A new study on biomarker variation highlights implications for clinical trial recruitment, access, and participation
Alzheimer’s clinical trials are increasingly targeting early, biomarker-defined stages of disease. This shift reflects a growing consensus that earlier intervention is likely to have the greatest impact for patients, their families, and the healthcare system. But it also introduces a core recruitment challenge: eligibility now depends on how consistently we can measure and interpret biomarkers across populations.
What new research shows
New research adds important nuance to this issue. A study published in Alzheimer’s & Dementia by USC researchers suggests that buildup of tau protein (an early biomarker for Alzheimer’s disease) may vary across racial and ethnic groups. Among Black and Hispanic participants, researchers observed higher levels of tau in key memory-related brain regions compared to non-Hispanic white participants, even prior to amyloid buildup typically associated with Alzheimer’s. These findings could explain the high screen fail rates that have been seen in recent studies as sponsors have worked diligently to recruit under-represented populations.
The study also finds that the relationship between these biomarkers and cognitive performance is not uniform. While higher tau levels are associated with worse memory overall, amyloid appears to strengthen this relationship in some groups but not others. These findings suggest that the biological signals used to define early Alzheimer’s and to determine trial eligibility may not operate identically across populations.
Importantly, the study highlights measurement challenges as well. Some observed differences in tau may reflect limitations of current imaging tracers, which can produce off-target signals. As biomarker-based approaches become more central to both research and clinical care, ensuring that these tools are validated across diverse populations will be critical.
Implications for recruitment science
For recruitment science, the implications are significant. Many Alzheimer’s trials rely on biomarker thresholds to identify early-stage disease, but those thresholds are typically calibrated on specific study populations. If biomarker levels, and their relationship to disease progression, vary across groups, it is not yet clear whether standard cutoffs identify comparable patients across populations.
This raises several considerations for trial design and recruitment:
- Eligibility criteria: Biomarker-based thresholds may not map cleanly onto equivalent disease stages across populations, complicating how eligibility is defined and applied.
- Interpretation: Trials assume a stable relationship between biomarkers and disease progression; emerging evidence suggests this relationship may be more complex.
- Representation: Differences in how disease manifests biologically may contribute to variation in who is identified as eligible for trials, an issue that warrants further study.
More broadly, these findings intersect with a well-documented challenge: Alzheimer’s clinical trial populations remain disproportionately white, and demographic reporting is often incomplete. Together, these gaps limit our ability to assess whether trial populations, and ultimately treatment effects, are representative of the broader patient population.
These problems are not easy to solve. Drugmakers running clinical trials usually reserve the most expensive screening procedures for participants most likely to enroll. One notable effort to help close these data gaps is a recent large study providing access to comprehensive biomarker data, with a quarter of participants coming from underrepresented groups.
The bottom line
The takeaway for recruitment science is straightforward but important. As Alzheimer’s research moves toward earlier, biomarker-defined disease, that means recruitment and enrollment strategies and eligibility criteria are increasingly becoming interrelated decisions.
Advances in science are refining how Alzheimer’s is detected and defined. Ensuring that these advances translate into inclusive and representative clinical trials will require equal attention to how biomarkers are measured, interpreted, and operationalized across populations.
Phyllis Barkman Ferrell is a Nonresident Scholar at the USC Schaeffer Institute for Public Policy & Government Service and co-leads the USC Clinical Trial Recruitment Lab.
