Shake-up at top psychiatric institute following suicide in clinical trial

Brendan Borrell

Spectrum News

Originally posted 31 July 23

Here are two excerpts:

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Two published reports based on Rutherford’s pilot studies have since been retracted, as Spectrum has previously reported.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.

(cut)

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.

The info is here.

Note: The article serves as a cautionary tale about the risks of clinical trials. While clinical trials can be a valuable way to test new drugs and treatments, they also carry risks. Participants in clinical trials may be exposed to experimental drugs that have not been fully tested, and they may experience side effects that are not well-understood.  Ethical researchers must follow guidelines and report accurate results.

Experts Are Ringing Alarms About Elon Musk’s Brain Implants

Noah Kirsch

Daily Beast

Posted 25 Jan 2021

Here is an excerpt:

“These are very niche products—if we’re really only talking about developing them for paralyzed individuals—the market is small, the devices are expensive,” said Dr. L. Syd Johnson, an associate professor in the Center for Bioethics and Humanities at SUNY Upstate Medical University.

“If the ultimate goal is to use the acquired brain data for other devices, or use these devices for other things—say, to drive cars, to drive Teslas—then there might be a much, much bigger market,” she said. “But then all those human research subjects—people with genuine needs—are being exploited and used in risky research for someone else’s commercial gain.”

In interviews with The Daily Beast, a number of scientists and academics expressed cautious hope that Neuralink will responsibly deliver a new therapy for patients, though each also outlined significant moral quandaries that Musk and company have yet to fully address.

Say, for instance, a clinical trial participant changes their mind and wants out of the study, or develops undesirable complications. “What I’ve seen in the field is we’re really good at implanting [the devices],” said Dr. Laura Cabrera, who researches neuroethics at Penn State. “But if something goes wrong, we really don't have the technology to explant them” and remove them safely without inflicting damage to the brain.

There are also concerns about “the rigor of the scrutiny” from the board that will oversee Neuralink’s trials, said Dr. Kreitmair, noting that some institutional review boards “have a track record of being maybe a little mired in conflicts of interest.” She hoped that the high-profile nature of Neuralink’s work will ensure that they have “a lot of their T’s crossed.”

The academics detailed additional unanswered questions: What happens if Neuralink goes bankrupt after patients already have devices in their brains? Who gets to control users’ brain activity data? What happens to that data if the company is sold, particularly to a foreign entity? How long will the implantable devices last, and will Neuralink cover upgrades for the study participants whether or not the trials succeed?

Dr. Johnson, of SUNY Upstate, questioned whether the startup’s scientific capabilities justify its hype. “If Neuralink is claiming that they’ll be able to use their device therapeutically to help disabled persons, they’re overpromising because they’re a long way from being able to do that.”

Neuralink did not respond to a request for comment as of publication time.

The info is here.

FDA and NIH let clinical trial sponsors keep results secret and break the law

Charles Piller
sciencemag.org
Originally posted 13 Jan 20

For 20 years, the U.S. government has urged companies, universities, and other institutions that conduct clinical trials to record their results in a federal database, so doctors and patients can see whether new treatments are safe and effective. Few trial sponsors have consistently done so, even after a 2007 law made posting mandatory for many trials registered in the database. In 2017, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) tried again, enacting a long-awaited “final rule” to clarify the law’s expectations and penalties for failing to disclose trial results. The rule took full effect 2 years ago, on 18 January 2018, giving trial sponsors ample time to comply. But a Science investigation shows that many still ignore the requirement, while federal officials do little or nothing to enforce the law.

(cut)

Contacted for comment, none of the institutions disputed the findings of this investigation. In all 4768 trials Science checked, sponsors violated the reporting law more than 55% of the time. And in hundreds of cases where the sponsors got credit for reporting trial results, they have yet to be publicly posted because of quality lapses flagged by ClinicalTrials.gov staff.

The info is here.

NIH adopts new rules on human research, worrying behavioral scientists

William Wan
The Washington Post
Originally posted January 24, 2018

Last year, the National Institutes of Health announced plans to tighten its rules for all research involving humans — including new requirements for scientists studying human behavior — and touched off a panic.

Some of the country’s biggest scientific associations, including the American Psychological Association and Federation of Associations in Behavioral and Brain Sciences, penned impassioned letters over the summer warning that the new policies could slow scientific progress, increase red tape and present obstacles for researchers working in smaller labs with less financial and administrative resources to deal with the added requirements. More than 3,500 scientists signed an open letter to NIH director Francis Collins.

The new rules are scheduled to take effect Thursday. They will have a big impact on how research is conducted, especially in fields like psychology and neuroscience. NIH distributes more than $32 billion each year, making it the largest public funder of biomedical and health research in the world, and the rules apply to any NIH-supported work that studies human subjects and is evaluating the effects of interventions on health or behavior.

The article is here.

Japanese doctor who exposed a drug too good to be true calls for morality and reforms

Tomoko Otake
Japan Times
Originally posted November 15, 2017

Here is an excerpt:

Kuwajima says the Diovan case is a sobering reminder that large-scale clinical trials published in top medical journals should not be blindly trusted, as they can be exploited by drugmakers rushing to sell their products before their patents run out.

“I worked at a research hospital and had opportunities to try new or premarket drugs on patients, so I knew from early on that Diovan and the same class of drugs called ARB wouldn’t work, especially for elderly patients,” Kuwajima recalled in a recent interview at Tokyo Metropolitan Geriatric Hospital, where he has retired from full-time practice but still sees patients two days a week. “I had a strong sense of crisis that hordes of elderly people — whose ranks were growing as the population grayed — would be prescribed a drug that didn’t work.”

Kuwajima said he immediately found the Diovan research suspicious because the results were just too good to be true. This was before Novartis admitted that it had paid five professors conducting studies at their universities a total of ¥1.1 billion in “research grants,” and even had Shirahashi, a Novartis employee purporting to be a university lecturer, help with statistical analyses for the papers.

The article is here.

Peter Thiel sponsors offshore testing of herpes vaccine, sidestepping U.S. safety rules

Marisa Taylor
Kaiser News
Originally posted August 28, 2017

Here is an excerpt:

“What they’re doing is patently unethical,” said Jonathan Zenilman, chief of Johns Hopkins Bayview Medical Center’s Infectious Diseases Division. “There’s a reason why researchers rely on these protections. People can die.”

The risks are real. Experimental trials with live viruses could lead to infection if not handled properly or produce side effects in those already infected. Genital herpes is caused by two viruses that can trigger outbreaks of painful sores. Many patients have no symptoms, though a small number suffer greatly. The virus is primarily spread through sexual contact, but also can be released through skin.

The push behind the vaccine is as much political as medical. President Trump has vowed to speed up the FDA’s approval of some medicines. FDA Commissioner Scott Gottlieb, who had deep financial ties to the pharmaceutical industry, slammed the FDA before his confirmation for over-prioritizing consumer protection to the detriment of medical innovations.

“This is a test case,” said Bartley Madden, a retired Credit Suisse banker and policy adviser to the conservative Heartland Institute, who is another investor in the vaccine. “The FDA is standing in the way, and Americans are going to hear about this and demand action.”

American researchers are increasingly going offshore to developing countries to conduct clinical trials, citing rising domestic costs. But in order to approve the drug for the U.S. market, the FDA requires that clinical trials involving human participants be reviewed and approved by an IRB or an international equivalent. The IRB can reject research based on safety concerns.

The article is here.

A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial

Alexander Masters and Dominic Nutt
Journal of Medical Ethics 
Published Online First: 06 June 2017.

Abstract

Many potential therapeutic agents are discarded before they are tested in humans. These are not quack medications. They are drugs and other interventions that have been developed by responsible scientists in respectable companies or universities and are often backed up by publications in peer-reviewed journals. These possible treatments might ease suffering and prolong the lives of innumerable patients, yet they have been put aside. In this paper, we outline a novel mechanism—the Plutocratic Proposal—to revive such neglected research and fund early phase clinical trials. The central idea of the Proposal is that any patient who rescues a potential therapeutic agent from neglect by funding early phase clinical trials (either entirely or in large part) should be offered a place on the trial.

The article is here.

A Clinical Trial and Suicide Leave Many Questions: Part 4: The University of Minnesota’s Response

By Judy Stone | January 8, 2013
Scientific American

Demystifying drug development, clinical research, medicine, and the role ethics plays

In earlier posts, we’ve looked at issues of consent, investigator responsibilities, and conflicts of interest on the case of Dan Markingson’s suicide while participating in a clinical trial of anti-psychotics at the University of Minnesota. This time, we turn to the University’s response.

 Not surprisingly, the University has claimed it has no responsibility for any wrongdoing—that in fact, no wrongdoing even occurred. But there are some inconsistencies in the story and unanswered questions. There is also concern over how the University has responded to criticism. We’ll examine these issues in this post.

Background regarding the University’s response

In response to the Minnesota Board of Social Work’s “corrective action” vs. Jeanne Kenney, the social worker/study coordinator who did most of the study assessments on Markingson, the UMN’s General Counsel Mark Rotenberg stated, “As we’ve stated previously, the Markingson case has been exhaustively reviewed by federal, state and academic bodies since 2004. The FDA, the Hennepin County District Court, the Minnesota Board of Medical Practice, the Minnesota Attorney General’s Office and the University’s Institutional Review Board have all reviewed the case. None found fault with the University. None found fault with any of our faculty. Most importantly, none found any causal link between the CAFE trial and the death of Mr. Markingson.”

Yet a number of UMN faculty have remaining concerns and have requested an independent investigation. Two years ago, eight faculty members in the Bioethics Department wrote Rotenberg, citing the University’s conflicts of interest in the matter. The UMN declines to reexamine the case, saying that they have been exonerated. In October 2012, Dr. Carl Elliott, Professor in the UMN Center for Bioethics, wrote Dr. Debra DeBruin, director of the Clinical Research Ethics Consultation Service for the UMN Clinical and Translational Science Institute, again requesting a review. This time Dr. Elliott expressed concern regarding human subjects protections in other trials conducted by the psychiatry department as well. As always, Dr. Elliott’s concerns were thoroughly documented. Once again, the University has turned away.

The entire story is here.

Thanks to Tom Fink for this story.

Are Psychiatric Medications Making Us Sicker?

By John Horgan

The Chronicle of Higher Education

Three years ago, I was reminded in dramatic fashion of the chasm between psychiatry and more-effective branches of medicine. My 14-year-old son, Mac, while playing lacrosse, emerged from a collision with his right arm askew. I drove him to a local hospital, where an orthopedic surgeon on duty immediately diagnosed the injury: dislocated elbow. He gave Mac an oral and local anesthetic and put him in a portable X-ray machine that showed Mac's elbow joint on a screen, in real time. Watching the screen, the doctor quickly snapped Mac's elbow back into place.

Overcome with gratitude to the doctor, I was leading my groggy son out of the hospital when my cellphone rang. An old friend, whom I'll call Phil, was on the line. He was in the psychiatric ward of a New York hospital, to which his 16-year-old son had been committed. The boy, who was taking antidepressants for depression, had threatened to commit suicide, not for the first time. The doctors were recommending electroconvulsive therapy, or ECT. Knowing that I had written about shock therapy and other psychiatric treatments, Phil asked my opinion. The fact that Phil had called me, a mere journalist, for advice in such a dire situation spoke volumes about the troubles of modern psychiatry.

I first took a close look at treatments for mental illness 15 years ago while researching an article for Scientific American. At the time, sales of a new class of antidepressants, selective serotonin reuptake inhibitors, or SSRI's, were booming. The first SSRI, Prozac, had quickly become the most widely prescribed drug in the world. Many psychiatrists, notably Peter D. Kramer, author of the best seller Listening to Prozac, touted SSRI's as a revolutionary advance in the treatment of mental illness. Prozac, Kramer said in a phrase that I hope now haunts him, could make patients "better than well."

Clinical trials told a different story. SSRI's are no more effective than two older classes of antidepressants, tricyclics and monoamine oxidase inhibitors. What was even more surprising to me—given the rave reviews Prozac had received from Kramer and others—was that antidepressants as a whole were not more effective than so-called talking cures, whether cognitive behavioral therapy or even old-fashioned Freudian psychoanalysis. According to some investigators, treatments for depression and other common ailments work—if they do work—by harnessing the placebo effect, the tendency of a patient's expectation of improvement to become self-fulfilling. I titled my article "Why Freud Isn't Dead." Far from defending psychoanalysis, my point was that psychiatry has made disturbingly little progress since the heyday of Freudian theory.

The entire story can be read here.