[Editor’s Note: In recognition of the upcoming World Alzheimer’s Day 2025 on September 21, ACRP reached out to Alifiya Tahir, BDS, MPH, Founder and Head of Clinical Operations at Sun Clinical Trials and a member of the ACRP New Jersey Chapter, asking for her perspective on the state of clinical research efforts targeting Alzheimer’s disease. Among other positions prior to starting her new company, Tahir managed a global Phase II trial in Alzheimer’s with Bristol Myers Squibb and was a project manager for immunology and neuroscience trials for Syneos Health. Here is what she shared with us.]
A participant once recounted sitting through 15 cognitive assessments over a 12-month Alzheimer’s study only to withdraw and pursue an U.S. Food and Drug Administration–approved treatment because the trial offered no perceived benefit. This experience underscores the profound impatience—and pragmatic choice—patients face in long-duration, placebo-controlled trials when an approved therapy becomes available.
Alzheimer’s clinical development has moved from decades of disappointment toward cautious optimism. For nearly 20 years, most Phase III programs targeting amyloid ended in futility, leaving clinicians and caregivers disheartened. The approvals of lecanemab (Leqembi) in 2023 and donanemab (Kisunla) in 2024, both shown to modestly slow cognitive decline, marked a turning point. Yet, as one neurologist interviewed by Time cautioned, “what it touches now may arrive too late for many families” (Time, 2025). These advances signal momentum but also reinforce the need for operational excellence if progress is to be sustained.
Challenges
From an operational standpoint, Alzheimer’s trials are among the most demanding in clinical research. Recruitment is notoriously difficult: many trials demand a study partner, cognitive baseline assessments, biomarker confirmation, and frequent site visits. A qualitative review found that burdensome visit schedules, extensive caregiver time commitments, and stringent eligibility criteria—such as excluding comorbidities and requiring imaging—dramatically limit enrollment (Clement et al., 2019; Mitchell et al., 2024). For example, only 10–27% of Alzheimer’s patients meet trial inclusion criteria due to comorbid health issues and logistical constraints (PRNewswire, 2022; Mitchell et al., 2024). Alzheimer’s disease (AD) clinical trials also face one of the high screen failure rates compared to other therapeutic areas. Moreover, less than 1% of eligible U.S. patients are ever referred into clinical studies, highlighting systemic gaps in trial visibility and healthcare integration (USC Schaeffer Center, 2023).
Among recent operational developments, blood-based biomarkers such as plasma tau and amyloid assays with accuracy of more than 90% offer promising screening tools (Shen et al., 2025; Aisen et al., 2025). However, only trials initiated after regulatory approval of these assays can incorporate them; ongoing trials often continue relying on PET imaging or cerebrospinal fluid sampling due to protocol rigidity.
Patient retention poses its own challenges. Data suggest that patients may abandon a trial around six months if they perceive no improvement and choose to pursue available, approved treatments instead, raising statistical bias risks and requiring mitigation strategies (Raman et al., 2024).
Another important but often overlooked operational factor in AD clinical trials is fair compensation. Clinical research ethics and participant equity suggest compensating subjects appropriately for time, effort, and inconvenience. While many sites offer $20–80 per visit (Gabel et al., 2023), patient advisory groups have advocated for flat rates around $200 per visit, particularly when procedures are burdensome, while also covering travel and ancillary costs (STAT, 2024).
Equitable compensation models help recognize the value of participants and—even more—caregiver commitment, and support retention. The caregiver context cannot be ignored. Nearly 70% of caregivers report that coordinating care is stressful and more than 11 million family members in the U.S. provide an average of 31 hours of unpaid care per week (Alzheimer’s Association, 2024). This stress, compounded by trial-related logistics, undermines participation rates and underscores the need to minimize burdens through flexible scheduling, home-based testing, and caregiver support (Alzheimer’s Association, 2024; Disbrow et al., 2020).
Determination
Newer sponsors entering the field, often smaller biotech firms, have introduced novel mechanisms beyond those focused on amyloid, such as regenerative approaches targeting neuronal repair (Nature, 2020). Their agility brings fresh innovation, but limited infrastructure and experience in large, long-duration studies can amplify risks. Unlike established pharmaceutical companies, smaller sponsors often lack established site networks, placing additional reliance on contract research organization partners and creating variability in execution quality. For large, global Phase III programs, the need for repeated imaging, infusion visits, and longitudinal cognitive testing compounds operational complexity.
The growing role of for-profit recruitment centers further highlights both opportunities and concerns. While these centers can accelerate enrollment by leveraging direct outreach and community screening, they raise ethical questions about therapeutic misconception, as documented in a 2023 Los Angeles Times investigation (LAT, 2023). Ensuring truly informed consent and protecting participants from over-medicalization remain core responsibilities of clinical researchers.
The People Behind Progress
Yet even in the most data-driven advances, the human context persists. In Time’s special issue, one patient explained their motivation simply: “I signed up because maybe me sharing my data might mean someone else remembers their father” (Time, 2025). This statement captures why operational rigor is not just about efficiency, but about respecting the immense personal investment participants and caregivers bring to every trial visit.
For the clinical research community, the lessons from Alzheimer’s studies are transferable. Patient-centric design, early biomarker integration, rigorous site support, and adaptive methodologies are not only critical in neurology but will define the next generation of trials across therapeutic areas. The task ahead is clear: to ensure that each trial is not only scientifically robust but also operationally resilient and ethically sound. For Alzheimer’s disease, progress is finally tangible. Whether that progress fulfills its promise will depend as much on the clinical research workforce as on the molecules under investigation.
References
- Clement C., et al. 2019. Challenges to and Facilitators of Recruitment to an Alzheimer’s Clinical Trial. J Alzheimers Dis. PMC6598018.
- Disbrow EA, et al. 2020. Alzheimer Disease and Related Dementia Resources. PMC8637937.
- Gabel M, et al. 2025. Current practices by Alzheimer’s Disease Research Centers (ADRCs). PMC11851152.
- Mitchell AK, et al. 2024. Analysis of eligibility criteria in Alzheimer’s and related dementia clinical trials. Sci Rep.
- PRNewswire. 2022. New national strategy for recruitment and participation in Alzheimer’s disease clinical trials.
- Raman R, et al. 2024. Pre-Randomization Predictors of Study Discontinuation. PMC11266258.
- Shen X, et al. 2025. A Blood Test for Tau: Diagnostic Advances in Alzheimer’s. Time Health Reports.
- USC Schaeffer Center. 2023. Key Barriers for Clinical Trials for Alzheimer’s Disease.
- Alzheimer’s Association. 2024. New Alzheimer’s Association Report Reveals Top Stressors for Caregivers and Lack of Care Navigation Support and Resources.
- Aisen PS, et al. 2025. Advancing the science of recruitment for Alzheimer’s disease clinical trials. J Prev Alzheimers Dis. PMC12321627.
- McKinney H. 2024. Neurologists split on prescribing new Alzheimer’s treatments. STAT News.
- Langbaum JBS, et al. 2023. Recommendations to address key recruitment challenges of Alzheimer’s disease clinical trials. Alzheimers Dement Transl Res Clin Interv. PMC12737.