Nearly 20 years of research have yielded only one FDA-approved drug for treating Alzheimer’s disease. And even that lone therapy, aducanumab (Aduhelm), has struggled to win broad trust on efficacy.
As one multidisciplinary panel sees it, the prime issue is the clinical rigor of the research. But the problem isn’t with the science per se. It’s in the need for many more patient participants.
The demand is especially great, the team notes, for asymptomatic individuals of all races and ethnicities.
This month the panel—which engaged representatives from academia, patient-advocacy organizations, philanthropy, nonprofit orgs, government and industry—published a detailed analysis of the opportunity in Alzheimer’s & Dementia, the official journal of the Alzheimer’s Association [1].
More needs to be done to attract participants, they suggest, because clinical trials for Alzheimer’s disease are not only slower to enroll subjects but also cost more and take longer than trials in many if not most other therapeutic areas.
The paper’s corresponding author is healthcare economist Julie Zissimopoulos, PhD, of the University of Southern California. Senior author is USC neurologist Paul Aisen, MD.
The article includes a comprehensive set of recommendations aimed at addressing the key patient-recruitment challenges facing researchers who wish to conduct robust clinical trials on treatments for Alzheimer’s disease.
Here are sample recommendations under five of the eight categories the authors describe.
1. Encourage broader cognitive screening and earlier detection in healthy, asymptomatic as well as symptomatic, early stage, older adults.
- Assess innovative community-engaging prescreening strategies such as virtual engagement outreach and digital assessment tools to facilitate early diagnosis, trial recruitment and trial retention.
- Develop communication streams with primary care physicians around training and resources to keep them informed about ongoing clinical research.
2. Develop accurate, accessible and affordable blood-based biomarker tests to support trial enrollment—and address the practical issues related to their integration in clinical practice.
- Provide a shared resource of blood samples to support the comparison and neuropathological validation of different blood-based biomarker assays for Alzheimer’s disease.
- Include blood and cerebrospinal fluid samples, as well as imaging data, in underrepresented groups to establish the generalizability of blood tests across heterogeneous populations.
3. Build public awareness and conduct outreach efforts.
- Develop awareness campaigns to promote uptake of cognitive screening at annual wellness visits, targeting both communities and primary care physicians.
- Initiate awareness campaigns targeting healthcare providers to promote early screening and diagnosis, assessment tools and referrals to Alzheimer’s clinical trials.
4. Conduct virtual clinical trials.
- Leverage integrated, home-based computerized cognitive assessments and video conferencing to reduce burden on participants and study partners.
- Increase number of remote nurses to visit participants at home to perform key lab tests and physical exams, administer therapy and ensure the integrity of data collected remotely.
5. Optimize clinical trial design 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. Make sure clinical trial simulators include three basic components—disease progression, drug effects and trial features such as placebo effect and dropouts.
- Submit such simulators through formal regulatory pathways for their review and potential endorsement (for example, FDA’s Fit for Purpose Initiative, European Medicines Agency’s Qualification of Novel Methodologies in Drug Development).
Other activity categories laid out in the present paper include clinical trial architecture in the community, screen-fail registry and digital engagement, and additional measures such as targeting potential patients via EHR data and capturing reasons participants give for dropping out of trials.
The authors cite demographic research showing that, if safe and effective therapies fail to reach commercialization in coming months and years, well more than 12.5 million Americans will be living with Alzheimer’s dementia by 2050.
At present the count is already believed to be north of 6 million.
Zissimopoulos and colleagues urge researchers and future panel members to plan “specific actionable steps for implementing solutions and a framework for markers of success. Extensions should consider the applicability of the recruitment strategies to various targets of Alzheimer’s disease trials, for example those that target the functional and behavioral symptoms of dementia.”
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These additions will provide key information to federal agencies, national advocacy and local community-based organizations, trial sponsors, diagnostic companies, healthcare providers and provider organizations, health insurers, the research community and the public. 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 and find novel ways to expedite the development of therapies for Alzheimer’s disease.”
The article is available in full for free.
Dave P. has worked in journalism, marketing and public relations for more than 30 years, frequently concentrating on hospitals, healthcare technology and Catholic communications. He has also specialized in fundraising communications, ghostwriting for CEOs of local, national and global charities, nonprofits and foundations.