Removing Amyloid NCD: Analysis

 Analysis section only, CMS removes NCD regarding amyloid PET scans.   AI summary found further below.

Introduction

NCDs are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§1869(f)(1)(B) of the Act). In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, and must not be otherwise excluded from coverage. Moreover, with limited exceptions, the expenses incurred for items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§1862(a)(1)(A) of the Act).

CMS is not required to establish an NCD.  The Supreme Court has recognized that “[t]he Secretary's decision as to whether a particular medical service is 'reasonable and necessary’ and the means by which she implements her decision, whether by promulgating a generally applicable rule or by allowing individual adjudication, are clearly discretionary decisions.” Heckler v. Ringer, 466 U.S. 602, 617 (1984). See also, Almy v. Sebelius, 679 F.3d 297, 303-04 (4th Cir. 2012) (“The Medicare statute preserves this discretion for the Secretary, leaving it to her judgment whether to proceed by implementing an NCD, by allowing regional contractors to adopt an LCD, or by deciding individual cases through the adjudicative process.”); International Rehabilitative Services Inc. v. Sebelius, 688 F.3d 994, 1001 (9th Cir. 2012) (“But while the agency may make coverage determinations via up-front rules, it is not required to do so; rather, the agency has discretion in whether to make coverage determinations by up-front rulemaking or by case-by-case adjudication.”)

The 2013 NCD for amyloid PET scans (220.6.20) notes that the available evidence suggested these scans were promising and therefore supported further research under §1862(a)(1)(E) of the Social Security Act (the Act) through CED. While there have been CED studies approved early when the NCD was established, there have been no CED study approved since 2016 (note: the New IDEAS study was a limited extension of the 2015 IDEAS study for underserved populations).  Based on published articles and conversations with stakeholders, we have been informed that a number of relevant clinical studies have been conducted and new evidence has been developed outside the context of the CMS CED, specifically for development of new treatments directed against amyloid (see CMS NCD 200.3 (at https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=305 )).  The research on amyloid PET has advanced and has been redirected towards antiamyloid treatments (e.g., Clarity AD trial) and the coverage of separate CED studies are no longer needed. With the new developments in medical care and treatments, the use of amyloid PET has changed and become important for patient selection for treatments.  Based on stakeholder feedback, we do not anticipate that any new CED protocols will be submitted for review under this NCD (we have not received any new protocol since January 2016).

For this NCD reconsideration, CMS initially focused on the following question:

• Should CMS revise the current policy of one PET Aβ scan per patient through CED?

In response to the comments received during the initial 30-day public comment period requesting that CMS remove the CED requirement from the NCD, as well as new evidence that became available, CMS is addressing the question below:

• Should CMS remove the current NCD for beta amyloid PET in dementia and neurodegenerative disease?

The clinical research is currently focused on new treatments directed against amyloid which require confirmation of the presence of brain amyloid pathology using tests such as amyloid PET.

NCD Removal

Since the establishment of the amyloid PET NCD in 2013, there have been a number of advances in medical care and treatments for AD.  For example, addressing certain health risk factors and comorbidities such as high blood pressure has been emphasized in overall treatment.  The 2020 Lancet Commission concludes that lifestyle changes and treatment of 12 modifiable risk factors associated with Alzheimer’s disease could potentially prevent or delay up to 40% of dementia cases (Livingston 2020).  Standards of care for patients with AD have also advanced.  For example, the American Academy of Neurology (AAN) recently published a review of the current evidence and clinical practice guidelines (Day et al., 2022).  The development of antiamyloid drug treatments such as monoclonal antibodies, laboratory-made proteins designed to bind a specific substance in the body with the goal of marking it for destruction by the body’s immune system, is particularly promising (CMS NCD 200.3, 2022; available at https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=375 .) 

The advances in medical care and standards of practice and development of proven treatments have altered the application of amyloid PET scans in clinical practice and research.  For example, promising antiamyloid drug treatments to improve health outcomes such as cognition and function would not be expected to have a clinical impact in the absence of brain amyloid.  Appropriate patient selection is key to ensuring benefits outweigh harms of newly developed drugs targeting amyloid.  By including useful diagnostic tests that can detect beta amyloid on the brain, harms of antiamyloid treatments would be avoided because the drug would not be given to patients that do not have brain amyloid and potentially stopped when brain amyloid was completely removed. When the 2013 CED questions were created, advances in the application of amyloid PET scans and the importance of patient selection for promising treatments were not known.  Currently, amyloid PET scans can be used to confirm presence of brain amyloid pathology to select appropriate patients for proven antiamyloid treatments depending on individual patient characteristics.  Advancements in antiamyloid treatments for AD are accelerating.  Isolated PET research separate from treatment trials through this CED NCD is no longer needed and no longer being requested by stakeholders.  Moreover, stakeholders and patients have specifically noted that the once-in-a-lifetime limit on amyloid PET is outdated and not clinically appropriate due to the development of antiamyloid treatments and the need to confirm the presence of amyloid to start these treatments and to possibly discontinue treatments when brain amyloid has been completely removed to avoid unnecessary treatment harms.

Recent treatment trials requiring biomarker evidence of amyloid pathology for patient enrollment generally have used PET Aꞵ brain scans.  The importance of this requirement is exemplified by early, failed solanezumab trials. An analysis of secondary outcomes reported that roughly 25% of trial participants did not have positive brain amyloid on PET scans and may never have had AD (Siemers 2016).  A treatment aimed at improving cognition and function for AD patients, precisely because it modifies underlying AD pathophysiology, is not likely to succeed if it is not AD from brain amyloid that is causing the patients’ symptoms in the first place.  Other types of treatments that are not classified as monoclonal antibodies are in accelerated development, as well, such as inhibitor drugs and nanotechnology.  These innovative treatments were not available in 2013 when the existing coverage criteria and limitation were established and would also need confirmation of the presence of brain amyloid for similar reasons.  We believe that allowing local MAC discretion to make a coverage decision for this diagnostic test better serves the needs of the Medicare program and its beneficiaries at this time.

Individual patient factors need to be considered for drug treatments such as the type and number of medical comorbidities a patient may have and the respective concomitant medication treatments. Certain medications such anticoagulants may affect the benefits and harms of certain antiamyloid drugs. In addition to the above, the use of amyloid PET would be dependent on the specific anti-amyloid treatment, individual patient response (amount of brain amyloid reduction), adverse events and corresponding need for subsequent testing to potentially stop treatments. For example, certain drugs may remove brain amyloid at different rates in different patients.  For patients that have brain amyloid reduced completely as shown on a test such as a PET scan, a physician and patient may consider the benefits and harms of certain drugs and whether discontinuation of treatment would be appropriate. 

The MACs may also take into consideration the local clinical environment and institutional factors in making coverage determinations. As one example, Grand and colleagues (2011) reported:

"The best approach to the care of individuals affected by dementia includes support from multiple sources. These may be integrated, parallel, or a combination of both.  It is ideal for patients and caregivers to seek a blend of multidisciplinary services that come from various healthcare providers, social service agencies, and professionals from outside the field of healthcare.  Multidisciplinary teams vary in their composition and may be structured either formally or informally.  Team construction is usually dictated by resources, including time, availability, finances, and geographic location.  Regardless of structure, successful teams are characterized by a shared commitment to quality care and an appreciation for the contributions of each team member.

Multidisciplinary teams involved in dementia care tend to be based primarily on the availability of service resources, in addition to the social and cultural context of the community.  Team members often include neurologists, geriatricians, neuropsychologists, nurse practitioners, physical/occupational therapists, nutritionists, and social workers."

We believe removal of NCD 220.6.20 will allow appropriate coverage of amyloid PET scans and will greatly reduce provider and patient burden from the existing requirements and test limitation. Stakeholders and patients have particularly emphasized the constraints on choice of treatments and appropriate management of proven antiamyloid treatments due to the once in a lifetime limitation.  As new treatments directed against amyloid for patients with AD, whether monoclonal antibodies, inhibitor drugs, nanotechnology or other new technology, are developed and approved by the FDA, the MACs are able to promptly respond to the evidence on proven treatments for individual patients.  CMS received 90 public comments to the proposed NCD. The large majority of commenters (86/90) supported ending of CED due to advancements in medical treatments since 2013.  Thus, for these reasons, we are removing the NCD for PET beta amyloid imaging, which would allow local MACs to make coverage determinations regarding the use of Aꞵ PET imaging, which may include covering more than one scan per patient’s lifetime and use within or outside the context of a CMS approved study.

New IDEAS CED study
Commenters informed us that the New IDEAS CED study is still active and has restarted full recruitment and enrollment. CMS appreciates the completed CED studies and the commitment by sponsors and investigators to continue evidence development.  The focus of New IDEAS on ethnoracially and clinically diverse Medicare participants is particularly important.  While the amyloid PET CED requirement will be ending, coverage of amyloid PET for Medicare patients with MCI due to AD or mild AD dementia will be determined by the MACs.

Health Disparities

Significant differences in the prevalence of AD across racial and ethnic groups have previously been reported.  Research has shown that AD is more prevalent in Blacks and Hispanics when compared to Whites, with Blacks being up to two times more likely to have AD and other dementias when compared to Whites, and Hispanics being about one and a half times more likely than Whites to have AD and other dementias (AA 2020, Mayeda 2016).  Despite the higher prevalence of AD and other dementias in Blacks and Hispanics, they are less likely to have a diagnosis when compared to Whites.  In a recent survey by the Alzheimer’s Association (2021), it was found that Black, Hispanic, and Native Americans were twice as likely than Whites to say they would not see a doctor if experiencing thinking or memory problems.  This can partially be explained by differing racial and ethnic beliefs about AD.  Significantly more Black and non-White Americans believe that symptoms of AD, such as significant memory loss, are part of the normal aging process when compared to White Americans (AA 2021, Connell 2009). This may also be partially due to higher rates of discrimination when seeking dementia-related health care. Recent surveys reveal that Blacks reported the highest level of discrimination in dementia health care (50%), followed by Native Americans (42%), Asians (34%), and Hispanics (33%), compared to Non-Hispanic Whites (9%) (AA 2021).

Additionally, under-representation of members of racial and ethnic groups in research relating to AD further exacerbates disparities in our understanding of, and ability to provide appropriate health care for, all individuals CMS serves related to these conditions.  Some barriers to the recruitment of under-represented patients can include language, logistical barriers (e.g., time, travel), and a long-standing mistrust of the medical establishment (Watson 2014).  In the same survey previously mentioned by the Alzheimer’s Association (2021), 62% of Black Americans believed that medical research is biased against people of color, and Black Americans expressed less interest in participating in clinical trials for AD than any other group surveyed (White and non-White).  Additionally, only 53% of Black Americans surveyed believed that a future cure for AD would be equally shared regardless of race and ethnicity. 

IX.   Conclusion

CMS is removing the NCD at § 220.6.20, ending CED for PET beta amyloid imaging and permitting Medicare coverage determinations for PET beta amyloid imaging to be made by MACs under § 1862(a)(1)(A) of the Act.

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AI SUMMARY (CHAT GPT 3.5)

The main reasons why CMS has decided to remove the national coverage determination (NCD) for beta amyloid Alzheimer PET scans are as follows:

• Advances in Medical Care and Treatments: There have been significant advances in medical care and treatments for Alzheimer's disease (AD), including lifestyle changes, risk factor management, and the development of antiamyloid drug treatments. These advancements have rendered the once-in-a-lifetime limit on amyloid PET scans outdated.
• Importance of Patient Selection: The development of antiamyloid drug treatments requires the confirmation of the presence of brain amyloid pathology, which can be achieved through amyloid PET scans. Ensuring that patients have brain amyloid is crucial to determining the benefits and avoiding potential harms of these treatments.
• Evolving Clinical Research: Clinical research is now focused on new treatments directed against amyloid, which necessitate the use of tests like amyloid PET scans to confirm brain amyloid pathology.
• Stakeholder and Patient Feedback: Stakeholders and patients have expressed concerns about the limitations on the choice of treatments and the appropriate management of antiamyloid treatments due to the once-in-a-lifetime limitation on amyloid PET scans.
• Local MAC Discretion: Allowing Medicare Administrative Contractors (MACs) to make coverage determinations for amyloid PET scans based on individual patient factors and local clinical environments is seen as more flexible and responsive to evolving medical care and treatment standards.
• Health Disparities: Recognizing health disparities in AD prevalence among racial and ethnic groups, CMS aims to address these disparities by allowing local MACs to determine coverage for amyloid PET scans for patients with Mild Cognitive Impairment (MCI) due to AD or mild AD dementia.

In summary, CMS is removing the NCD for beta amyloid PET scans due to advances in medical care, the importance of patient selection for treatment, evolving clinical research, stakeholder and patient feedback, the need for local MAC discretion, and the aim to address health disparities in AD diagnosis and treatment.