Drug Trial Scandal at N.Y.U.? What We Know

By Neuroskeptic | June 29, 2016 1:54 am

The New York Times breaks the story of an ostensibly serious case of misconduct at New York University (NYU):

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…

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.

So what’s going on, and how serious is it? The NYT piece is rather light on detail. For instance, it doesn’t name the “mind-altering” drug used in the problematic study, only saying it is an experimental FAAH inhibitor produced by drug company Pfizer.

I believe the compound in question is PF-04457845.

PF-04457845_structureI believe this because ClinicalTrials.gov lists a trial of PF-04457845 for PTSD, a trial which was recently terminated. NYU was one of the research sites. I also think that this trial is the fateful one, as it matches the NYT’s description of that study. Interestingly, ClinicalTrials.gov says that the trial was stopped “based on Pfizer portfolio prioritization and not due to safety and/or efficacy concern or change in benefit:risk assessment of PF-04457845”.

FAAH inhibitors such as PF-04457845 work by inhibiting the breakdown of endocannabinoids, neurotransmitters in the brain with cannabis-like properties. The best-known drug of this class is probably BIA 10,2474, the compound that led to severe adverse events including one fatality in an ill-fated French trial earlier this year. There’s no evidence that PF-04457845 shares similar risks, however.

As to the other NYU studies which were “shut down” as a result of this affair, the NYT gives no details. It’s not clear whether those studies were stopped because they had identifiable problems of their own, or as a precautionary measure, or whether they were cancelled by default when the man in charge, Neumeister, left.

Just how serious is this? The NYT says that Neumeister’s violations include “that records had been falsified”. It turns out that the falsification consisted of Neumeister “signing a fellow investigator’s name on reports” when in fact he or another colleague wrote those reports. This doesn’t sound like the most serious kind of document manipulation. Perhaps more serious is the reported failure to complete some assessments: “the research team had failed to assess at least three subjects 24 hours after they had taken the experimental drug, contrary to study protocol”; this might have posed safety risks.Neumeister_Alexander_01 1

And who is Alexander Neumeister? He is, or was, a prolific and succesful researcher. Neumeister has published 155 scientific papers over a 20 year career, many of which have been highly cited. Neumeister’s early research was focussed on depression and especially on the role of serotonin in that disorder. His interest in the cannabinoid system appears to be relatively recent; his first cannabinoid paper is from 2011.

I’ve found no evidence that Neumeister has ever been involved in a controversy of this kind before, and he appears to have never had a paper retracted. His LinkedIn profile lists his current affiliations as “Anavex Life Sciences Corporation” and “The Catholic University of Bukavu”, in the Democratic Republic of Congo. A long way from New York.

ADVERTISEMENT
  • Neurocritic

    I was curious about this case as well. The Clinical Trial in your link was sponsored by Pfizer. Other trials (sponsored by NYU) terminated because “PI no longer at NYU” include:

    https://clinicaltrials.gov/ct2/show/NCT02237677
    https://clinicaltrials.gov/ct2/show/NCT02234687
    https://clinicaltrials.gov/ct2/show/NCT02237703

    Here’s more from the FDA warning letter:

    “1. You failed to maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation [21 CFR 312.62(b)].
    . . .

    2. You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].”

    http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm493086.htm

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Great finds, thanks!

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      It appears that concern #1, “You failed to maintain adequate and accurate case histories…”, relates entirely to the falsification of names on the records. In other words, the records themselves were valid but they were invalidated by having a false signiature.

      This doesn’t seem very serious in itself but it might be the symptom of a deeper problem.

      #2 “You failed to ensure that the investigation was conducted according to the investigational plan…” is a mixed bag of problems. It appears that the protocol was not followed and some steps were skipped e.g. according to the protocol the SCID interview was meant to be used to diagnose PTSD as an inclusion criteria, but the PTSD module was not performed in most included patients. Neumeister’s response was that he knew these patients from previous studies and that they had tested positive on the SCID for PTSD previously.

    • Nick Danger

      I don’t know if you checked, but all three of those links reference Charles Marmar. In other words, all are terminated due to one investigator.

  • Pingback: Morning Break: Watson at the VA; Pelvic Infection Rampage; Butter Not So Bad?()

  • boonteetan

    What a revelation of the dark side of medical research, or for that matter, all researches. Was it a collusion between academics and pharmaceuticals? Quite unthinkable.

  • Pingback: Weekend reads: Publisher under fire; Canadian scientists demand change; a troubled psychiatry trial - Retraction Watch at Retraction Watch()

  • Jeffrey Nevrotski

    He should be charged in a cout of law for attemted murder, falsification of federal documents, reckless endangerment. Also should have his medical license revoked permenently. Phizer needs to be held accountable also. If i had my way these companies would not be permitted to bury cures for diseases (LIKE AIDS!!! ) for a pill that treats the symptoms. Human Greed dictates its more profitable to treat not cure. These drug companies 😤😤

  • Catherine Nichols Pogorzelski

    Penance in the Jungle” movie on Lifetime coming next Spring…when will they ever learn you can’t get away with this crap!

  • disqus_xk55NgnmR2

    Hmm, the Pfizer trial is a good guess. If not, the trial in question was one that followed.

    FWIW- The woman featured in the NY times article, the one in the photo, previously ran a blog. On that blog, there was a post where she mentioned being a participant in Neumeister’s study and named the compound mentioned above. In fact, this blog was probably how the NY times located her. The site now leads to a 404 error, but can be found via Google Cache:

    http://webcache.googleusercontent.com/search?q=cache:http://www.alittlefearless.com/author/lilred/page/5/

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Good find!

  • Pingback: A prominent psychiatry researcher is dismissed. What's happening to his papers? - Retraction Watch at Retraction Watch()

  • Nick Danger

    I am involved with clinical trials. I read the FDA Inspection report. The “violations” are not huge. They are more protocol violations. I am quite uncomfortable with his false signings. I have never been involved in a trial with such cases. Who was the clinical manager for this study? That person is also culpable, and the qualifications that this person possesses should be checked. A false signing could be done simply out of convenience, or to cover up a more important issue.

  • lizwoeckner

    I may be doing something wrong but I can’t find a NY state medical license for Dr Neumeister: http://www.nydoctorprofile.com/

    From the FDA warning letter
    ” On worksheets for medical history, physical
    examinations, and neurological examinations, you personally hand-printed
    the name of your subinvestigator to indicate that these study
    procedures were conducted by your subinvestigator. However, in fact, you
    or another study employee actually conducted these study procedures,
    not your subinvestigator.”

    Taking a history and performing a physical exam constitute the practice of medicine. If the subinvestigator was a licensed physician but Neumeister was not, making it appear as if the subinvestigator performed these activities rather than Neumeister may (repeat may) suggest motive for an otherwise inexplicable, yet prohibited act.

    Does the following from the warning letter support this possibility?
    “In the August 19, 2015, written response to the Form FDA 483, Mr.
    Lederman agreed that you had performed these procedures and had your
    subinvestigator’s name added instead of your own. Mr. Lederman noted
    that the protocol did not specify to whom the responsibility of
    obtaining medical history and performing physical and neurological
    examinations could be delegated, nor did it specify that a licensed
    psychiatrist must document the psychiatric evaluations. In addition, Mr.
    Lederman stated that after your study staff collected the information
    to complete these study records, you and your subinvestigator carefully
    reviewed and discussed the eligibility of the subjects.”

    FDA regulations permit non-physicians to serve as clinical investigators (PIs) but there must be a licensed physician subinvestigator. It goes without saying the study delegation plan has to thoughtful and in compliance with applicable law, and everyone has to follow it.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Good point, I think you may well have found the answer to the mystery of why the names were manipulated.

  • MKBizate

    Does anyone know the background of the story?

    Do you know where to find the real protocol that the PI used??

NEW ON DISCOVER
OPEN
CITIZEN SCIENCE
ADVERTISEMENT

Neuroskeptic

No brain. No gain.

About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

ADVERTISEMENT

See More

@Neuro_Skeptic on Twitter

ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

Collapse bottom bar
+