SNMMI/AA Draft Appropriate Use Criteria for Amyloid Imaging
Request for Comments: Deadline December 6th
The SNMMI/AA Amyloid Imaging Taskforce (AIT) is asking for comments on possible Appropriate Use Criteria (AUC) identified below regarding amyloid positron emission tomography (PET) imaging to determine in clinical practice the presence or absence of amyloid in the brain. The indications are broken out below into either appropriate or inappropriate use criteria. The taskforce recognized several elements common to all appropriate indications and set these apart with a separate Preamble. The Preamble is intended to characterize all patients for whom the appropriate indications apply, listed below as 1–3. Comments will be discussed by the AIT Committee for possible inclusion in the final document. The final published AUC may or may not be identical to the table below.
The Preamble substantially restricts the set of patients for whom amyloid imaging would be appropriate in several ways. First, an expert clinician who has specific training and experience in neurodegenerative disorders must evaluate the patient and determine that there is objective evidence of impairment. Second, the expert should evaluate all available clinical evidence, including the history, physical, neuropsychological and all available neuroimaging examinations in order to consider the possible causes of the illness as well as potentially confounding circumstances such as depression, medication effects, cerebrovascular, endocrine or other medical disorders. The expert clinician must conclude on the basis of all available evidence that 1) the cause of the impairment is uncertain and 2) AD dementia or its prodromal stage must be in the differential diagnosis. Finally, the expert must conclude that a determination of either amyloid positivity or amyloid negativity would both increase the level of diagnostic certainty and alter the plan for patient management.
Appropriate Use Criteria
Preamble: Amyloid imaging is appropriate in the situations listed below for individuals with all of the following characteristics: a) a cognitive complaint with objectively confirmed impairment; b) Alzheimer's disease as a possible diagnosis, but when the diagnosis is uncertain after a comprehensive evaluation by a dementia expert; and c) when knowledge of the presence or absence of amyloid-beta pathology is expected to increase diagnostic certainty and alter management.
Amyloid imaging is appropriate in the following situations:
1. Patients with persistent or progressive unexplained mild cognitive impairment
2. Patients satisfying core clinical criteria for possible Alzheimer's disease (i.e., atypical clinical course or etiologically mixed presentation)
3. Patients with progressive dementia and atypically early age of onset
Inappropriate Use Criteria
Amyloid imaging is inappropriate in the following situations:
4. Patients with core clinical criteria for probable Alzheimer's disease with typical age of onset
5. To determine dementia severity
6. Solely based on a positive family history of dementia or presence of ApoE4
7. Patients with a cognitive complaint that is unconfirmed on clinical examination
8. In lieu of genotyping for suspected autosomal mutation carriers
9. In asymptomatic individuals
10. Non-medical usage (e.g. legal, insurance coverage, or employment screening)
DISCLOSURE: The comments below do not reflect the views of the Society of Nuclear Medicine and Molecular Imaging
Name: Thomas Chaly
Comments: Dr. Wischik study from Cambridge indicate that both healthy brains and Alzheimers brains could be filled with amyloid plaque. According to him aggregated tau is responsible for the dementia. According to him amyloid is not what is making people demented. Most people at the age 50 and up will have amyloid plaque in their brain. Detecting amyloid by imaging over 50 years of age is a waste of Medicare funding. The amyloid imaging is not going to help any patient. First we have to establish the real cause for the formation of amyloid and the real cause for Alzheimer's disease. This amyloid imaging is useful only for pharmaceutical companies to make money and not to help a single patient. I I know I have amyloid in my brain, what is the next step. Please do not waste Medicare funding with amyloid imaging. Let the scientif community determine the real cause for Alzheimer's disease.
Name: James R. Crowley, CNMT
Comments: We need these types of powerful indicators - Alzheimer's is a terrifying and mysterious disease. A large study, such as a NOPR, project would be an excellent way to start this process. However, an obvious fact is all of these would be very long term studies. This type of imaging should be rolled out in a responsible manner and with evidence based medicine as the intent. I want access to this material and feel it is appropriate in our medical environment.
Name: Soo Borson MD
Comments: The proposed AUC are sufficiently broad to allow coverage of amyloid imaging for a large number of individuals. In general I think they are reasonable and will help to develop clinical experience with this new technology. I have three comments:
1. Criteria for "atypical" cognitive decline should be made more explicit.
2. The requirement that clinical management be altered by the results of amyloid imaging seems a bit premature, as we do not yet have compelling evidence that amyloid clearing agents are therapeutically useful nor do we have any evidence that available antidementia medications depend on amyloid status for their effects.
3. The criteria do not speak to existing ethnocultural and socioeconomic biases in diagnosis, subtyping, and access to thoughtful management of dementia, and, if approved for coverage, use of amyloid imaging may exaggerate rather than mitigate these sources of health care disparities. This is a much larger issue, of course, but one worth noting.
Name: Ivalina Hristova
Comments: Questionable appropriateness - used to assess therapy efficacy for patients with positive Amyloid test.
Name: Ivan E. Diaz Meneses, MD
Comments: There are some longitudinal clinical trials that report the ability of amyloid imaging to identify individuals at higher risk to develop mild cognitive impairment or dementia, is there any place for an indication with predictive or prognostic purpose in the future?
Comments: I agree with 3 conditions necessary for amyloid imaging in clinical practice (excluded research):
- appropriate use criteria
- other exams do not help for diagnosis of AD (MRI, neuropsychological tests, perfusion SPET or TEP FDG),
- necessity of diagnosis for appropriate medical cares
Name: Xiong HAN, MD
Comments: Dr.Thomas Chaly have said the true that both healthy brains and Alzheimers brains could be filled with amyloid plaque. However,we could do something to establish the real cause for Alzheimer's disease,and amyloid imaging may be a tool and so I support this guidline and want it to be rolled out in a responsible manner, then give us some reliable evidence.
Name: Michael Rothman MD
Comments: Neuroradiologist agrees with APPROPRIATE & INAPPROPRIATE indications/policy.
Name: Brian Abraham (MITA)
Comments: As the leading trade association representing medical imaging manufacturers, the Medical Imaging & Technology Alliance (MITA) has an in-depth understanding of the patient benefits that medical imaging, including the use of radiopharmaceuticals, provides. MITA appreciates the effort by SNMMI and AA via your Task Force on Appropriate Use of Human Amyloid Imaging. We thank the Amyloid Imaging Taskforce (AIT) for soliciting comments on potential appropriate use criteria (AUC) for beta amyloid positron emission tomography (PET) imaging in the detection of amyloid in the brain. We hope the AIT will be amenable to modifications of these criteria as warranted. MITA would welcome meetings with the AIT at any time to gain a greater mutual understanding of this work so that the collective perspective of our members is included as part of the consideration of the criteria.
The AIT mentions in the description of the Preamble that “an expert clinician who has specific training in neurodegenerative disorders” would evaluate the patient to determine appropriateness for the imaging procedure; in the actual Preamble, there is mention of a “dementia expert.” We would like to have clarity on (a) whether these “experts” are the same diagnosing physician; (b) assuming they are the same physician, what the qualifications of these experts are, considering that many primary care physicians with extensive training and experience, but perhaps not a specialization in dementia or neurodegenerative disorders, are often the ones diagnosing dementia/neurodegenerative disorders. We would hope that a patient is not forced to see a specialist who may have no more experience or training than the patient’s primary care physician simply to receive a necessary scan that meets the proposed criteria in every other way.
We fear that this requirement could create a patient access issue as the number of specialists in this area may not be enough to fill demand as the population ages. For example, there may not be a specialist meeting the above criteria within a certain geographic area, potentially adding undue hardship on patients by forcing them to travel great distances to see such a specialist.
The description of the Preamble also lists the types of clinical evidence that the “expert” should evaluate in judging whether the patient is eligible for the beta amyloid scan. While there is mention of all “available” evidence, we hope that if a piece of evidence listed in this descriptive paragraph is not available (e.g., a neuroimaging examination), that absence would not presumptively exclude the patient from receiving a scan.
In the concluding sentence of the description of the Preamble, as well as in the final phrase of the Preamble itself, the AIT states that both increased diagnostic certainty and altered patient management would result from performing the beta amyloid scan. There are circumstances, though, that increased diagnostic certainty confirms the physician’s intent to treat the patient in a certain manner, and thus both conditions here would not be met. We respectfully suggest that there not be an expectation that patient management would de facto be altered by utilizing the imaging procedure.
Regarding the appropriate and inappropriate situations for this imaging procedure, we again agree in principle with the criteria. We believe, though, that further clarification of the following items would promote a greater understanding of the optimal use of the procedure.
1. MITA agrees that it is appropriate to perform a beta amyloid PET imaging procedure on patients with persistent or progressive unexplained mild cognitive impairment (MCI). We seek greater definition, though, on how the AIT defines the terms “persistent” and “progressive.” For instance, when a patient at a certain age presents with a persistent symptom or complaint, is there a specific time frame that patient must continue to present with that symptom or complaint? Similarly, how far does a condition have to progress before it is appropriate for the patient to receive a scan? We also would like to know whether these terms would be subjectively determined by the physician.
2. MITA conditionally agrees that is appropriate to perform this procedure for patients satisfying core clinical criteria for possible Alzheimer’s Disease. However, we again would like to have the AIT clarify from where the core clinical criteria are derived.
If these criteria come from those delineated by the National Institute on Aging (NIA), then we are in complete agreement. If the criteria are from a different source, we would have to review that source before committing to full support of the referenced core clinical criteria.
3. Again, without a more complete definition of the term ‘progressive’, MITA can only conditionally agree that patients with progressive dementia and atypically early age of onset should receive the scan. We also desire further clarification on when an “early age” of onset is atypical, whether due to family history or other circumstances.
4. MITA agrees that it would not be appropriate to perform a beta amyloid PET scan for a patient with probable Alzheimer’s Disease with typical age of onset. However, we would want to ensure that the diagnostic certainty on this probability is definitively high.
Thus, if there is not diagnostic certainty on the probability, then we do not believe it is inappropriate for a patient to receive a scan, and the patient likely will fall into one of the three appropriate situations mentioned.
5-10. MITA agrees that each of the remaining inappropriate situations, on their own, do not warrant a patient receiving a beta amyloid PET scan.
MITA suggests the addition of monitoring of therapy as an inappropriate situation. Although this may seem to be included in “determining the severity of dementia,” it warrants a separate discussion. Determining the severity of dementia could be performed with one scan to indicate the burden of amyloid plaque on the brain. Monitoring therapy, on the other hand, would occur after a patient received a “baseline” scan indicating the existence of Alzheimer’s Disease, was subsequently placed on a therapeutic regimen, and then received a repeat scan to determine whether the plaque level remained the same or was different.
Given the lack of therapies that reduce amyloid plaque, and the current test is a visual binary read, this type of use would not be appropriate at this time.
MITA also asks that these criteria be reviewed periodically, either at specified intervals or as new clinical use of the procedure evolves.
Again, MITA appreciates this opportunity to comment on the appropriate use criteria for beta amyloid imaging, and we welcome any questions you may have. To contact us, please email Brian Abraham, Sr. Policy Director, email@example.com or dial (703) 841-3258.
Gail M. Rodriguez, PhD
Executive Director and Vice President, NEMA
Name: David B. Pendleton
Comments: Navidea Biopharmaceuticals supports the AUC initiative and appreciates the opportunity to comment.
- AUC must be periodically revised, particularly as advances in therapeutics, diagnostics and evidence are anticipated
- Consider adding Uncertain category for applications with evolving evidence
- Similar to other AUC, a statement should be included acknowledging circumstances in which a test may be valuable in a particular patient while not meeting AUC
- “core clinical criteria for possible/probable AD” should be derived from NIA
- Limitation to referral from a “dementia expert” could restrict appropriate care, and may be a redundant limitation given the other AUC
- How is “dementia expert” defined?
- How are “persistent”, “progressive”, “early age of onset” defined? There should not be an expectation of change in patient management in each case, particularly in circumstances when the test is confirmatory
-Agree that test is not appropriate for patients with probable AD with typical age of onset, but diagnostic certainty of “probable” should be high
We agree with inappropriate criteria #5-10