Findings on Alzheimer’s Drug Challenged : FDA Questions Doctor’s Methods, Claims of Dramatic Improvement
In findings that raise serious allegations of scientific fraud, the U.S. Food and Drug Administration has challenged an Arcadia psychiatrist’s widely publicized claims that an experimental drug sometimes causes “dramatic” improvements in patients with Alzheimer’s disease.
The psychiatrist, Dr. William K. Summers, is being asked to respond to the allegations by the agency, which is considering whether to disqualify him from testing new drugs.
The FDA’s findings call into question a 1986 New England Journal of Medicine article, of which Summers was principal author, on the highly touted drug THA, or tetrahydroaminoacridine, which is now being evaluated in a national study of 300 Alzheimer’s patients.
“There are numerous statements in your (Journal) article that appear to be false,” Dr. Frances O. Kelsey, director of the FDA’s Division of Scientific Investigations, said in a six-page letter to the physician, a copy of which was obtained by The Times on Friday.
For example, the detailed FDA review failed to verify claims that some patients disabled by Alzheimer’s disease and then treated with THA were able to resume a variety of activities of daily life, including one who reportedly resumed his golf game.
“In a review of your study records, we were unable to identify the three subjects you claimed were able to resume homemaking, employment and golfing, i.e., those who had dramatic, meaningful improvement,” Kelsey wrote in her Jan. 19 letter.
The FDA audit also turned up numerous alleged examples of missing and altered data, biased research methods, failures to protect the rights of research subjects and other inadequacies, according to the letter.
Other Illnesses, Other Medications
There were instances where patients had other illnesses, in addition to Alzheimer’s, or were on other medications, in addition to THA. This may have confused the results, the FDA said.
In one case, Kelsey said Summers had concealed the fact that 10 of the 12 patients in one phase of the study lived more than 2,000 miles from his office. “Medical monitoring was erratic and conducted mainly through telephone contacts and letters with either family members who had a variety of perceptions or local physicians who, you concede, often did not follow your research protocol,” the letter said.
Summers declined to be interviewed Friday. But through a spokeswoman he released a copy of two recent letters sent to patients in the studies and to what the spokeswoman described as “supporters” of his research.
“I do not agree with the FDA accusations,” Summers wrote. He also accused the FDA of offering him choices “characteristic of a tyrant accustomed to abusing power” and attempting to achieve “a long-term hidden goal” of ending his project.
“What do I do?” he wrote. “Do I betray my research and my believe (sic) in its validity and sign their ‘true confession?’ Do I bankrupt myself in legal fees?”
In an interview with The Times last month, Summer downplayed the significance of the FDA probe. “We stand by our findings,” he said.
Summers is now being given an opportunity to respond in writing or in person to the FDA’s allegations, before the agency reaches a final decision on whether to stop him from testing new drugs or to take other actions.
An FDA spokesman said the ongoing investigation will have no immediate effect on Summers’ authorization to continue testing THA on about 40 Alzheimer’s patients. It also does not affect the separate national study of THA, which is being coordinated by Warner-Lambert Co., a Morris Plains, N.J., pharmaceutical company that makes the drug.
The ability of THA to benefit Alzheimer’s patients remains “a credible hypothesis to test,” said Dr. Paul Leber, the director of the FDA’s division of neuropharmacological drug products.
“My personal judgment is that it will not cure dementia,” Leber said in a telephone interview from Rockville, Md. “My guess is that it will have a modest symptomatic effect in some patients.”
The FDA’s allegations of scientific misconduct are the latest in a series of controversial episodes surrounding Summers and THA.
After the initial New England Journal report in November, 1986, that THA had markedly improved the memory and living skills of about a dozen Alzheimer’s patients for a year or more, patients, family members and physicians bombarded researchers and the government with requests for the medicine.
But in 1987, the bubble of favorable publicity seemed to burst. The New England Journal published six letters sharply critical of Summers’ methodology and the FDA began its audit. In addition, there was increasing criticism of the fact that Summers asked some of the patients and their families to pay the costs of the experimental treatment, which ranged up to $12,000 a year.
The two-year national study of THA, funded by Warner-Lambert, the National Institute of Aging and the private Alzheimer’s Disease and Related Disorders Assn., also experienced troubles. It was stopped in October, weeks after it was started, following the development of abnormal “liver function” blood test results in eight of about 35 patients who received high doses of THA.
The study is being resumed this month, with lower doses of medicine and stricter monitoring procedures to assure patient safety.