August 16, 2023
The National Center for Health Research (NCHR) appreciated the opportunity to express our views regarding the Centers for Medicare and Medicaid Services (CMS) proposal to remove the National Coverage Determination (NCD) for beta-amyloid positron tomography (PET Aß) in dementia and neurodegenerative disease that currently stands at one scan per patient per lifetime.
NCHR is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
We support CMS reevaluating coverage for beta-amyloid positron tomography (PET Aß) in dementia and neurodegenerative disease as new treatments targeting amyloid are approved by the Food and Drug Administration (FDA). However, we do not believe that repeating PET Aß scans are the best way to determine the benefits of these new amyloid targeting Alzheimer’s treatments to determine patient outcomes.
The main goal of the PET Aß scan should be to determine if a patient is eligible for Medicare coverage of an amyloid targeting drug that has FDA approval. While some suggest that repeated PET Aß scans are needed to track amyloid reduction over time, the more important measure is to track cognitive impairment over time. If a patient’s amyloid plaque is affected by the drug, as is expected, that is not evidence that their cognitive function was affected by the drug – and it is cognitive function that is the clinical outcome that is important to patients. Collection of data demonstrating improved cognitive function is the purpose of gathering information in the registry or in clinical trials.
Fortunately, cerebral metabolism measured by FDG-PET [a non-amyloid PET scan], and brain volumes measured by MRI are superior ways to evaluate the impact of these drugs on patients. MRI and ultrasound are the best way to evaluate ARIA and other adverse events that are essential for patients taking these drugs. There are also numerous studies in the published literature that suggest that FDG-PET is a superior tool for determining the effectiveness of Alzheimer’s therapies and for tracking disease advancement. For example, Khosravi et al. reported that “giving patients an amyloid PET scan is not an effective method for measuring their cognitive function,” whereas FDG-PET is “a better means for determining the effectiveness of Alzheimer’s therapies, as well as tracking patients’ disease advancement, in both clinical and research settings.”1,2
Therefore, we support expanding access to more than one PET Aß scan under very limited circumstances; for example, for patients who already had one PET Aß scan many months before needing a PET Aß to qualify for FDA-approved amyloid targeting Alzheimer’s treatments. It is essential that Medicare Administrative Contractors (MACs) consider the scientific evidence regarding the limited usefulness of PET Aß scans when making coverage determinations. We agree with the conclusion drawn by CMS in the previous PET NCD that “widespread clinical use of the scan [PET Aß] both in many types of patients with unexplained MCI, and to make a positive diagnosis of Alzheimer’s disease (despite insufficient evidence on the clinical meaning of a positive scan) has great potential to lead to over-diagnosis of Alzheimer’s disease.” That remains true today, since there are more likely to be false positive results with PET Aß compared to other Alzheimer’s diagnostic methods such as FDG-PET, as amyloid plaques may be present in many individuals with normal cognitive function or in mild cognitive function that is not caused by Alzheimer’s Disease. In fact, many people with amyloid plaques have no evidence of Alzheimer’s disease and may not develop it in the future.1
A recent 2023 study further challenged current diagnostic criteria for Alzheimer’s based on PET Aß imaging biomarkers and recommend that future therapies instead: (1) diagnose AD based on the co-occurrence of cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, and (2) determine efficacy by favorable effect on cognitive ability, cerebral metabolism by FDG-PET and brain volumes by MRI.[3]
CMS should take into account the research evidence and alternative testing options when making coverage decisions related to PET Aß scans. Despite pressure to increase access due to the approval of new Alzheimer’s treatments targeting amyloid, it is clear that the focus should be on evidence pertaining to cognitive function rather than evidence of changes in amyloid plaque, as well as evidence of the shortcomings of PET Aß scans compared to FDG-PET. When making determinations other than verifying that a patient qualifies for use of amyloid targeting treatments, MACs should take into account the evidence that a PET Aß scan provides less meaningful data than other tests to determine whether a treatment increases the likelihood of the clinical benefits that patients care about.
[1] Penn Medicine News. (2019). Measuring the brain’s amyloid buildup less effective in identifying severity, progression of Alzheimer’s disease compared to other imaging methods. https://www.pennmedicine.org/news/news-releases/2019/august/measuring-brains-amyloid-buildup-less-effective-alzehimers-disease-compared-imaging-methods
[2] Khosravi, M., Peter, J., Wintering, N. A., Serruya, M., Shamchi, S. P., Werner, T. J., Alavi, A., & Newberg, A. B. (2019). 18F-FDG Is a Superior Indicator of Cognitive Performance Compared to 18F-Florbetapir in Alzheimer’s Disease and Mild Cognitive Impairment Evaluation: A Global Quantitative Analysis. Journal of Alzheimer’s disease: JAD, 70(4), 1197–1207. https://doi.org/10.3233/JAD-190220
[3] Høilund-Carlsen, P. F., Revheim, M. E., Costa, T., Kepp, K. P., Castellani, R. J., Perry, G., Alavi, A., & Barrio, J. R. (2023). FDG-PET versus Amyloid-PET Imaging for Diagnosis and Response Evaluation in Alzheimer’s Disease: Benefits and Pitfalls. Diagnostics (Basel, Switzerland), 13(13), 2254. https://doi.org/10.3390/diagnostics13132254