Alzheimer's plasma biomarkers: an LAR consent pathway, built up front
Top-tier global diagnostics manufacturer · clinically-confirmed Alzheimer's plasma biomarker collection · 200 subjects (+10 screen failures), up to 5 sites
The challenge the client gave us
A top-tier diagnostics manufacturer is developing a plasma-based Alzheimer's biomarker assay. It needs specimens from clinically confirmed Alzheimer's disease patients — confirmed by neurological exam, cognitive/functional testing, and imaging (MRI/CT/PET) or CSF/blood, with MMSE ≤ 24 and age ≥ 60 — not cognitively normal volunteers standing in for patients.
The catch is two-sided. First, cognitive impairment makes informed consent harder: many of these patients cannot legally consent for themselves, so the study only works if a legally authorized representative (LAR) consent pathway is built into the protocol from the start. Second, confirmed Alzheimer's patients are concentrated in specific practices — neurology, psychiatry, geriatric medicine, and some family medicine — not spread evenly across a research-site network.
At a glance
| Subjects | ~400, split between cognitively normal controls and clinically confirmed Alzheimer's |
| Confirmed-AD arm | Clinically confirmed AD; MMSE ≤ 24, age ≥ 60 (plus reimbursable screen failures) |
| Confirmation basis | Neuro exam, cognitive/functional testing, MRI/CT/PET or CSF/blood |
| Sites | Up to 5, across neurology, psychiatry, geriatric medicine, family medicine |
| Specimen | Plasma — 3 × 10 mL K2 EDTA per subject, 1 mL aliquots |
| Cold chain | 2–8 °C within 6 hrs; frozen ≤ −70 °C within 48 hrs |
| Consent | Operationalized LAR consent for cognitively impaired subjects |
Timeline
- Site targeting Claims-data ranking; highest-density practices first
- Startup Protocol + LAR consent + Part 11 stack
- Activation Up to 5 specialty sites opened
- Enrollment MMSE ≤ 24, age ≥ 60; LAR consent; plasma to spec
- Delivery ~400 subjects; submission-grade set
What we did as a CRO
| CRO responsibility | What RDI did on this study |
|---|---|
| Site selection & feasibility | Ranked physician practices by AD patient volume using insurance claims data and built the network highest-density first — going where confirmed Alzheimer's patients actually are (neurology, psychiatry, geriatric, family medicine) rather than to the easiest sites to open |
| Regulatory & study start-up | Built the LAR consent pathway up front and ran a 21 CFR Part 11 CTMS/EDC/eTMF stack so the documentation was submission-grade from day one |
| Site activation & training | Activated up to 5 sites and partnered with the practices that could actually deliver confirmed, consentable AD patients |
| Recruitment & enrollment | Confirmed AD by neuro exam / cognitive-functional testing / imaging or CSF, screened to MMSE ≤ 24 and age ≥ 60; for cognitively impaired subjects, coordinated the LAR to be present with the patient so consent and the blood draw happened in one visit |
| Kits, samples & lab | Collected plasma to spec — 3 × 10 mL K2 EDTA, 1 mL aliquots, 2–8 °C within 6 hrs and frozen ≤ −70 °C within 48 hrs |
| Monitoring & data | Central monitoring on the Part 11 stack; captured confirmation basis and consent pathway per subject |
| Project management & close-out | Delivered ~400 subjects split between cognitively normal controls and confirmed AD (plus reimbursable screen failures) against the specimen spec |
What made it hard
- Many subjects can't consent for themselves. Without a working LAR pathway, the protocol simply can't enroll the confirmed-dementia patients the assay is meant for.
- The patients are concentrated, not distributed. Confirmed Alzheimer's diagnosis lives in specific neurology, psychiatry, geriatric, and family-medicine practices — a general research-site list won't reach them efficiently.
- Confirmation is demanding. MMSE ≤ 24 and age ≥ 60 is only the screen; clinical confirmation rests on neuro exam, cognitive/functional testing, and imaging or CSF.
- The specimen spec is strict — K2 EDTA plasma on a tight cold-chain clock to ≤ −70 °C, where any handling slip costs a hard-to-recruit subject's sample.
How we solved it
- We built the LAR consent pathway up front, so the protocol could enroll the patients the sponsor actually needed instead of stalling on capacity-to-consent.
- We coordinated the legally authorized representative to be there with the patient. For dementia subjects who can't consent for themselves, we scheduled around the LAR so consent, cognitive confirmation, and the blood draw happened in one trip.
- We found the sites through claims-data targeting. Instead of a generic site list, we ranked physician practices by Alzheimer's patient volume from insurance claims and went highest-density first — then partnered with the practices that could actually help deliver confirmed, consentable patients.
- We ran everything on a 21 CFR Part 11 stack, so the specimens arrived with submission-grade documentation attached.
The result
A turnkey model for diseases that affect a patient's capacity to consent: claims-data site targeting to find the concentrated patient population, plus operationalized LAR consent to actually enroll them. The collection delivered ~400 subjects split between cognitively normal controls and clinically confirmed Alzheimer's (plus reimbursable screen failures) across up to 5 specialty sites, on a submission-grade plasma specimen set.
Source: RDI program scope and specimen specification; Diagnostica™ at program close. Sponsor identity withheld per confidentiality terms; site labels anonymized. Operations report, not a clinical-results publication.