The fallout from FDA’s findings of continued "significant deficiencies" that led to the suspension of brain-imaging studies at Columbia University’s imaging center is generating widespread condemnation from their academic peers in psychiatry nationwide.
Researchers in the field fear that these revelations–which, they acknowledge, is a "breach of a sacred trust," could damage public perception of clinical trials across the nation.
Below, The Associated Press and The Los Angeles Times report about the reaction to The New York Times revelations that FDA investigations found that Columbia University’s PET imaging center injected mental patients with impure radioactive tracers. Columbia’s denial notwithstanding, these corrupted studies put patients at risk of harm and undermined the integrity of the research.
The AP reports that:
Dr. Alexander Neumeister, a psychiatrist with the molecular imaging program at the Mount Sinai School of Medicine, said PET centers across the country routinely test tracers for sterility and purity just minutes before they are injected, while the patient is lying on the table.
The tests, he said, turn up impurities about 1 percent to 3 percent of the time, and make it nearly impossible to unknowingly inject adulterated medications.
"You’d have to be an idiot," Neumeister said, adding that he was speaking generally about the testing procedure, rather than the situation at the Kreitchman PET Center. "It’s like being pregnant — either you are, or you’re not; it’s very clear, there’s no gray zone, no ambiguity."
If an impure tracer is used, any resulting scientific studies "are compromised," Neumeister said. It also might affect a person’s health condition in unpredictable ways, like inducing allergies or worsening depression.
"It’s not that you’re killing a patient," he said, but, "you might be exposing your patient to various other levels of danger."
And Dr. Nancy C. Andreasen, a former editor-in-chief of the American Journal of Psychiatry, is quoted stating:
"If you’re approved by the FDA to administer compounds that pass purity tests, and then inject substances that do not meet quality assurance regulations, you are breaking a sacred trust."
The LA Times quotes Dr. E. Ray Dorsey, (University of Rochester): "It undermines the trust implicit between research participants and investigators."
AHRP is quoted noting that "Columbia is one of the major institutions in the field of psychiatric research both in terms of volume and money. These patients are exploited. They are voiceless."
And Dr. Gary Small, a professor of psychiatry and biobehavioral sciences at UCLA who does brain-imaging research focusing on Alzheimer’s diagnosis: Any slipshod work involving volunteers in clinical trials sends a shudder through the field. This is a problem because it’s very difficult to get people to volunteer for research"
Vera Hassner Sharav
ASSOCIATED PRESS
FDA cites quality problems at NY brain-imaging lab
By DAVID B. CARUSO and VERENA DOBNIK
Sat Jul 17, 2010NEW YORK – A respected brain-imaging center run by Columbia University has halted some research after federal officials repeatedly complained that patients were getting drugs that failed purity tests.
The Food and Drug Administration found in a series of inspections that the center had failed to correct manufacturing problems in a lab that makes experimental drugs injected into psychiatric patients to help capture images of brain activity.
In one warning letter, an FDA office in New York described problems dating back to at least 2004. It cited a litany of violations, including a failure to reject batches of medication that didn’t pass required tests. The drugs were for patients undergoing a type of brain scan called positron emission tomography, or PET.
"We are concerned about the quality control systems and procedural problems that have allowed these significant deficiencies to occur," the FDA told the center in the letter, written in December 2008.
In a statement sent Saturday to The Associated Press, Columbia University Medical Center said it was restructuring the laboratory that produces the drugs for the Kreitchman PET Center.
It said an internal investigation, performed at the FDA’s request, had found "no evidence of patient harm," but that all activities relying on the manufactured compounds had been suspended while reforms were undertaken.
"We acknowledge serious shortcomings of quality control in the manufacturing process and record keeping at this lab," said Dr. David Hirsh, the medical center’s executive vice president for research.
"That is why we are fundamentally reorganizing the lab’s management and operations in response to what the FDA told us. When manufacturing resumes under new leadership, it will meet the strictest standards and best practices for ensuring the quality of these materials," Hirsh said.
The problems at the imaging center and the halt in research were first reported late Friday by The New York Times.
The PET Center remains in operation during the shakeup, and patients continue to receive treatment, Columbia said.
The problems at the center involved radiotracing drugs injected into a patient’s brain to assist in capturing images used to study brain activity.
The drugs are not supposed to have any effect on the patient and they degrade quickly — so fast, in fact, that imaging centers must often manufacture them on the spot, rather than buy them from outside vendors.
The manufacturing process is strictly regulated by the FDA.
Dr. Alexander Neumeister, a psychiatrist with the molecular imaging program at the Mount Sinai School of Medicine, said PET centers across the country routinely test tracers for sterility and purity just minutes before they are injected, while the patient is lying on the table.
The tests, he said, turn up impurities about 1 percent to 3 percent of the time, and make it nearly impossible to unknowingly inject adulterated medications.
"You’d have to be an idiot," Neumeister said, adding that he was speaking generally about the testing procedure, rather than the situation at the Kreitchman PET Center. "It’s like being pregnant — either you are, or you’re not; it’s very clear, there’s no gray zone, no ambiguity."
If an impure tracer is used, any resulting scientific studies "are compromised," Neumeister said. It also might affect a person’s health condition in unpredictable ways, like inducing allergies or worsening depression.
"It’s not that you’re killing a patient," he said, but, "you might be exposing your patient to various other levels of danger."
Among the problems at Columbia cited by the FDA were a failure to set up appropriate sterility tests, poor record keeping and lapses in training.
"If you’re approved by the FDA to administer compounds that pass purity tests, and then inject substances that do not meet quality assurance regulations, you are breaking a sacred trust," said Dr. Nancy C. Andreasen, a former editor-in-chief of the American Journal of Psychiatry.
Andreasen, of the University of Iowa, an internationally known PET researcher, said the resulting studies are often used to determine dosages for treating patients in ordinary clinical settings. "And if a study is messed up, you could be overmedicating or undermedicating a patient," she said.
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THE LOS ANGELES TIMES
Safety violations at N.Y. brain lab may have bigger fallout
By Shari Roan, Los Angeles Times
July 18, 2010The suspension of some research at a prominent Columbia University brain-imaging lab because of sloppy practices could have repercussions beyond that laboratory, potentially affecting brain-imaging studies nationwide and raising questions about the safety of participants, research experts said Saturday.
The Kreitchman PET Center in Manhattan, part of Columbia University, halted brain-imaging studies after federal authorities reportedly found safety violations that could endanger patients and invalidate research findings. The center has admitted to poor manufacturing processes of radioactive compounds injected in patients and to sub-par record-keeping.
Columbia authorities reported the findings of its own internal investigation in a July 6 letter to the Food and Drug Administration. Lab personnel are alleged to have used chemicals that had failed required purity tests when conducting brain scans of people with mental disorders. The scans, called PET scans, produce images of the brain and various neurological processes.
The chemicals used at the Columbia center were found to have contained impurities at levels well above what is permitted under FDA protocols. The center has halted research using those locally manufactured chemicals; the lab itself remains open, is still conducting other types of research and continues to see patients.
Experts disagree on whether the Columbia incident is an anomaly or if such slip-ups are widespread in research labs. But the documented lapses highlight apparent disregard for patient safety that rarely comes to light at major research institutions.
No patients were harmed, according to a statement from Columbia University released Saturday. But the practices also include failure to report use of the substandard chemicals and even efforts to hide the shoddy work, according to a New York Times account. That article, in Saturday’s newspaper, first detailed the investigation and the resulting replacement of lab managers.
"We acknowledge serious shortcomings of quality control in the manufacturing process and record-keeping in this lab," Dr. David Hirsh, Columbia’s executive vice president for research, said in the university’s statement.
Experts familiar with such research say the suspension could damage public perception of clinical trials across the nation, deterring some people from enrolling in crucial studies and perhaps limiting — at least for a while — the potential advances gleaned from brain-imaging research.
"It undermines the trust implicit between research participants and investigators," said Dr. E. Ray Dorsey, an assistant professor of neurology at the University of Rochester Medical Center in New York, who has studied clinical trial participation.
Imaging studies have been key to helping brain researchers understand the biological basis for mental disorders, addiction and dementia — all while drug companies search for treatments for brain-based conditions.
"This area of research is one that is making great progress," Dorsey said. "And there is greater demand and fewer centers that do this type of research."
It’s particularly troubling that the violations at the Columbia lab occurred during research on people with serious mental illnesses, such as schizophrenia, said Vera Sharav, president of the Alliance for Human Research Protection, an organization in New York that works to ensure safe and ethical medical research practices.
The organization has complained repeatedly to Columbia University officials about protection of research participants in psychiatric studies, Sharav said.
"Columbia is one of the major institutions as far as psych research and in terms of volume and money," she said. "But these patients are exploited. They are voiceless."
Mentally ill patients may be particularly vulnerable. Federal guidelines designed to protect clinical trial participants include special instructions for groups such as pregnant women, prisoners and children, but there is no specific mention of people with mental illness, said Maureen Moran, an assistant professor of preventive medicine at Northwestern University, who teaches research ethics and serves on the board that oversees the school’s human subject research.
That’s not to say the abuses at the Columbia center were malicious. They probably were not, Moran said.
"The motivation is not so much ‘We don’t care about these people,’ as ‘Let’s just get this done,’ " she said.
Still, any slipshod work involving volunteers in clinical trials sends a shudder through the field, said Dr. Gary Small, a professor of psychiatry and biobehavioral sciences at UCLA who does brain-imaging research focusing on Alzheimer’s diagnosis.
"This is a problem because it’s very difficult to get people to volunteer for research," he said. "We are so grateful to those who do. Anything like this sort of incident makes it more difficult."
shari.roan@latimes.com
Copyright © 2010, The Los Angeles Times