrolled in Phase 2 and Phase 3 dementia prevention studies from 2004 to 2020. Only 62% of trials reported racial/ethnic identities of their participants.
More concerning, because most of these drug trials don’t enroll enough African Americans to reach statistical significance, none of the studies report conclusions about the efficacy or safety/tolerability of their investigational drugs in different racial and ethnic populations. This is more troublesome considering an FDA review of drug approvals between 2008 and 2013 found that approximately one-fifth of new drugs demonstrated some differences in exposure and/or response across racial/ethnic groups.
This lack of diverse clinical trial participation has real life implications. Stephanie Monroe, the director of the African American Network Against Alzheimer’s, spoke about the need to increase African American participation in clinical trials:
“We want to find a cure for Alzheimer’s, but worse than not finding a cure
is finding a cure that doesn’t work for Black people because we haven’t
participated in the research.”
Conclusion
Synapticure can help address some healthcare inequities that continue to persist in dementia clinical trials today. As part of our patient-centric mission, our neurologists talk to our patients about possible clinical trial enrollment, discussing the mechanism of action of trial drugs, along with the risks-benefits of those investigational drugs in relation to our patients’ risk tolerance. We also discuss how to overcome potential barriers to trial participation and have a mental health team who can counsel patients and their family members about any anxiety related to your disease or trial participation.
If you or your family members are interested in learning how you can receive dementia care or clinical trial counseling from the comfort of your home, you can schedule a free consultation online or by calling (855) 255-5917. We would be honored to help you and your loved ones.
1 Our blog series later this month will explore some of the reasons for lack of participation, and offer some potential solutions to increase participation in dementia trials.
ABOUT THE AUTHOR
Amanda Fletcher, MD recently joined Synapticure’s Cognitive Neurology team. Prior to joining Synapticure, Dr. Fletcher specialized in treating people with Alzheimer’s and various related dementias, both in general practice and at ADRCs. She is passionate about addressing health disparities in cognitive neurology and is involved working in communities to help increase clinical trial interest and enrollment. Dr. Fletcher received her undergraduate degree from Jackson State University and her medical degree at Meharry Medical College. She completed her Neurology Residency at the prestigious Barrow Neurological Institute and her fellowship training in Behavioral Neurology and Neuropsychiatry at the renowned Cleveland Clinic Lou Ruvo Center for Brain Health.
