Alzheimer's experts are set to protest after Medicare issued draft guidelines last week saying it would only pay for an Eli Lilly and Co diagnostic test for the disease if patients were taking part in clinical trials for it.
Both Lilly and the Alzheimer's Association have released statements expressing disappointment with the decision by the U.S. Centers for Medicare & Medicaid Services (CMS), which cited "insufficient" evidence that the tests improve patient care.
The agency that runs Medicare did cite evidence that the tests may be of use to rule out Alzheimer's in certain difficult-to-diagnose cases and to help identify patients who would be good candidates for clinical trials seeking better treatments or prevention strategies for the disease.
Patient advocates and the company say the decision might slow the development of future diagnostic tests for Alzheimer's and deny patients with symptoms the chance to find out whether they have Alzheimer's or some other disease that causes symptoms of dementia.
Several experts admit there is still much to learn about what a positive scan might mean, and say CMS's decision to cover only scans used in clinical trials may help in the search for treatments for the fatal, brain-wasting disease that affects 5 million Americans and 38 million people worldwide.
HINDERING TIMELY DIAGNOSIS
Lilly's compound, known as Amyvid, has already been approved by the U.S. Food and Drug Administration, but Medicare reimbursement is seen as critical for the company because most people begin showing signs of dementia around age 65, the age when Medicare coverage kicks in.
"Restricting coverage could hinder a timely and accurate diagnosis," said Dr. Daniel Skovronsky, president and chief executive of Avid Radiopharmaceuticals Inc, a Lilly subsidiary, adding that "it may stifle future innovation."
In addition to Lilly, the draft guidance could affect a similar imaging agent being developed by General Electric Co's GE Healthcare called flutemetamol now under review by regulators in the United States and Europe. Both are radioactive tracers designed to light up deposits of an Alzheimer's-related protein called beta amyloid when used in conjunction with brain scans known as positron emission tomography, or PET.
Instead of agreeing to routinely pay for the $3,000 test, CMS proposed "Coverage with Evidence Development," a designation that suggests there are still gaps in the evidence over the benefits of the test. Using this designation allows the agency to gather more data by paying for scans in patients taking part in clinical trials. Once those are completed, CMS could use the data to render a decision on coverage.
"Essentially, they acknowledge that there is the possibly that coverage is important, but they don't understand it quite yet," said Maria Carrillo, vice president of medical and scientific Relations at the Alzheimer's Association, which strongly disagrees with the proposal. The decision is still subject to change before the final rule goes into effect in October.
Carrillo said prior to the decision, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging sent CMS a report detailing the limited circumstances under which the test would be appropriate, such as helping to rule out dementia caused by a condition known as frontotemporal dementia - which involves shrinking of the frontal and temporal lobes - or Alzheimer's disease.
She said she expects patients and the Alzheimer's research community to give CMS a lot of feedback on its draft document in the hopes of winning coverage in the final ruling, expected in October.
Lilly said it stands by its request for coverage of the tests in the appropriate patients.
WHAT DOES A POSITIVE SCAN MEAN?
Dr. Sam Gandy, associate director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York, said the decision walks a fine line between the strengths of the test and its weaknesses.
"I think CMS found a way to do something truly constructive while holding back what will undoubtedly be a tsunami of worried well who, if they had access to amyloid scans, would find that they have amyloid in their brains that is largely asymptomatic," he said.
"They would have no idea if or when their brains would begin to curdle in response to the amyloid, setting them on the road to dementia," Gandy said.
Gandy pointed to a recent study by Dr. Steven DeKosky of the University of Virginia and Dr. Oscar Lopez of the University of Pittsburgh, which suggested the tests were a poor predictor of whether people over 85 will develop Alzheimer's disease.
The study, which is ongoing, showed that more than half of cognitively normal individuals aged 85 and older who had beta amyloid deposits in their brains remained cognitively normal two years later.
Lilly, in its statement, says its test was not designed to predict whether Alzheimer's would develop, only to rule out Alzheimer's in patients with difficult diagnoses. A negative scan for the presence of beta amyloid would be a sign for doctors to look for other potential causes of dementia.
That still leaves the problem of what to tell patients who have a positive scan, said Dr. Ronald Petersen, an Alzheimer's expert at the Mayo Clinic in Minnesota.
In someone with a precursor condition to Alzheimer's known as mild cognitive impairment, or MCI, a positive scan may mean a higher risk of advancing to Alzheimer's more quickly than a negative scan would indicate, he said. "The data are accumulating, but I don't know if they are there yet," he added.
At Mayo, Petersen is conducting a study of thousands of cognitively normal people to try to answer the question, "What does a positive scan mean in a normal person who is 50, 60 and 70 years old?"
Currently no treatments can prevent Alzheimer's, but as companies work on new drugs, having tests that identify the disease will be essential, DeKosky said.
"One of the reasons for trying to do these studies now is to know what we will actually do once we have drugs that will make a difference," he said.