Healthy Skepticism Library item: 13454

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Publication type: news

Feuerstein A.
Elan and Wyeth Had Ties to Study's Authors
TheStreet.com 2008 Apr 7
http://www.thestreet.com/story/10410647/1/elan-and-wyeth-had-ties-to-studys-authors.html?partner=drugs

Full text:

An Alzheimer’s disease research paper published last year in a prestigious medical journal failed to disclose the financial ties one of the co-authors had to Elan and Wyeth as a paid consultant to the drugmakers.

The paper in the September 2007 Archives of Neurology, a journal published by the American Medical Association, describes the use of a new test — the neuropsychological test battery (NTB) — to measure the memory and mental status of patients with Alzheimer’s disease.

John Harrison, the consultant, was paid by Elan and Wyeth to create the NTB as a new cognitive test for the company’s experimental Alzheimer’s drug, bapineuzumab. As previously reported by TheStreet.com, Elan and Wyeth are seeking to convince regulators here and in Europe that the NTB should be used as the basis to approve bapineuzumab.

The NTB, the companies have argued, is a superior alternative to the ADAS-cog test, the most well-known and widely used measure of cognition in studies of mild to moderate Alzheimer’s patients today.

To help make their point, Elan and Wyeth have cited the Archives of Neurology paper, titled “A Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials,” as independent, scientific proof that validates the NTB.

Harrison is the lead author of that NTB paper, but his role as a consultant paid by Elan and Wyeth to create the test is not disclosed in it. Harrison is the only author of six listed in the paper’s conflict-of-interest statement as having no financial conflicts with Elan and Wyeth. Harrison’s five co-authors are all employed by Elan or Wyeth.

“The drafts of our manuscript specifically included reference to the fact that I had received payment from both Elan and Wyeth, though for some reason this disclosure does not appear in the published manuscript,” said Harrison in an email response to questions.

“This is clearly worthy of further investigation, and I will seek to discover why this statement was omitted,” he added.

Why Does Full Disclose Matter?
Studies have shown that when drug companies or an industry fund scientific research, the conclusions of that research tend to favor those who pay for it. This is why independent research is so highly valued and why, when drug companies are involved in the conduct or payment of research, proper financial disclosure is necessary.

One of the criticisms of Elan and Wyeth’s efforts to push the NTB as a new approval standard for Alzheimer’s drugs is that the two companies created the test specifically for use with their experimental drug bapineuzumab.

While the NTB is made up of component tests of memory and executive function that have been commonly used for years, the precise selection of certain tests, the omission of others and their compilation into a single battery with a specific statistical scoring system were all done with bapineuzumab in mind.

Elan and Wyeth, therefore, have financial involvement not only in developing a new Alzheimer’s drug, bapineuzumab, but also in the NTB test being used to evaluate bapineuzumab and in the research study published in the Archives of Neurology that purports to show that the NTB test is better than the ADAS-cog.

By comparison, the ADAS-cog test has been used successfully to get Alzheimer’s drugs approved, because it has been widely validated through years of independent research and use in clinical studies worldwide for a host of different drugs.

An Elan spokesman was asked to provide all independent research that validates the use of the NTB in Alzheimer’s clinical trials, especially since the NTB has never before been used as the basis to approve an Alzheimer’s drug.

The only research cited by the Elan spokesman, however, was the Archives of Neurology paper, which concludes, “The NTB … seems to be a reliable and sensitive measure of cognitive change in patients with mild to moderate Alzheimer disease. The psychometric properties of the NTB suggest that it may have particular utility in evaluating drug efficacy in clinical trials in which patients with mild Alzheimer disease are included.”

The authors of this paper, and that includes Harrison, all have financial ties to Elan and Wyeth.

Cindy Kuzma, spokesperson for JAMA/Archives, the publication arm of the American Medical Association, said the medical group was not aware of Harrison’s financial connection to Elan and Wyeth.

The Archives of Neurology’s author guidelines state that the medical journal’s “policy is one of complete disclosure of all relevant financial interests.” The journal requires all authors to “to report potential conflicts of interest, including specific financial interests relevant to the subject of their manuscript…”

Kuzma said JAMA/Archive editors, including JAMA editor-in-chief Catherine DeAngelis, would not comment publicly about the Harrison issue and said that a formal investigation into the matter could not be launched unless AMA/Archives received written documentation that Harrison was a paid consultant to Elan and Wyeth.

Last month JAMA was forced to publish a correction about another case of unreported financial disclosures in its pages involving authors of lung cancer research who failed to disclose patents and pending patents related to CT scans.

Another Alzheimer’s Test
Dr. Lon Schneider, an Alzheimer’s disease expert and a professor at the University of Southern California’s Keck School of Medicine, calls the omission of Harrison’s financial connection to Elan and Wyeth a “nitpicking detail” because “everyone knows that Elan and Wyeth paid for the study.”

Schneider believes that Elan and Wyeth are doing the right thing by trying to use the NTB as the test for their Alzheimer’s drug bapineuzumab. The NTB is probably a more sensitive measure of cognition than the ADAS-cog, he says, and regulators, including the U.S. Food and Drug Administration, will be open to its use.

Given the novelty of the NTB, however, Schneider did say that Alzheimer’s researchers will be more comfortable with bapineuzumab results from upcoming clinical trials that produce a positive signal on both the NTB and the ADAS-cog.

A positive result on the former but not the latter “would be a problem,” says Schneider, because the data would be hard to conclude that patients are receiving real clinical benefit from the drug.

Last week, Eli Lily & Co. (LLY – Cramer’s Take – Stockpickr) announced the start of a large phase III study of its Alzheimer’s drug, LY450139, which will use the ADAS-cog test as one of two co-primary endpoints.

Dr. Richard Mohs helped to invent the ADAS test in the late 1970s and early 1980s while working as a researcher and an expert in aging and Alzheimer’s at Mount Sinai School of Medicine and the VA Medical Center in New York. Today, Mohs works as a neuroscience researcher for Lilly and is helping to oversee the company’s LY450139 program.

“We chose to use the ADAS-cog for our cognitive primary endpoint because it has a long history of tracking the progress of disease in mild and moderate Alzheimer patients,” said Mohs. “There is a lot of information out there about it, and it’s the one instrument that is acceptable to all regulatory bodies.”

Did Lilly choose to use the ADAS-cog test over the NTB because Mohs was one of its co-inventors?

“My first priority is to do the best study that we can,” said Mohs. “If there was a good chance that something else was better than the ADAS-cog, we would be happy to use it.”