Quality Improvement and Clinical Utility PrecivityAD2(TM) Clinician Survey

Study Overview
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Brief Summary
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There is a major unmet need for timely, non-invasive, and low-burden evaluation of patients presenting with mild cognitive impairment (MCI) and dementia. MCI impacts 12-18% of people in the United States over age 60 years (Alzheimer's Association. Mild Cognitive Impairment (MCI) available at https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/mild-cognitive-impairment. Accessed August 16, 2022). MCI does not substantially interfere with daily activities, although complex functional tasks may be performed less efficiently (Knopman DS, Petersen RC. Mild cognitive impairment and mild dementia: a clinical perspective. Mayo Clin Proc. 2014;89(10):1452-1459. doi:10.1016/j.mayocp.2014.06.019). Approximately 30% of MCI patients have Alzheimer's disease (AD) as a cause of their symptoms (Lopez,OL, Kuller LH, Becker JT, et al. Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study. Arch Neurol. 2007;64(3):416-420.doi:10.1001/archneur.64.3.416)). In contrast, dementia is defined by chronic, acquired loss of two or more cognitive abilities caused by brain disease or injury, often associated with significant interference with the ability to function at work or at usual activities. (Knopman DS, Petersen RC. Mild cognitive impairment and mild dementia: a clinical perspective. Mayo Clin Proc. 2014;89(10):1452-1459. doi:10.1016/j.mayocp.2014.06.019). Approximately 60-80% of dementia patients have AD as a cause of their symptoms (Alzheimer's Association. Mild Cognitive Impairment (MCI) available at https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/mild-cognitive-impairment. Accessed August 16, 2022).

Detailed Description
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The Quality Improvement PrecivityAD2(TM) Clinician Survey and Clinical Utility Study (QUIP II) represents a large-scale initiative for the PrecivityAD2 blood test for use by neurologists, geriatricians, and geropsychiatrists (memory care specialists) who see patients aged 55 years and older with signs or symptoms of MCI or dementia. C₂N Diagnostics, LLC is a CLIA-certified, CAP-accredited diagnostic testing laboratory based in St. Louis, MO. Its new test, the PrecivityAD2 blood test, measures plasma amyloid beta (Aβ) peptides 42 and 40 (Aβ42/40) Ratio and phosphorylated tau (p-tau) compared to non-phosphorylated tau (np-tau) at amino acid 217 of the tau peptide (p-tau217/np-tau217) ratio to determine whether a patient with signs or symptoms of cognitive impairment is likely to have brain amyloid plaques, a pathological hallmark of AD.

Official Title
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Quality Improvement PrecivityAD2(TM): A Survey and Clinical Utility Study of the PrecivityAD2 Blood Test in the Evaluation of Cognitive Impairment (QUIP II)

Conditions
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Dementia, Alzheimer Disease, Mild Cognitive Impairment, Cognitive Decline, Cognitive Impairment, Memory Impairment

Intervention / Treatment
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* Other: PrecivityAD2(TM) blood test


Participation Criteria
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Eligibility Criteria
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Physician Inclusion Criteria: Memory care specialists actively practicing in the United States Practice serves individuals with MCI or dementia age > 55 years Average patient volume > 25 visits per week (all patients seen across practice) Memory care specialist with access to an online electronic survey Physician Exclusion Criteria: 1) Clinicians who practice in New York Participant Inclusion Criteria: Individual with MCI or dementia Age >= 55 years Participant Exclusion Criteria Individual requiring test related blood draw within the state of New York Participation does not seem to be in the best interest of the individual, per the ordering clinician

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>One time clinician survey post-test following the receipt of the PrecivityAD2 blood test result | Other: PrecivityAD2(TM) blood test<br>* The PrecivityAD2 blood test measures plasma amyloid beta (Aβ) peptides 42 and 40 (Aβ42/40) Ratio and phosphorylated tau (p-tau) compared to non-phosphorylated tau (np-tau) at amino acid 217 of the tau peptide (p-tau217/np-tau217) ratio to determine whether a patient with signs or symptoms of cognitive impairment is likely to have brain amyloid plaques, a pathological hallmark of AD.<br>* Other names: AD2;|
| Cohort B<br>Pre-test as well as post-test and close-out survey following the receipt of the PrecivityAD2 blood test result | Other: PrecivityAD2(TM) blood test<br>* The PrecivityAD2 blood test measures plasma amyloid beta (Aβ) peptides 42 and 40 (Aβ42/40) Ratio and phosphorylated tau (p-tau) compared to non-phosphorylated tau (np-tau) at amino acid 217 of the tau peptide (p-tau217/np-tau217) ratio to determine whether a patient with signs or symptoms of cognitive impairment is likely to have brain amyloid plaques, a pathological hallmark of AD.<br>* Other names: AD2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in planned clinical management (Cohort A and B) | The association of the test result on medical decision making | Day 20 | 
| Change in planned clinical management (Cohort B) | Evaluate the planned versus subsequent planned change in clinical management as a result of receiving the test result | Day 0 vs Day 20 | 
| Difference between the actual age and symptomatology versus intended use criteria (Cohort A and B) | Evaluate the intended use criteria | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between the test result and actual clinical management (Cohort B) | Association of the test result on subsequent conducted changes in clinical management and test results when evaluating individuals with MCI or dementia in an ambulatory setting | Day 90 | 
| Change in planned clinical management compared to conducted clinical management (Cohort B only) | The evaluation of planned versus conducted change in management as a result of receiving the test result | Day 20 vs Day 90 | 
| Change in probability of AD (Cohort A and B) | Evaluate the probability of an AD Dx pre and post receipt of the test result | Day 0 vs Day 20 | 
| Change in anti-AD medication use (Cohort A and B) | Evaluate anti-AD medication use pre- and post-receipt of the test result | Day 0 vs Day 20 | 
| Change in diagnosis (Cohort B) | Evaluate any changes in diagnoses as a result of receiving the AD test result | Day 0 vs Day 90 | 
| Relationship between the test result and planned testing (Cohort B) | Evaluate the association between subsequent test ordering pre and post testing | Day 0 vs Day 20 vs Day 90 | 
| Correlations between the net promoter score and ease of use by APS2 result (Cohort B) | Focus group questions around net promoter score and ease of use, strengths, and limitations of testing | Day 90 |