Your health insurance may not cover brain amyloid scans anytime soon. Yesterday a committee convened by the Centers for Medicare & Medicaid Services (CMS) met to judge the evidence that β amyloid scans improve a patient’s health. Panel members found hard data wanting, ruling that too little evidence exists to answer this question. On a scale of 1 to 5, with 5 indicating strong confidence in the data, the committee voted a 2.17 in aggregate, below the threshold of 2.5 that was necessary for the committee to even vote on three of the remaining five questions before it. Besides lack of data, the committee worried about possible misuse of the technology. “I’m afraid this test is going to be equated with a diagnosis of AD,” one member said.

The committee’s vote will help inform the agency’s coverage decision, which is expected in July 2013. Much like the Food and Drug Administration, the CMS usually, but not always, follows the recommendation of its expert committees. Private payers tend to follow the CMS' lead. If the CMS rules against coverage, the decision will likely limit clinical use of amyloid scans, as their price tag of $3,000 to $6,000 apiece puts them beyond reach of many people.

Amyloid scans have been used in research for almost a decade, but the technology only became clinically available in April 2012, when the FDA approved the first β amyloid imaging agent, Eli Lilly’s Amyvid® (see ARF related news story). The CMS currently excludes coverage for all new positron emission tomography (PET) tracers, including Amyvid (see ARF related news story). In October 2012, Lilly petitioned the agency to consider coverage of β amyloid imaging agents for the diagnosis of dementia (see ARF related news story). In response, the CMS opened a National Coverage Analysis of the issue, and assembled the 13-member Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to hear the evidence. The panel, composed of independent clinicians and healthcare professionals, regularly advises the CMS on coverage decisions.

At an all-day meeting in Baltimore, Maryland, the MEDCAC heard presentations from AD clinicians and researchers about the role of amyloid imaging in diagnosis. William Thies of the Alzheimer’s Association discussed newly published Appropriate Use Criteria (AUC) developed by the Amyloid Imaging Task Force (see ARF related news story). These criteria recommend limiting scans to certain specific populations, such as people with measurable mild cognitive deficits or atypical presentations. Thies suggested covering scans for only those people who meet the appropriate use guidelines. Numerous other speakers agreed, with clinicians and representatives of imaging societies alike expressing broad support for adopting the AUC. Speaking for Lilly, Mark Mintun noted that the criteria in effect operationalize the FDA’s label indications for Amyvid.

What the committee most wanted to hear about, however, was patient outcomes. In impassioned, at times emotional, testimony, clinicians shared anecdotes about how the results of an amyloid scan changed the diagnosis, treatment plans, and life decisions for individual patients. For example, neurologist Carl Sadowsky at Florida’s Nova South Eastern University in Fort Lauderdale, described a 72-year-old doctor diagnosed with mild cognitive impairment (MCI) who had stopped working. His negative amyloid scan showed that his risk of progressing to AD was low. The man was “dramatically reassured” and returned to work, Sadowsky said. On the other side of the coin, a 69-year-old executive with MCI reacted to his positive amyloid scan by putting his financial plans in order and enrolling in a clinical trial of an amyloid-lowering drug, Sadowsky said. Lou Bordisso has a diagnosis of early AD and volunteers for the Alzheimer’s Association. Bordisso said that when he became ill at the age of 57, his doctors initially had difficulty diagnosing him. He felt anxious and confused. Not knowing his prognosis, he delayed applying for Social Security disability and Medicare benefits. His positive amyloid scan allowed him to engage support services and get on with his life, he said. “This technology replaces doubt with certainty.”

However, one MEDCAC member noted that the preponderance of anecdotal data “made him nervous.” Mintun provided the only dollop of hard data, describing a Lilly-funded study finding that use of amyloid scans changed the diagnosis in uncertain cases about half the time (see Grundman et al., 2013). Steven Pearson, who heads the independent academic research group The Institute for Clinical and Economic Review (ICER), noted that the Lilly study represents the only published results to date on whether amyloid scans actually alter diagnoses, and no studies examine longer-term patient outcomes as yet (see ARF related news story). Some studies are ongoing. For example, Gil Rabinovici at the University of California, San Francisco, is examining records from 140 patients at a memory center to see if amyloid scan data changed the diagnosis or medication the patients received (see ARF related news story). Committee members expressed frustration with the dearth of hard data. They asked for more outcome studies, especially those focused on people with MCI, who might be most likely to receive amyloid scans.

Several panel members acknowledged that the technology holds potential value for patients. They suggested that amyloid imaging might lend itself to a “coverage with evidence development” (CED) process such as CMS used with oncology ligands. In this approach, amyloid scans would be covered for Medicare beneficiaries as long as their doctors submitted data about health outcomes to CMS. Once a large body of data demonstrated patient benefits, the technology could gain full coverage.

Several panel members expressed concern about the potential for misuse of the test. Committee chair Rita Redberg, a cardiology professor at the University of California, San Francisco, and editor of the Archives of Internal Medicine, pointed out that many of her elderly patients complain of memory problems when they see her for heart ailments. Will large numbers of people start requesting amyloid scanning? Since 30 percent of cognitively healthy elderly people have brain amyloid, widespread testing has the potential to do more harm than good, the committee suggested. Although the appropriate use criteria recommend scanning only people with measurable cognitive deficits, the committee wondered whether this would be enough to safeguard patients in clinical practice throughout the country. “I applaud the appropriate use criteria, but I wonder how they are going to be enforced,” said Raymond Faught, a clinical neurologist at Emory University in Atlanta, Georgia.

In addition to Faught and Redberg, the MEDCAC included one other neurologist, a neurosurgeon, two psychiatrists, two psychologists, a radiologist, a general practitioner, an internist, and two health outcomes analysts. In addition, three guest panel members sat in to provide specific expertise, but their votes did not count toward the final score. They included an industry representative, a PET radiologist, and a psychiatrist specializing in AD. Incidentally, the guest panelists voted higher than the bona fide committee members whose specialties lie outside of AD.

Reached for comment by Alzforum, Mintun said he was pleased that the AD community expressed strong support for amyloid scanning at the meeting. “Presenter after presenter described a need for better diagnostic ability, and said there are people who would benefit from this,” Mintun said. He was not enthusiastic about the possibility of a CED process for Amyvid, noting, “We believe that for certain people, coverage would be useful right now, and additional research is not necessary.” Mintun said Lilly remains committed to working with CMS to get Amyvid coverage approved. Lilly is conducting a Phase 4 trial to gather more outcome data.

Norman Foster at the University of Utah, Salt Lake City, who spoke at the meeting, expressed disappointment with the committee’s vote. “It is unfortunate that my patients will continue to be refused this medically necessary procedure,” he told Alzforum. “I think the field as a whole was surprised by the result of the meeting.” He does not support a CED process for amyloid scanning, because CMS does not have clear rules for how CED should be used and how much evidence is enough to end CED, he added. Foster recommends that physicians and advocacy groups put pressure on insurers to cover amyloid scanning for those patients who need it. Foster sat on the task force that developed the appropriate use criteria.

The MEDCAC’s recommendations now go to CMS to aid the agency in its coverage deliberations. Louis Jacques, who directs CMS’ Coverage and Analysis Group, noted that the agency will continue to consider other evidence and newly published studies as they prepare their decision.––Madolyn Bowman Rogers.

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  1. CMS declined coverage recommendation because there is no evidence that amyloid PET scan results have any impact on outcome.

    We might need a new strategy for Amyvid® coverage. We may not be able to show that intervening therapeutically at the age covered by Medicare will lead to a clinical benefit. The field has redefined AD as a middle-age disease with clinical manifestations not appearing until after the age of 65 years old. If amyloid deposition begins between age 40 and 50, then those are the people whom we will want to target for therapeutic intervention that will hopefully be meaningful.

    But there is a problem here. The healthcare payers who take care of us in midlife are not focused on what happens after age 65, yet if we are to improve outcome, we must persuade third-party payers to cover Amyvid scans for people who will age beyond the window covered by those payers before the disease becomes clinically evident. Will the third-party payers see much incentive to pay for $4,000 scans for each person if Medicare has the liability for that older age group and will realize the benefit of the midlife evaluation with amyloid PET?

    In other words, because of the age-specific insurer system in the U.S., one can envision a scenario in which neither third parties nor Medicare will pay for Amyvid.

    Another issue that did not come up is whether any payer, CMS or private third party, will accept divergence of biomarker slope as a therapeutic benefit gained with treatment following a presymptomatic Amyvid scan, or if they will require a meaningful clinical benefit as an outcome. There has been attention on whether the FDA would accept biomarker slope divergence, but that is only the first step. After approval, someone must pay. Based on Wednesday's discussions, I would speculate that this CMS panel would not accept biomarker divergence alone, and would insist on a meaningful clinical benefit. A tall order.

  2. I think the average MEDCAC vote represents a reasonable interpretation of the current state of the evidence, with the fact that studies have not yet been done to evaluate the impact of using the test results on actual clinical decision-making or patient outcomes. My opinion on needed future studies mirrors the recommendations in our white paper. In the current era of treatments with only limited effectiveness, I think payers will require RCTs of diagnostic tests. I do think that studies which measure impact on clinical decision-making may offer evidence that can be linked strongly enough to patient outcomes, but again, with the current
    therapeutic armamentarium it will be challenging to find changes in clinical decisions that are substantive enough to provide confidence that they lead to significant changes in patient outcomes. All these considerations will transform overnight if a trial using PET amyloid—or other biomarkers—to enroll patients shows a substantial clinical benefit. May we be so lucky as to face that situation soon!

References

News Citations

  1. FDA Approves Amyvid for Clinical Use
  2. HAI—Amyloid Imaging in the Clinic: New Guidelines and Data

Paper Citations

  1. . Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Alzheimer Dis Assoc Disord. 2013 Jan;27(1):4-15. PubMed.

Other Citations

  1. ARF related news story

External Citations

  1. Centers for Medicare & Medicaid Services
  2. National Coverage Analysis
  3. meeting
  4. The Institute for Clinical and Economic Review
  5. Phase 4 trial

Further Reading