Jonathan Moens, Undark, March 8, 2023

IN JANUARY OF 2022, Janis Hughes was told she had two years to live. After two prior bouts of cancer, she was now told she had stage 4 breast cancer, which had already spread to her sternum, ribs, and right lung. The news devastated her, making her feel “a great weight” pressing on her chest, robbing her of any joy. One day, she came across a documentary about how psilocybin mushrooms, commonly known as magic mushrooms, combined with therapy could help people with terminal cancers get relief from their existential dread. Hughes, now 66, was not one for taking what she considered “hard drugs,” but she was intrigued.

“I had nothing to lose at this point, and it just resonated with me — oh, that’s what I need,” she said.

Getting access to these drugs, however, was not going to be easy. In Canada, where Hughes lives, it is generally illegal to use psychedelics outside of a research setting. But since 2020, the government has allowed a small number of patients to seek medical exemptions. More recently, in January 2022, Canada reversed a regulatory restriction that had prohibited patients from accessing restricted drugs, including psychedelics, through its Special Access Program. The SAP, which is overseen by Health Canada, the nation’s public health agency, allows patients with serious or life-threatening conditions to obtain emergency access to unapproved medications when conventional therapies have failed or are otherwise unsuitable.

Canada’s recent policy change makes it among the few countries in the world to explicitly offer psychedelics on a compassionate or emergency use basis.

Hughes applied through the SAP, but soon ran into a hurdle: She had to find a doctor willing to fill out an eight-page form; administer psilocybin, the psychoactive compound in magic mushrooms; and oversee the entire process. The doctor would also have to take responsibility in case anything went wrong. She asked two oncologists at her cancer center and her family physician, but all of them declined. One oncologist had never heard of psilocybin-assisted therapy for terminal cancer patients, Hughes said, and the other told her that she preferred not to get involved because of the amount of paperwork. Her family physician was open to helping with her application, she said, but didn’t want to be responsible for overseeing her use. When Hughes finally found a willing doctor, she would have to travel more than 1,000 miles across Canada to an unfamiliar city to be treated. She decided against it.

[….]

“This SAP process is really a horrible process for getting patients access to experimental drugs like psilocybin,” said Spencer Hawkswell, CEO of TheraPsil, a nonprofit psychedelic advocacy group based in British Columbia that currently works on assisting patients in applying through the SAP. “It just doesn’t work.”

Not everyone sees the SAP so bleakly. While the program may be slow, some medical ethicists and physicians say the application form asks perfectly legitimate questions and should help ensure that the drugs are prescribed safely and effectively. Psychedelics hold a lot of promise, they argue, but the evidence surrounding their use is still preliminary, so safeguarding against misuse is critical.

These experts also say that the best way to get access to these drugs is through a clinical trial, a type of study that tests how well a treatment works in humans. Such trials guarantee a certain level of safety and help health regulators compile data to rigorously identify the benefits of the drugs. “Then all patients could ideally have access to them without going through these pathways,” said Holly Fernandez Lynch, an assistant professor of medical ethics and health policy at the University of Pennsylvania.

Clinical trials specific to these patients are rare, however, and conducting one is costly. And according to the SAP’s critics, patients are often left with few legal options.

THE FIRST STUDIES specifically looking at how psychedelics could help patients with existential distress took place in the late 1960s in the United States. While the studies mostly focused on drugs other than psilocybin, they generally seemed to suggest that psychedelics could help terminal cancer patients relieve deep-seated feelings of anxiety. But those studies came to a halt in 1970, when the country’s Controlled Substances Act banned psychedelics and classified these and other drugs as “Schedule I,” meaning they were now considered to have “no currently accepted medical use” and “a high potential for abuse” by federal law.

It was only about 30 years later that scientists picked up where they had left off. Of particular importance were two seminal studies published in 2016 by researchers at Johns Hopkins University and New York University, respectively, showing that terminally ill patients experiencing distress exhibited significant improvements in mood, anxiety, quality of life, and depressive symptoms after a single high dose of psilocybin. The studies had notable limitations: The sample sizes were relatively small, about 90 percent of participants were White, and about half had post-graduate education. But, for most of the NYU study participants, the drugs had quick and positive effects that lasted at least four and a half years.

End-of-life anxiety is not an official clinical diagnosis, however, so there was no pathway to approval by the U.S. Food and Drug Administration. Scientists soon pivoted to other conditions, including treatment-resistant depression. One of the latest studies on these patients found that psilocybin alleviated depressive symptoms as well as escitalopram, an often-used antidepressant. Last November, the biggest study on this group of patients to date, with more than 200 participants, showed that a high dose of psilocybin significantly reduced depression scores.

[….] And questions about how the drug actually works in the brain still remain. Scientists are just starting to map the specific receptors, pathways, and brain regions that seem to be altered when patients are on psychedelic drugs; there is currently no consensus on what biological mechanisms might explain the drugs’ anxiety-relieving or mood-boosting effects.

“The really quick answer,” said Albert Garcia-Romeu, an assistant professor and researcher in the psychedelics research center at Johns Hopkins: “We don’t know.”

[….]

SEVERAL HEALTH EXPERTS who do not have direct ties to Health Canada or to psychedelic advocacy groups reviewed the SAP application form for Undark and said they do see merit in the questions. Among other things, the form asks for patient and drug manufacturer information, the rationale for prescribing the drug, and treatments the patients have tried already.

“None of those things strike me as an outrageous ask,” said Fernandez Lynch, the University of Pennsylvania professor.

Quite the contrary, these questions are a necessary vetting tool to ensure the safe distribution of unapproved drugs, said James Downar, the head of palliative care at the University of Ottawa.

Hawkswell acknowledged that many of the questions posed are legitimate but said that much of the wasted time comes from physicians having to answer “absurd” follow-up questions by Health Canada, like asking doctors why symptoms like suicidal ideation, severe depression, and hopelessness are unacceptable.

In one example, Health Canada asked a medical professional to provide reasons why two of his patients, who were applying to use psilocybin through the SAP, couldn’t seek other legal treatments, including electroconvulsive therapy.

While ECT is approved for treatment of severe depression, mania, and schizophrenia in Canada, the therapy is controversial and, in some cases, can lead to serious adverse effects, including memory loss. Eventually, after some discussions with the health agency and pressure from the media, the SAP approved psilocybin for all four of his patients.

The controversy highlights what critics see as the heart of the issue: Unlike physicians, SAP health officials are trained to “check boxes” that follow internal guidelines and not to carefully evaluate what treatment is best for patients, Masuda said. Requests passing through the U.S. equivalent of the SAP, known as expanded access, are also vetted by health officials within the FDA, but the final say rests squarely with the medical professional, said Diana Zuckerman, president of the National Center for Health Research, who was involved in finding ways to improve the U.S. program. In fact, she said, the FDA approves expanded access requests in virtually all instances and the relevant forms are designed to be easy to complete and take about 20 minutes.

The SAP could follow a similar model. It might also benefit from creating a standardized form with pre-written answers that physicians could check off and determine whether their patients are eligible for psychedelic drugs, said Garcia-Romeu, the Johns Hopkins researcher. That way, the process would be streamlined, there would be fewer ambiguities, and drugs would likely be more fairly distributed.

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Ed Silverman, Stat News, January 24, 2023

Amid ongoing controversy over clinical trial transparency, a new analysis found that results of 43 studies involving thousands of children were never reported to a U.S. government database or published in the scientific literature.

In some cases, medicines being studied were for such life-threatening conditions as congenital heart disease and Duchenne muscular dystrophy. One study explored the use of a particular painkiller for reducing the amount of opioids needed to treat pain following heart surgery. Another tested a drug for lowering aggression among children diagnosed with attention deficit hyperactivity disorder, or ADHD.

In each instance, the researchers scoured ClinicalTrials.gov, the federal database, and medical journals, but were unable to find results. More than 3,600 children participated across the 43 studies. There was partial information posted to the database or published in journals for another 22 studies, although the researchers noted that medical journal findings can be unreliable or omit relevant outcome data.

“When any adult or child participates in a clinical trial, they are taking a risk for the greater good, but if the results are not made public, those studies are of no help to anyone,” said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank that was one of three organizations that conducted the analysis. “Our next step is to work with Congress to fix this situation.”

The study has not yet been published in a scientific journal, but was made available on medRxiv, a preprint server. These platforms have become an increasingly popular destination for many studies before they have been peer-reviewed by medical journals.

In one instance, Astria Therapeutics failed to post results for an open label extension study of a drug to combat Duchenne muscular dystrophy. The study enrolled 130 boys. But after the Phase 3 trial failed, research into the drug was abandoned and the study was terminated. The company made the Phase 3 results available 110 days later than required by law.

But results for the extension study have still not been posted to ClinicalTrials.gov and are more than a year overdue. TranspariMED, another of the organizations that conducted the analysis, wrote that it was unable to locate final results from the extension study in scientific The company did not provide an explanation. We asked the company for an explanation and will update you accordingly.

In another instance, Phoenix Children’s Hospital ran a trial to determine whether a painkiller, ketorolac, could reduce opiates needed to treat pain in children after heart surgery. The hospital sought to enroll 166 infants and children aged between 3 months and 4 years. The primary completion date was December 2020, but results were never posted and the hospital did not respond to TranspariMED. We asked the hospital for comment and will pass along any reply.

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Erin Durkin, National Journal, February 15, 2023

Congress in December enacted new requirements that require drug- and device-makers to ensure there is sufficient diversity in their clinical trials. Yet lawmakers and advocates don’t want to stop there.

Among them is Democratic Rep. Robin Kelly, who plans to reintroduce a bill this month that would require sponsors of research funded by the National Institutes of Health to lay out recruitment goals that reflect the race, ethnicity, age, and sex of patients who have the condition being studied or that reflect the general population of the United States. Republican Rep. Brian Fitzpatrick cosponsored the measure. Republican Sen. Susan Collins and Democratic Sen. Bob Menendez sponsored a companion bill in the Senate.

“Racial and ethnic minorities are not properly represented in clinical research. That’s the bottom line,” Kelly told National Journal.

The proposal aligns with a measure enacted as part of the massive government-funding bill passed at the end of December. That provision requires drug and device sponsors to submit diversity action plans to the Food and Drug Administration. The agency is also required to develop new guidelines or update already existing guidance for these plans.

Kelly said her focus on NIH clinical trials can complement the FDA measures because there are “things that NIH will capture that FDA won’t capture.”

[….]

Eyes are now on the implementation of the new requirements for the FDA. Diana Zuckerman, president of the National Center for Health Research, said she is concerned that the new provisions lack teeth but that it is “potentially helpful” that Congress “reminds the agencies that they’re not happy with the lack of diversity.”

Ricki Fairley, cofounder and CEO of Touch, The Black Breast Cancer Alliance, said Kelly’s bill focusing on the NIH is a start, and that “we need more of this.” She said participation in a clinical trial should reflect “the burden of disease.”

“Who is getting this disease, who’s dying from it … that’s who should be in the trials. … Until we get that level of care and support, it’s not going to change,” said Fairley, who works on the campaign When We Tri(al), which aims to get more Black women to enroll in clinical trials for breast-cancer treatments.

“I know I can’t change the mind-set of a health care professional with illicit bias—I can’t change that,” she said. “What I can change—I can talk to Black women, educate Black women, and … teach them how to advocate for themselves.”

Kelly said her bill won’t fully solve the issue of diversity in clinical trials but that “it will take care of some things.” Along with submitting recruitment plans for clinical trials, the measure would require NIH and FDA to conduct a national awareness and educational campaign around the need for diverse clinical trials. She pointed to the use of “trusted messengers” during the COVID-19 pandemic to get people vaccinated.

To read the entire article, click here.