Physicians’ Assessment of the Clinical Utility of a Novel Test to Diagnose Alzheimer’s Disease (AD)

Physicians’ Assessment of the Clinical Utility of a Novel Test to Diagnose Alzheimer’s Disease (AD)

Background:

Alzheimer’s disease (AD) is a neurodegenerative disease with a complex and multifaceted pathology. Several factors including genetics, lifestyle, and environmental factors are known to

impact the risk of AD. As the most common cause of dementia affecting over 6 million Americans over age 65, AD has a substantial burden on patients and caregivers. There is also significant indirect and direct cost burden of treating and managing AD and dementia. Currently, there is no single, definitive modality for AD diagnosis and historically, AD diagnosis has been made using non-specific tests (imaging and/or CSF biomarkers).

There are several unmet needs and challenges with current AD diagnostic tools for a patient with suspected dementia including inaccurate sensitivity and specificity, lack of a single test that can definitively diagnose AD and distinguish it from other forms of dementia, and inability to comply with the U.S. National Institutes of Health (NIH) “Gold Standard” for diagnosing AD.

The current diagnostic pathway may not only lead to frustration and anxiety for patients and family members but may also negatively impact patient management. A more definitive diagnosis could help physicians prescribe effective treatments, provide optimized care, and enable enrollment in clinical trials where appropriate.

DISCERN^™ is a novel test combining three biomarkers: Morphometric Imaging (measures fibroblasts ability to form networks), Protein Kinase C ε (measures synaptic growth), and AD-Index (measures phosphorylation of Erk1 and Erk2 in response to bradykinin). DISCERN^™ is the only AD diagnostic validated against autopsy confirmed diagnosis (NIH gold standard for AD diagnosis) with 95% sensitivity and 95% specificity. This research explores the clinical utility of the novel DISCERN^™ test.

Purpose/Objectives:

A web-based survey conjoint analysis estimated preferences from a sample of PCPs,

neurologists, and geriatricians. Hypothetical patient profiles were created via computer software with five attributes: MRI/CT Scan results, MMSE score, Blood test results (TSH, Vitamin B12, Folate, Syphilis, Lyme disease), Age, and DISCERN^™ test result. Physicians viewed seven randomly selected profiles from a fractional factorial design of 27 unique profiles using a

least-fill methodology. For each patient, physicians indicated whether or not they would diagnose AD, prescribe medications for AD cognitive impairment, refer to a neurologist (PCPs and geriatricians only), or prescribe futuristic disease-modifying Drug X. Aggregate logit models assessed attribute importance.

Methods:

402 physicians participated (250 PCPs, 102 Neurologists, 50 Geriatricians). Only 4%

physicians indicated extreme satisfaction with current AD tests. Results indicate physicians will routinely use the results of DISCERN^™ in the diagnosis and management of AD, with 90% indicating they would likely order DISCERN^™. The study demonstrated DISCERN^™ was an important attribute in physician decision-making and compared to no DISCERN^™ test a positive DISCERN^™ result was associated with: significantly higher odds of AD diagnosis (relative attribute importance (RAI):64%; OR:6.45; 95% CI:5.09-8.17), prescribing Drug X (RAI:62%; OR:4.12; 95% CI:3.36-5.04), and prescribing treatments for cognitive impairment (RAI:54%; OR:2.98; 95% CI:2.40-3.68); a negative DISCERN^™ test was associated with significantly lower odds of prescribing treatments for cognitive impairment (RAI:54%; OR:0.58; 95% CI:0.48-0.70), and definitively diagnosing AD (RAI:64%; OR:0.39; 95% CI:0.32-0.48); MMSE score was the most important attribute in decisions to refer to a neurologist (RAI:48%). The DISCERN^™ test result was the most important attribute in 3 out of 4 physician decision-making outcomes.

Results:

Results demonstrate that 90% of physicians would routinely use the results of DISCERN™ and the test was an important attribute in physician decision-making and, compared to no DISCERN™ test, a positive result was associated with significantly higher clinician confidence in an AD diagnosis, even earlier in the disease. This result confirms the test’s value as a promising breakthrough for early diagnosis of AD.

The study also found that a positive DISCERN™ test was associated with significantly higher odds of prescribing disease modifying agents for AD, with the MMSE score being the most important attribute in the decision to refer a patient to a neurologist.

The results indicate that physicians see value in the information from the DISCERN™ test and would order this test to make clinical decisions compared to current SOC tests. This study provides evidence demonstrating the clinical utility of the DISCERN™ test and has implications for clinicians considering adoption of this test and payers evaluating coverage of the test.

This study was funded by SYNAPS Dx.

Conclusions:

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