An N.Y.U. Study Gone Wrong, and a Top Researcher Dismissed
By BENEDICT CAREY New York Times June 27, 2016
New York University’s medical school has quietly shut down eight studies at its prominent psychiatric research center and parted ways with a top researcher after discovering a series of violations in a study of an experimental, mind-altering drug.
A subsequent federal investigation found lax oversight of study participants, most of whom had serious mental issues. The Food and Drug Administration investigators also found that records had been falsified and researchers had failed to keep accurate case histories.
In one of the shuttered studies, people with a diagnosis of post-traumatic stress caused by childhood abuse took a relatively untested drug intended to mimic the effects of marijuana, to see if it relieved symptoms.
“I think their intent was good, and they were considerate to me,” said one of those subjects, Diane Ruffcorn, 40, of Seattle, who said she was sexually abused as a child. “But what concerned me, I was given this drug, and all these tests, and then it was goodbye, I was on my own. There was no follow-up.”
It’s a critical time for two important but still controversial areas of psychiatry: the search for a blood test or other biological sign of post-traumatic stress disorder, which has so far come up empty, and the use of recreational drugs like ecstasy and marijuana to treat it.
At least one trial of marijuana, and one using ecstasy, are in the works for traumatized veterans, and some psychiatrists and many patients see this work as having enormous promise to reshape and improve treatment for trauma. But obtaining approval to use the drugs in experiments is still politically sensitive. Doctors who have done studies with these drugs say that their uncertain effects on traumatic memory make close supervision during treatment essential.
The New York Times pieced together details of the research and the investigation through documents, letters and emails, as well as interviews with a participant and several researchers familiar with the project.
The violations “jeopardize subject safety and welfare, and raise concerns about the validity and integrity of the data collected at your site,” the F.D.A. said in a letter, obtained by The Times, to Dr. Alexander Neumeister, the studies’ lead investigator.
Dr. Charles Marmar, the chairman of the psychiatry department at N.Y.U., said that people working with Dr. Neumeister had reported concerns about the lab’s compliance with research standards. Once some of those issues were confirmed, Dr. Marmar said, the university placed Dr. Neumeister on leave, “and suspended all activity, suspended access to all accounts. I took control of those studies.” Dr. Neumeister later submitted his resignation.
Georges Lederman, a lawyer for Dr. Neumeister, said there may have been protocol violations, “but N.Y.U. has taken the position that those violations were more egregious than we believe they actually were.” The issues could have been easily remedied, he said, and noted that they did not cause the sponsor of the research, the pharmaceutical giant Pfizer, to shut it down.
Both the university and Mr. Lederman said there was no evidence that any study participant had been harmed.
Pfizer said that N.Y.U. was responsible for conducting the trial, and that the company had previously tested the same drug, known as an F.A.A.H. inhibitor, for osteoarthritic pain, without significant side effects. “The safety profile we observed does not preclude future development of our compound,” a Pfizer spokesman said by email.
Careful oversight is a centerpiece of ethical research practice, particularly when studies involve people taking an experimental drug. Earlier this year, six patients in a French trial of another experimental drug with similar, marijuana-like effects were hospitalized with severe neurological problems; one has reportedly died.
Study participants with mental disorders are especially susceptible to adverse reactions, experts said. “These are people who are more vulnerable to being exploited in the research process, and more vulnerable to things going wrong during the research, so you want extra vigilance,” said Elisa Hurley, the executive director of Public Responsibility in Medicine and Research, a national nonprofit devoted to promoting high research standards. “If someone in my family were in a situation like this, I would want to be sure that the institution was crossing its t’s and dotting its i’s.”
The study was an attempt to extend a small trial that Dr. Neumeister had done previously, suggesting that cannabis might relieve anxiety in some people with post-traumatic stress disorder. “We know very well that people with PTSD who use marijuana often experience more relief from their symptoms than they do from antidepressants and other psychiatric medications,” Dr. Neumeister said in a 2014 N.Y.U. news release after the first trial.
The research team decided to use a drug intended to produce some of marijuana’s effects, made by Pfizer, which financed the trial. Some participants took the drug over a seven-day period; others took a placebo pill. The N.Y.U. team performed scans on each person to see whether brain activation patterns correlated with symptom relief.
The study called for recruiting 50 people with a PTSD diagnosis, according to study documents. Only 14 enrolled at the N.Y.U. site, according to federal documents, and many had participated in previous studies by Dr. Neumeister. One had completed a study of another drug 16 days earlier, when the protocol called for a 30-day window, according to the F.D.A.
The federal inspection, from July 16 to Aug. 5 last year, found that the research team had failed to assess at least three subjects 24 hours after they had taken the experimental drug, contrary to study protocol, according to the F.D.A. letter. In several instances, the agency found, Dr. Neumeister had falsified documents by signing a fellow investigator’s name on reports. “However, in fact, you or another study employee actually conducted these study procedures,” not the colleague, the F.D.A. concluded.
Ms. Ruffcorn, who writes a popular Facebook blog on trauma called A Little Bent, said the most unsettling part of the experience was not the loose monitoring, but the preparations for the trial. To participate, the N.Y.U. team told her, she first had to stop taking all her medications. But the study had several false starts, requiring her to stop taking medication, then restart, then stop again — and restart.
“It was horrible,” she said. “I had flashbacks, returning nightmares, every symptom coming on full force, not to mention the withdrawal. After going off and back on four or five times, I told them, ‘I can’t do this anymore.’”
That’s when she was flown to New York to enter the trial.
Ms. Ruffcorn said she had several odd symptoms after the trial, including a hyper, wired sensation that occurred without the usual memories of abuse. For months, she tried to find out whether those reactions were tied to the experimental drug, but because the study was shut down and the data belonged to Pfizer, the N.Y.U. doctors could not tell her whether she’d taken the drug or a placebo.
Earlier this month, after much persistence, she found out that she’d taken the placebo. “It was a big relief,” she said.
Dr. Neumeister and N.Y.U. continue to disagree over the seriousness of the research violations, both sides said. But the university has tossed out all of the data as unreliable, and tracked down the study participants to check on their health, Dr. Marmar said.
“I honestly believed I had the best qualified and among the most ethical researchers on the faculty” running these studies, Dr. Marmar said.