Objective: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.Methods: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single‐arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing.Results: A 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti‐AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001).Interpretation: These findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.

More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer's disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD ^® blood test, a clinically validated BBM test for the evaluation of brain amyloid, a pathological hallmark of AD. The model compared 2 scenarios: (1) baseline testing involving usual care practice, and (2) early use of a BBM test before usual care CSF and PET biomarker use. At a modest 40% adoption rate, the BBM test scenario had comparable sensitivity and specificity to the usual care scenario and showed net savings in the diagnostic work-up of $3.57 million or $0.30 per member per month in a 1 million member population, translating to over $1B when extrapolated to the US population as a whole and representing a 11.4% cost reduction. Savings were driven by reductions in the frequency and need for CSF and PET testing. Additionally, BBM testing was associated with a cost savings of $643 per AD case identified. Use of the PrecivityAD blood test in the clinical care pathway may prevent unnecessary testing, provide cost savings, and reduce the burden on both patients and health plans.

Objective: The objective of this study was to assess clinical decision-making associated with the use of a multi-analyte blood biomarker (BBM) test among patients presenting with signs or symptoms of mild cognitive impairment or dementia. Methods: The Quality Improvement PrecivityAD2 (QUIP II) Clinician Survey (NCT06025877) study evaluated the clinical utility of the PrecivityAD2™ blood test in a prospective, single cohort of 203 patients presenting with symptoms of Alzheimer’s disease (AD) or other causes of cognitive decline across 12 memory specialists. The PrecivityAD2 blood test (C2N Diagnostics, St. Louis, MO) combines the plasma Aβ42/Aβ40 ratio and the p-tau217/np-tau217 ratio (%p-tau217) measurements in a statistical algorithm to yield an Amyloid Probability Score 2 (APS2) that informs on the likelihood of brain amyloid plaques. After receiving the BBM test results, clinicians completed surveys on management strategies for each patient. Results: Patients had a median age of 74, 53% were female, and 28% were traditionally under-represented in Black, Hispanic, and Asian groups. The composite primary endpoint, defined as a change in AD diagnostic certainty, drug therapy, or additional brain amyloid evaluation pre- and post-BBM testing, was 75% (p < 0.0001 versus the pre-specified threshold of 20% clinically meaningful change). Anti-AD medication orders decreased among negative APS2 patients and increased among positive APS2 patients (p < 0.0001). Additional brain amyloid testing decreased among negative APS2 patients (p < 0.0001). Conclusions: This blood biomarker test can help memory specialists guide patients to anti-AD therapies as well as rule out AD to allow for other diagnostic considerations.

Background/Objectives: A high-performing blood biomarker (BBM) test for Alzheimer’s disease (AD) represents an accurate, accessible, and scalable tool to aid healthcare professionals (HCPs) evaluating patients presenting with signs or symptoms of mild cognitive impairment (MCI) or dementia. However, implementation of AD blood tests into clinical practice has not been extensively evaluated. The objective of this study was to assess the implementation of the multi-analyte PrecivityAD2™ blood test (C2N Diagnostics, LLC, St. Louis, MO, USA) into the clinical workflow of memory care clinics. Methods: A total of 8 HCPs (neurologists, geriatricians, geriatric psychiatrists) who served as site directors from 8 outpatient sites that evaluated 203 cognitively symptomatic patients were included in this sub-study of the real-world QUIP II Study (NCT06025877). Implementation of this blood test was assessed through surveying these HCPs using published frameworks including the Technology Acceptance Model, net promoter score, and forced choice preference questions. These assessments were analyzed using Wilcoxon signed-rank test, Fisher’s Exact test, and Wilcoxon signed-rank test, respectively. Results: HCPs reported acceptance scores that averaged 9.6 out of 10 (p < 0.0001, effect size 0.840): the test’s contribution to clinical decision-making as well as the ease of understanding test results received the highest ratings. The net promoter score was 75 (p < 0.0001), exceeding the typical benchmark of 30 reported as good levels of satisfaction in healthcare settings. The APS2 results and individual blood analyte results were rated with similar preference around their roles in HCP clinical decision-making. Conclusions: The results indicate early evidence of user acceptance and recognition by HCPs that this AD blood test can personalize the clinical care pathway for evaluating cognitively symptomatic patients.

Background: Blood biomarkers (BBMs) represent an acceptable, accessible, equitable, and scalable alternative to amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers to help establish an Alzheimer's disease diagnosis. The PrecivityAD2 test (C2N Diagnostics, St. Louis, MO) is a multi‐analyte assay with algorithmic analysis (MAAA) BBM test that detects presence of brain amyloid plaques with high diagnostic accuracy among patients undergoing evaluation for cognitive impairment. While the clinical validity of the PrecivityAD2 test has been established, its budgetary impact has not been well described. Method: Our budget impact model, based on a decision tree that considered a one million (1MM) US health plan population, evaluated the effects of PrecivityAD2 test adoption as a first evaluation at the neurologist's office versus the first current standard use of PET or CSF testing in patients with cognitive impairment. We used estimates of real‐world adoption, adherence, and drop‐out measures drawn from clinical expert opinion as well as clinical utility study data, rather than idealized scenarios, to simulate clinical practice more closely. Result: A clinical pathway using the PrecivityAD2 test early in the evaluation process had improved sensitivity (90.1% vs 93.5%) and reduced specificity (92.3% vs 84.8%) as compared to usual care utilizing PET or CSF biomarkers as first‐line biomarker testing. Net savings from PrecivityAD2 test use in the diagnostic work‐up was $10.9MM or $0.91 per member per month (PMPM) in this 1MM lives model, representing a 26.2% reduction in total costs for AD evaluation. Among diagnosed cases in the model, PrecivityAD2 testing resulted in cost savings of $2,753 and $3,578 per case identified at 40% and 100% test penetration, respectively. Savings were driven by reductions in utilization of PET and CSF testing. The potential for economic impact is significant: at a 40% adoption rate, savings to the US healthcare system could exceed $3.5B dollars. Conclusion: In a budget impact model, PrecivityAD2 testing prior to usual care brain amyloid detection methods in patients undergoing evaluation for cognitive impairment provides cost savings and reduces the predicted burden on both patients and payers, while maintaining a high quality of care.