FDA describes ‘objectionable conditions’ at New York State Psychiatric Institute

The U.S. Food and Drug Administration has rebuked the institutional review board (IRB) of the New York State Psychiatric Institute in New York City for failing to follow federal regulations governing human studies.

According to a 21 March warning letter posted on the FDA’s website last week, the institute’s IRB, which is led by Corinne Rogers, did not report to the agency that a participant died by suicide during a 2021 clinical trial. The IRB also failed to share information about “serious and ongoing noncompliance” by the trial’s principal investigator, the letter says.

The agency also wrote that the IRB violated federal requirements that at least one “nonscientific member” be present at meetings that review proposed research. Non-scientist members are often lawyers, ethicists or members of the clergy, who make recommendations about informed-consent documents, among other topics.

“Failure of the IRB to prepare, maintain, and follow required written procedures raises concerns about the adequacy of the IRB’s review processes for ensuring the protection of the rights and welfare of human research subjects,” the agency wrote.

The warning letter does not name the investigator, but details about protocol violations and the timing of the suicide match a study of a depression treatment conducted by former Columbia University psychiatrist Bret R. Rutherford. The FDA sent a separate warning letter to Rutherford, also on 21 March, and noted that his failure to follow his approved study protocols “significantly impacts the safety of study subjects.”

In a written response to questions from The Transmitter, a spokesperson from the FDA wrote that the agency’s “compliance efforts, in close coordination with our federal partners, continue to monitor these and investigate other potential deficiencies.”

Last June, the Office for Human Research Protections (OHRP) at the U.S. Department of Health and Human Services halted all HHS-funded clinical research being conducted at the New York State Psychiatric Institute. The institute voluntarily paused all studies involving human participants, pending a safety review.

Leading up to the pause, two studies from Rutherford’s trial were retracted, The Transmitter reported in May, and the institute underwent leadership change in its wake, The Transmitter reported in July.

In its warning letter, the FDA noted that the IRB had previously failed to provide an action plan to prevent “the recurrence of this type of violation in the future” and gave the IRB 15 business days to address the deficiencies, or else it may be subject to regulatory action.

The institute declined to respond to specific questions sent by The Transmitter about the FDA letters. “While we cannot comment on an ongoing review, we will continue to work with the FDA regarding this matter,” a spokeswoman wrote in a statement.

The institute added that it “is fully committed to protecting the health and safety of all participants.”

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n January 2019, Rutherford began enrolling participants in a new study testing whether the Parkinson’s disease drug levodopa could be used to improve mood and mobility in adults with depression.

Participants who were taking antidepressant medications were supposed to undergo a 28-day taper to wean them off those drugs and allow them to wash out of their system prior to starting the study. The discontinuation of antidepressants can lead to an increased risk of suicide, and those participants were supposed to be closely monitored.

One participant in the placebo group died by suicide.

On 9 August 2021, the institute’s ethics board convened a meeting to discuss the suicide and determined that it met the definition of an “unanticipated problem involving risks to subjects and others,” according to the FDA’s letter.

The board is required to report such events during a trial to the OHRP and, in the case of drug studies, to the FDA as well. The board, however, instructed the investigator to report the suicide to the FDA, while the board would report it to the OHRP.

According to the FDA letter, the board also noted during the meeting that the trial had enrolled a participant who failed to meet the eligibility criteria, and that the “medication taper procedure” had not followed the protocol. (The warning letter does not specify whether this was the same person who died by suicide.)

Rutherford’s clinical trial was suspended in September 2021, a month after the board’s meeting.

During subsequent meetings in February and July 2022, the board continued to discuss issues with the tapering procedure, missing documentation from the trial, and the investigator’s failure to report a serious adverse event to the board, but it did not step in to share this information with the FDA itself, the warning letter says.

Five months later, in December 2022, the FDA began conducting an inspection of Rutherford’s laboratory and identified nine participants for whom he had failed to adhere to the antidepressant tapering and washout protocol laid out in his approved study plans, according to the warning letter to Rutherford.

The letter notes that a report prepared by the New York State Psychiatric Institute’s Office of Research Compliance and Integrity and other institutional officials found that none of those nine participants were harmed by their participation in the study.

Rutherford, who is now in private practice, did not respond to a request for comment.

In his 27 January 2023 response to the agency, he acknowledged “insufficient oversight of the study protocols” but stated that the primary intent of the medication-free period was to protect “data validity” rather than “subject safety,” according to the warning letter.

The agency disputed this point, noting that “a failure to follow the tapering and washout requirements” affects both data integrity and participant safety.

Rutherford has agreed that “data from these protocols will not be used in any future publications or grant proposals.” Two of his levodopa studies have been retracted because of these issues, and two have been corrected.

The FDA has asked him to provide further details about his action plan to prevent similar violations in the future or else he may be subject to regulatory action.

The institute has experienced turnover in its leadership in the aftermath of the suicide and subsequent reviews of research safety. In July 2023, after 17 months as the interim head, Helen Blair Simpson stepped down and was replaced by Jeremy Veenstra-VanderWeele.

Last month, Joshua Gordon, director of the National institute of Mental Health, was named the next director of the institute. His appointment is slated to begin on 15 August.

If you or someone you know is having suicidal thoughts, help is available. Here is a worldwide directory of resources and hotlines that you can call for support.