People who want to participate in clinical trials for Alzheimer's disease face a number of barriers, according to a panel chaired by U.S. experts. Their solutions for addressing this problem were published August 10 in Alzheimer's & Dementia: the Journal of the Alzheimer's Association.
Out of nearly 90 million Americans who may be candidates for a preclinical, prodromal, and mild Alzheimer's disease dementia clinical trial, only 12.5 million ever reach the healthcare system for Alzheimer's disease-related reasons, according to the authors.
"The tallest barriers to more efficient [Alzheimer's disease] clinical trials are those which keep potential volunteers from ever reaching them in the first place," wrote corresponding author Julie Zissimopoulos, PhD, an economist and associate professor at the University of Southern California's Sol Price School of Public Policy.
The group first convened in 2020 in Los Angeles and is composed of 35 experts representing a wide range of stakeholders. Their aim was to assess the critical challenges facing Alzheimer's disease clinical trials, particularly those associated with bottlenecks in trial recruitment.
Among such barriers, the panel identified the following:
- Limited awareness of early asymptomatic and symptomatic stages of Alzheimer's disease
- Fear of and lack of a clear Alzheimer's disease diagnosis
- Limited access to diagnostics, such as PET scans
- Overstretched healthcare providers and infrastructure
- Infrequent trial referrals
- Inadequate engagement of people from racial and ethnic backgrounds who have historically been underrepresented in clinical research.
The study authors identified 27 solutions for these barriers that have the potential to accelerate the conduct and execution of Alzheimer's clinical trials, which they grouped into the following broad categories:
Cognitive screening and early detection
- Assess innovative community-engaging prescreening strategies such as virtual engagement outreach and digital assessment tools to facilitate early diagnosis, trial recruitment, and trial retention
- Encourage the U.S. Centers for Medicare and Medicaid Services to incentivize primary care physicians to execute annual wellness visits with cognitive screening and reimburse diagnostics, such as amyloid PET scans for individuals with symptomatic cognitive impairment, to increase trial enrollment
Blood-based biomarker testing
- Develop accurate, accessible, and affordable blood-based biomarker tests to support trial enrollment
- Build a centralized data-sharing platform with data collected on biomarker types, imaging, autopsy, co-pathology, and socioeconomic status to facilitate the identification and analysis of phenotypes across heterogeneous populations
Public awareness and outreach
- Initiate brain health awareness campaigns targeting diverse communities to promote the benefits of early screening and diagnosis, and activate asymptomatic individuals to participate in Alzheimer's disease registries and clinical trials
- Develop awareness campaigns to promote uptake of cognitive screening at annual wellness visits, targeting both communities and primary care physicians
Clinical trial architecture in the community
- Leverage networks of satellite sites to take trials to the community, while also using mobile trial units, community diagnostic clinics
- Work with local community leaders in faith- or culturally based organizations to build trust and provide information about Alzheimer's disease clinical trials
Screen-fail registry and digital engagement
- Build a screen-fail registry to collect and share basic participant data during trial prequalification as well as after screen failure to improve trial matching and referrals
- Build a digital engagement strategy and platform to enroll self-identified individuals into multiple Alzheimer's disease clinical trials simultaneously
Virtual clinical trials
- Leverage integrated, home-based computerized cognitive assessments and video conferencing to reduce burden on participants and study partners
- Increase use of virtual procedures for safety monitoring and remote assessment of cognition and function
Clinical trial design optimization through quantitative modeling
- Use quantitative modeling and simulation tools that leverage open patient-level data from Alzheimer's disease clinical trials integrated into regulatory-grade standardized database, to develop clinical trial simulators with three basic components: disease progression, drug effects, and trial features such as placebo effect and dropouts
- Submit such simulators through formal regulatory pathways
Ultimately, absent effective therapies, the prevalence of dementia is expected to triple over the next several decades, and by 2050, an estimated 12.7 million Americans will be living with Alzheimer's disease dementia, the authors wrote.
Clinical trials are crucial to expedite the development of novel therapies.
Future studies and panels should consider the cost implications of these proposed solutions, as well as specific actionable steps for implementing solutions and a framework for markers of success, the authors wrote.
"Above all, the critical barriers facing [Alzheimer's disease] clinical trials today can be overcome when stakeholders from academia, industry, philanthropy, government, and volunteers work together to address this immense public health challenge," Zissimopoulos and colleagues concluded.
