This story never clearly explained what information is conveyed by a positive or negative test and how the result might be useful for decision-making in patients with cognitive impairment.
This story describes the FDA approval of a new agent, called Amyvid, that is used together with PET scanning to detect amyloid plaques in the brain. Although the headline suggests that the test will “aid early diagnosis” of Alzheimer’s, the story never explained to readers that a positive test is not an accurate indicator of Alzheimer’s disease. As the FDA pointed out in a statement, “a positive Amyvid scan does not establish a diagnosis of AD because, although patients with AD always have an increased brain content of plaque, the test also may be positive in patients with other types of neurologic conditions, as well as in older people with normal cognition.” It appears that the test is useful primarily to help rule out Alzheimer’s disease in patients who don’t have the condition, since “a negative Amyvid scan indicates few to no neuritic plaques and reduces the likelihood that any cognitive impairment is due to AD,” according to the FDA. This basic, yet critical information should have been the foundation for the story, but somehow escaped mention.
As we’ve seen time and again with tests such as PSA, mammography, and coronary calcium, the information provided by scans and screens creates incentives to take action that may be unnecessary or counterproductive. It is reasonable to fear that we are on the same path with Amyvid, which tells us who has plaques in the brain but can’t tell us what disease they have or whether they are even destined to develop full-blown dementia. Having a rational discussion about the use of this test requires understanding what it can and cannot tell us about someone’s risk of developing Alzheimer’s disease–and that requires solid health reporting.
The story calls the test “costly” but does not quantify it. The cost of the agent itself, the associated PET scanning, and the interpretation of the test are not mentioned. The story does state that the test is not covered by Medicare or major insurers at this time, but readers have no idea what they would be on the hook for if they decide to pay for the test out of pocket.
The story is not careful enough in its description of what information the test provides and how it should be interpreted. The story states that the test “is an early test for those who already have cognitive concerns and who wonder whether Alzheimer’s disease may be the cause.” The implication is that the test can distinguish Alzheimer’s disease from other forms of dementia in people with cognitive impairment, which is not true.
As manufacturer Eli Lilly makes clear in its statement about the FDA approval, a negative scan indicates the absence of amyloid plaques and suggests that the cognitive impairment is probably not due to Alzheimer’s. However, amyloid plaques are found in patients with many other neurologic conditions and in patients with normal cognition. Thus, a positive scan cannot tell us if the patient has Alzheimer’s disease or some other cognitive problem or even if they are destined to develop dementia.
The story hints at the potential harm of receiving a positive test result at a time when there are no effective treatment options for Alzheimer’s. However, harms were not addressed directly enough to merit a satisfactory rating, in our opinion. As with any diagnostic test, this test may cause harm from a false-positive result, which may create unnecessary anxiety, or a false-negative reading, which may create a false sense of security and delay appropriate management steps. The test is also radioactive and contributes to the patient’s lifetime radiation exposure and cancer risk. None of these downsides is discussed in the story.
Since the test was approved by the FDA, the reader can assume that the supporting research meets a high standard for clinical evidence. We’ll award a satisfactory on that basis, but we think a more complete account would have referred to the fact that this test was initially rejected by the FDA over concerns that the scans would not be accurately interpreted without appropriate training. We also would like to have seen some acknowledgment of the fact that there are dissenting experts who feel the technology is not ready for FDA approval, as discussed in this Pharmalot post and this series in the UPenn student newspaper. (Much of the initial research for this test was conducted by UPenn researchers.)
The story quotes an expert source, Dr. Michael Weiner, who was involved in the development of Amyvid, but it does not mention that he has disclosed relationships with a number of pharmaceutical companies, including Eli Lilly, Amyvid’s manufacturer. In addition, the story mentions that Weiner is the leading researcher on the Alzheimer’s Disease Neuroimaging Initiative, but does not disclose that this consortium is partially funded by industry.
Since the drug had previously been rejected by the FDA’s scientific advisory committee, a dissenting voice would not have been hard to find.
The story mentions the existence of at least one similar agent that is being tested as a diagnostic aid. Other approaches, such as testing for biomarkers of Alzheimer’s disease in spinal fluid, are also in the works.
The product’s approval by the FDA does not mean that testing will be widely accessible in the near future. The statement from Eli Lilly explains why: “Because Amyvid loses over half of its radioactivity every two hours, Amyvid must be distributed directly from a radiopharmacy to the imaging centers where it will be administered within several hours. Beginning in June, a limited number of radiopharmacies will be distributing Amyvid with the goal of making the product available in more areas as soon as possible.”
The story does not overstate the novelty of the test or its approval by the FDA.
To our knowledge, the story did not rely on a press release.