NYAPRS Note: Following the tragic death by suicide of a man engaged in a research project at state operated New York State Psychiatric Institute (NYSPI), the federal Office for Human Research Protections has suspended research at the facility and investigators are looking into possible safety violations. The study, conducted by lead researcher Bret Rutherford who resigned in June, was testing whether the drug levodopa, which is typically used to treat Parkinson’s disease, could be used as a treatment for depression for older people, according to the NY Post. A very disturbing account by a former employee described the facility as “a high-pressure environment that often put publications ahead of study participants” and told Spectrum that “I was disappointed at the rigor of the research there” and “part of the reason why I ended up leaving and being disenchanted with the field in general.”
More details as we get them!
Shake-Up At Top Psychiatric Institute Following Suicide In Clinical Trial
By Brendan Borrell Spectrum July 31, 2023
The New York State Psychiatric Institute in New York City is undergoing an audit and a change in leadership following a suicide that occurred during one of its clinical trials.
Autism researcher Jeremy Veenstra-VanderWeele has abruptly taken the helm as the interim executive director of the institute and chair of the Columbia University psychiatry department, replacing Helen Blair Simpson, Spectrum has learned.
The New York State Psychiatric Institute is part of the New York State Office of Mental Health, but it shares buildings and staff with Columbia University and the university’s hospital. The Office of Mental Health is currently conducting an audit of the institute, according to Carla Cantor, the institute’s director of communications.
The audit and turnover in leadership comes after the halting of a series of clinical trials conducted by Columbia psychiatrist Bret Rutherford, which tested whether the drug levodopa — typically used to treat Parkinson’s disease — could improve mood and mobility in adults with depression.
During a double-blind study that began in 2019, a participant in the placebo group died by suicide. That study was suspended prior to completion, according to an update posted on ClinicalTrials.gov in 2022.
Two published reports based on Rutherford’s pilot studies have since been retracted, as Spectrum has previously reported. The National Institute of Mental Health has terminated Rutherford’s trials and did not renew funding of his research grant or K24 Midcareer Award.
Former members of Rutherford’s laboratory describe it as a high-pressure environment that often put publications ahead of study participants. “Research is important, but not more so than the lives of those who participate in it,” says Kaleigh O’Boyle, who served as clinical research coordinator there from 2018 to 2020.
Although Rutherford’s faculty page is still active, he is no longer listed in the directory at Columbia University, where he was associate professor, and the voicemail at his former number says he is no longer checking it. He did not respond to voicemails and text messages sent to his personal phone or to emails sent to his Columbia email address, and Cantor would not comment on his employment status.
The circumstances around the suicide remain unclear, and the institute has previously declined to comment on Rutherford’s retractions. Veenstra-VanderWeele confirmed that he is the new director but did not respond to further questions about the situation.
Rutherford’s studies aimed to enroll participants who had a slow walk, had only mild or moderate depression, and were not at high risk of suicide.
“You need to make absolutely certain that you are doing as much as you can to exclude people who are at risk of suicide or violence to other people,” says Carl Elliott, a bioethicist at the University of Minnesota who has written extensively and critically about a suicide in a clinical trial at his institution. “With this trial, the question I would have is: Were those things taken care of?”
It was often challenging to recruit participants who met all of the criteria set by the researchers and the institutional research ethics board, according to Emily Roberts, a former research assistant in Rutherford’s lab, who managed the clinical trial in its first year.
“In a study that is difficult to enroll for, you’re going to stretch the boundaries of who is eligible for it,” she says.
Roberts notes that many of the participants she worked with “were not well off financially” and were likely motivated by the small payments they received.
Rutherford was aiming to enroll 90 participants. To beef up recruitment, participants were reimbursed for their transportation costs and paid $15 per visit for eight visits, according to the study protocol. Those who also took part in MRI or positron emission tomography scans would receive up to $400 in additional payments.
Participants who met all the enrollment criteria but were taking an ineffective antidepressant were supposed to undergo a study-supervised taper of that medication and complete a washout period, though that was not explicitly written into the publicly available study protocol.
In January 2022, the study was temporarily suspended by the U.S. National Institute of Mental Health, following the suicide. It is unknown whether that participant had been taking any antidepressant medication prior to the study.
Four of Rutherford’s published studies were subsequently retracted or corrected for issues related to how participants taking antidepressants at enrollment were handled.
One retraction notice published in February indicates tapering could be challenging and that the researchers did not always stick to the protocol. One-third of the participants taking antidepressants were unable to successfully taper off of them.
Most of the others began the study in the middle of a planned 28-day washout period. In one case, a participant had taken antidepressant medication just one day prior to the study.
The discontinuation of antidepressants has been linked to an increased risk of suicide.
The suspended clinical trial was eventually terminated with 51 participants, according to ClinicalTrials.gov. A note appended to the results states: “Data collected in the trial have been presented as required but are considered unreliable.”
Elliott, the bioethicist, says that a fundamental problem with the way clinical trials are overseen is that ethics boards will review a protocol but not confirm that investigators are adhering to it.
As an author of one of the retracted studies, Roberts is not surprised by the anomalies in the research. “I was disappointed at the rigor of the research there,” she says, adding that it was “part of the reason why I ended up leaving and being disenchanted with the field in general.”
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.
https://doi.org/10.53053/PUPF4995
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U.S. Watchdog Halts Studies at N.Y. Psychiatric Center After a Subject’s Suicide
Human research trials at the New York State Psychiatric Institute at Columbia have been paused while regulators review whether protocols were violated.
Ellen Barry New York Times August 11, 2023
Federal regulators have suspended research on human subjects at the Columbia-affiliated New York State Psychiatric Institute, one of the country’s oldest research centers, as they investigate safety protocols across the institute after the suicide of a research participant.
A spokesperson for the U.S. Department of Health and Human Services, Kate Migliaccio-Grabill, confirmed on Wednesday that the agency’s Office for Human Research Protections was investigating the psychiatric institute “and has restricted its ability to conduct H.H.S.-supported human subject research.”
About two weeks before the federal order, on June 12, the institute had “voluntarily paused all studies that included ongoing interactions with human subjects,” according to Carla Cantor, the institute’s director of communications. The decision affected 417 studies, of which 198 have continuing participation. Of those, 124 receive federal funding.
It is unusual for the U.S. regulatory office to suspend research, and this suggests that investigators are concerned that potential violations of safety protocols occurred more broadly within the institute. Almost 500 studies, with combined budgets totaling $86 million, are underway at the institute, according to its website.
The inquiry followed the death by suicide of a person enrolled in a study led by Dr. Bret R. Rutherford, an associate professor of psychiatry at Columbia University who was testing a drug for Parkinson’s disease, levodopa, as a treatment for depression and reduced mobility in older people.
Dr. Rutherford resigned his position at the institute on June 1 and is no longer a faculty member of Columbia’s psychiatry department, Ms. Cantor said. Dr. Rutherford did not respond to requests for comment left at his home and office.
Asked about the reported suicide, Ms. Cantor would not confirm that a death had occurred during a clinical trial, saying the institute could not provide any information about study participants because of health privacy laws.
The institute’s “top priority is the health and safety of individuals engaged in our award-winning research programs,” Ms. Cantor said in a statement.
She said the institute “worked to assist federal agencies in their audit and has subsequently restructured and strengthened its research compliance and monitoring programs across the institution.”
The institute, which is operated by the state Office of Mental Health, is seeking federal approval for a new research safety plan so that federally funded studies can resume, she said. It is also conducting a safety review of human research studies not funded by the federal government, which is expected to be complete next month.
After the initial audit of the Rutherford laboratory, the National Institutes of Health requested an external audit of all federally funded research, she said.
A spokeswoman for the N.I.H., Amanda Fine, said the agency was working closely with the Office of Human Research Protections, which is investigating the matter. N.I.H. cannot discuss matters under review, she said.
The subject’s suicide was reported earlier in Spectrum, a news site focusing on autism research. But the U.S. agency’s decision to order a widespread halt to other studies had not been disclosed before now.
The trial of levodopa for late-life depression, which began in 2018 and received $736,579 in funding from the National Institute of Mental Health, aimed to recruit 90 adults over the age of 60 who suffered from mild to moderate depression and a slowed gait.
The team ended up with just 51, of whom 20 dropped out or were found ineligible, according to records provided to federal oversight agencies. The 31 who remained were assigned to one of two groups, one taking levodopa and one taking a placebo.
On the website clinicaltrials.gov, under the heading “serious adverse events,” researchers reported that the individual who died by suicide had been assigned to the placebo arm of the study.
Dr. Rutherford and his co-authors published several articles based on the trial, reporting that levodopa, which increases dopamine concentrations, led to improvement in mobility, processing and depressive symptoms in the study population.
The promising results were flagged in a commentary in The New England Journal of Medicine, which said that clinicians “might consider levodopa” for patients whose cognition or mobility did not respond to standard depression treatments.
It is not clear when the suicide occurred, but records show that the study was temporarily suspended by the National Institute of Mental Health in January 2022 and terminated in May 2023. This year, three scientific journals ran retractions identifying methodological errors in studies from Dr. Rutherford’s laboratory.
One of them pointed to a specific flaw: Eight subjects had only recently stopped taking an antidepressant, rather than waiting 28 days to “wash out,” as required by the study’s protocol. The average number of days those patients had been off medication was 10; one subject had been off medication only for a day.
A member of Columbia’s faculty since 2010, Dr. Rutherford was a prolific researcher, having received 32 grants totaling more than $15.5 million from N.I.M.H. since 2010.
Subjects in the study were paid $15 in cash for weekly visits and an additional $400 for undergoing M.R.I. and PET scans.
Emily Roberts, a former research assistant in Dr. Rutherford’s laboratory and a co-author on one of his papers, told Spectrum that recruiting for the study had been challenging and that some criteria had been relaxed to increase enrollment.
Ms. Roberts, who managed the clinical trial in its first year, said the experience left her disillusioned and contributed to her decision to leave the field. “I was disappointed at the rigor of the research there,” she said. Ms. Roberts verified her comments to Spectrum, but she would not publicly comment further on the matter.
Some studies of psychiatric drugs require participants to “wash out” — to go off the medications they are taking and allow them to clear their system, so that scientists can test the effectiveness of a new one.
This practice is specific to psychiatric research, and it creates a tension about what is best for patients, said Jeffrey Kahn, the director of the Berman Institute of Bioethics at Johns Hopkins University.
“There isn’t another category of drug trial where you ask someone to go off something they are on,” he said. “It’s a violation of a standard of care. You can’t tell someone, ‘Stop taking your chemotherapy so we can compare it to a new chemotherapy.’”
It is rare for regulators to halt research across an institution.
In 2015, the University of Minnesota suspended enrollment in psychiatric drug trials after a critical report by state auditors on the 2004 suicide of a patient who faced commitment to a state institution when he was enrolled in an industry-sponsored clinical trial of Seroquel, an antipsychotic drug.
In 2001, the Office for Human Research Protections ordered Johns Hopkins University to suspend almost all its federally financed medical research involving human subjects after the death of a volunteer who had inhaled an unapproved asthma drug.
In 2000, the federal agency temporarily suspended all medical research involving human subjects at the University of Oklahoma after an investigation showed that patients had been injected with a vaccine that had been made by unqualified laboratory workers.
If you are having thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK) or go to SpeakingOfSuicide.com/resources for a list of additional resources.