Is Red Tape Depriving Patients of Life-Altering Therapies?
Rich Mancuso suffered from herpes for most of his adult life. The 49-year-old New Jersey resident was miserable. He had at least two to three outbreaks every month with painful and unsightly sores on his face and in his eyes, yet the drugs he took to control the disease had terrible side effects--agonizing headaches and severe stomach disturbances.
Last week, the FDA launched a criminal investigation to determine whether the biotech behind the vaccine had violated regulations.
So in 2016, he took an unusual step: he was flown to St. Kitt's, an island in the West Indies, where he participated in a clinical trial of a herpes vaccine, and received three injections of the experimental therapeutic during separate visits to the island. Within a year, his outbreaks stopped. "Nothing else worked," says Mancuso, who feels like he's gotten his life back. "And I've tried everything on the planet."
Mancuso was one of twenty genital herpes sufferers who were given the experimental vaccine in tests conducted on the Caribbean island and in hotel rooms near the campus of Southern Illinois University in Springfield where the vaccine's developer, microbiologist William Halford, was on the faculty. But these tests were conducted under the radar, without the approval or safety oversight of the Food and Drug Administration or an institutional review board (IRB), which routinely monitor human clinical trials of experimental drugs to make sure participants are protected.
Last week, the FDA launched a criminal investigation to determine whether anyone from SIU or Rational Vaccines, the biotech behind the vaccine, had violated regulations by aiding Halford's research. The SIU scientist was a microbiologist, not a medical doctor, which means that volunteers were not only injected with an unsanctioned experimental treatment but there wasn't even routine medical oversight.
On one side are scientists and government regulators with legitimate safety concerns....On the other are desperate patients and a dying scientist willing to go rogue in a foreign country.
Halford, who was stricken with a rare form of a nasal cancer, reportedly bypassed regulatory rules because the clock was ticking and he wanted to speed this potentially life-altering therapeutic to patients. "There was no way he had enough time to raise $100 million to test the drugs in the U.S.," says Mancuso, who became friends with Halford before he died in June of 2017 at age 48. "He knew if he didn't do something, his work would just die and no one would benefit. This was the only way."
But was it the only way? Once the truth about the trial came to light, public health officials in St. Kitt's disavowed the trial, saying they had not been notified that it was happening, and Southern Illinois University's medical school launched an investigation that ultimately led to the resignation of three employees, including a faculty member, a graduate student and Halford's widow. Investors in Rational Vaccines, including maverick Silicon Valley billionaire Peter Thiel, demanded that all FDA rules must be followed in future tests.
"Trials have to yield data that can be submitted to the FDA, which means certain requirements have to be met," says Jeffrey Kahn, a bioethicist at Johns Hopkins University in Baltimore. "These were renegade researchers who exposed people to unnecessary risks, which was hugely irresponsible. I don't know what they expected to do with the research. It was a waste of money and generated data that can't be used because no regulator would accept it."
But this story illuminates both sides of a thorny issue. On one side are scientists and government regulators with legitimate safety concerns who want to protect volunteers from very real risks—people have died even in closely monitored clinical trials. On the other, are desperate patients and a dying scientist willing to go rogue in a foreign country where there is far less regulatory scrutiny. "It's a balancing act," says Jennifer Miller, a medical ethicist at New York University and president of Bioethics International. "You really need to protect participants but you also want access to safe therapies."
"Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
This requirement—that tests show a drug is safe and effective before it can win regulatory approval--dates back to 1962, when the sedative thalidomide was shown to have caused thousands of birth defects in Europe. But clinical trials can be costly and often proceed at a glacial pace. Typically, companies shell out more than $2.5 billion over the course of the decade it normally takes to shepherd a new treatment through the three phases of testing before it wins FDA approval, according to a 2014 study by the Tufts Center for the Study of Drug Development. Yet only 11.8 percent of experimental therapies entering clinical tests eventually cross the finish line.
The upshot is that millions can suffer and thousands of people may die awaiting approvals for life saving drugs, according to Elizabeth Parrish, the founder and CEO of BioViva, a Seattle-based biotech that aims to provide data collection platforms to scientists doing overseas tests. "Going offshore to places where it's legal to take a therapeutic can created expedited routes for patients to get therapies for which there is a high level of need," she says. "Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
Parrish herself was frustrated with the slow pace of gene therapy trials; scientists worried about the risks associated with fixing mutant DNA. To prove a point, she traveled to a clinic in Colombia in 2015 where she was injected with two gene therapies that aim to improve muscle function and lengthen telomeres, the caps on the end of chromosomes that are linked to aging and genetic diseases. Six months later, the therapy seemed to have worked—her muscle mass had increased and her telomeres had grown by 9 percent, the equivalent of turning back 20 years of aging, according to her own account. Yet the treatments are still unavailable here in the U.S.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape around testing emerging new science, like gene therapies or stem cells. Plus, clinical trials are cheaper to conduct, it's easier to recruit volunteers, especially ones who are treatment naïve, and these human tests can reveal whether local populations actually respond to a particular therapy. "We do have an exhaustive framework for running clinical trials that are aligned with international requirements," says Ernesto Albaga, an attorney with Hogan Lovells in Mexico City who specializes in the life sciences. "But our environment is still not as stringent as it is in other places, like the U.S."
The fact is American researchers are increasingly testing experimental drugs outside of the U.S., although virtually all of them are monitored by local scientists who serve as co-investigators. In 2017 alone, more than 86 percent of experimental drugs seeking FDA approval have been tested, at least in part, in foreign countries, like Mexico, China, Russia, Poland and South Africa, according to an analysis by STAT. However, in places without strict oversight, such as Russia and Georgia, results may be fraudulent, according to one 2017 report in the New England Journal of Medicine. And in developing countries, the poor can become guinea pigs. In the early 2000s, for example, a test in Uganda of an AIDS drug resulted in thousands of unreported serious adverse reactions and 14 deaths; in India, eight volunteers died during a test of the anti-clotting drug, Streptokinase—and test subjects didn't even know they were part of a clinical trials.
Still, "the world is changing," concludes Dr. Jennifer Miller of NYU. "We need to figure out how to get safe and effective drugs to patients more quickly without sacrificing too much protection."
Time to visit your TikTok doc? The good and bad of doctors on social media
Rakhi Patel has carved a hobby out of reviewing pizza — her favorite food — on Instagram. In a nod to her preferred topping, she calls herself thepepperoniqueen. Photos and videos show her savoring slices from scores of pizzerias. In some of them, she’s wearing scrubs — her attire as an inpatient neurology physician associate at Tufts Medical Center in Boston.
“Depending on how you dress your pizza, it can be more nutritious,” said Patel, who suggests a thin crust, sugarless tomato sauce and vegetables galore as healthier alternatives. “There are no boundaries for a health care professional to enjoy pizza.”
Beyond that, “pizza fuels my mental health and makes me happy, especially when loaded with pepperoni,” she said. “If I’m going to be a pizza connoisseur, then I also need to take care of my physical health by ensuring that I get at least three days of exercise per week and eat nutritiously when I’m not eating pizza.”
She’s among an increasing number of health care professionals, including doctors and nurses, who maintain an active persona on social media, according to bioethics researchers. They share their hobbies and interests with people inside and outside the world of medicine, helping patients and the public become acquainted with the humans behind the scrubs or white coats. Other health care experts limit their posts to medical topics, while some opt for a combination of personal and professional commentaries. Depending on the posts, ethical issues may come into play.
“Health care professionals are quite prevalent on social media,” said Mercer Gary, a postdoctoral researcher at The Hastings Center, an independent bioethics research institute in Garrison, New York. “They’ve been posting on #medTwitter for many years, mainly to communicate with one another, but, of course, anyone can see the threads. Most recently, doctors and nurses have become a presence on TikTok.”
On social media, many health care providers perceive themselves to be “humanizing” their profession by coming across as more approachable — “reminding patients that providers are people and workers, as well as repositories of medical expertise,” Gary said. As a result, she noted that patients who are often intimidated by clinicians may feel comfortable enough to overcome barriers to scheduling health care appointments. The use of TikTok in particular may help doctors and nurses connect with younger followers.
When health care providers post on social media, they must bear in mind that they have legal and ethical duties to their patients, profession and society, said Elizabeth Levy, founder and director of Physicians for Justice.
While enduring three years of pandemic conditions, many health care professionals have struggled with burnout, exhaustion and moral distress. “Much health care provider content on social media seeks to expose the difficulties of the work,” Gary added. “TikTok and Instagram reels have shown health care providers crying after losing a patient or exhausted after a night shift in the emergency department.”
A study conducted in Beijing, China and published last year found that TikTok is the world’s most rapidly growing video application, amassing 1.6 billion users in 2021. “More and more patients are searching for information on genitourinary cancers via TikTok,” the study’s authors wrote in Frontiers in Oncology, referring to cancers of the urinary tracts and male reproductive organs. Among the 61 sample videos examined by the researchers, health care practitioners contributed the content in 29, or 47 percent, of them. Yet, 22 posts, 36 percent, were misinformative, mostly due to outdated information.
More than half of the videos offered good content on disease symptoms and examinations. The authors concluded that “most videos on genitourinary cancers on TikTok are of poor to medium quality and reliability. However, videos posted by media agencies enjoyed great public attention and interaction. Medical practitioners could improve the video quality by cooperating with media agencies and avoiding unexplained terminologies.”
When health care providers post on social media, they must bear in mind that they have legal and ethical duties to their patients, profession and society, said Elizabeth Levy, founder and director of Physicians for Justice in Irvine, Calif., a nonprofit network of volunteer physicians partnering with public interest lawyers to address the social determinants of health.
“Providers are also responsible for understanding the mechanics of their posts,” such as who can see these messages and how long they stay up, Levy said. As a starting point for figuring what’s acceptable, providers could look at social media guidelines put out by their professional associations. Even beyond that, though, they must exercise prudent judgment. “As social media continues to evolve, providers will also need to stay updated with the changing risks and benefits of participation.”
Patients often research their providers online, so finding them on social media can help inform about values and approaches to care, said M. Sara Rosenthal, a professor and founding director of the program for bioethics and chair of the hospital ethics committee at the University of Kentucky College of Medicine.
Health care providers’ posts on social media also could promote patient education. They can advance informed consent and help patients navigate the risks and benefits of various treatments or preventive options. However, providers could violate ethical principles if they espouse “harmful, risky or questionable therapies or medical advice that is contrary to clinical practice guidelines or accepted standards of care,” Rosenthal said.
Inappropriate self-disclosure also can affect a provider’s reputation, said Kelly Michelson, a professor of pediatrics and director of the Center for Bioethics and Medical Humanities at Northwestern University’s Feinberg School of Medicine. A clinician’s obligations to professionalism extend beyond those moments when they are directly taking care of their patients, she said. “Many experts recommend against clinicians ‘friending’ patients or the families on social media because it blurs the patient-clinician boundary.”
Meanwhile, clinicians need to adhere closely to confidentiality. In sharing a patient’s case online for educational purposes, safeguarding identity becomes paramount. Removing names and changing minor details is insufficient, Michelson said.
“The patient-clinician relationship is sacred, and it can only be effective if patients have 100 percent confidence that all that happens with their clinician is kept in the strictest of confidence,” she said, adding that health care providers also should avoid obtaining information about their patients from social media because it can lead to bias and risk jeopardizing objectivity.
Academic clinicians can use social media as a recruitment tool to expand the pool of research participants for their studies, Michelson said. Because the majority of clinical research is conducted at academic medical centers, large segments of the population are excluded. “This affects the quality of the data and knowledge we gain from research,” she said.
Don S. Dizon, a professor of medicine and surgery at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, uses LinkedIn and Doximity, as well as Twitter, Instagram, TikTok, Facebook, and most recently, YouTube and Post. He’s on Twitter nearly every day, where he interacts with the oncology community and his medical colleagues.
Also, he said, “I really like Instagram. It’s where you will see a hybrid of who I am professionally and personally. I’ve become comfortable sharing both up to a limit, but where else can I combine my appreciation of clothes with my professional life?” On that site, he’s seen sporting shirts with polka dots or stripes and an occasional bow-tie. He also posts photos of his cats.
Don S. Dizon, a professor of medicine and surgery at Brown, started using TikTok several years ago, telling medical stories in short-form videos.
Don S. Dizon
Dizon started using TikTok several years ago, telling medical stories in short-form videos. He may talk about an inspirational patient, his views on end-of-life care and death, or memories of people who have passed. But he is careful not to divulge any details that would identify anyone.
Recently, some people have become his patients after viewing his content on social media or on the Internet in general, which he clearly states isn’t a forum for medical advice. “In both situations, they are so much more relaxed when we meet, because it’s as if they have a sense of who I am as a person,” Dizon said. “I think that has helped so much in talking through a cancer diagnosis and a treatment plan, and yes, even discussions about prognosis.”
He also posts about equity and diversity. “I have found myself more likely to repost or react to issues that are inherently political, including racism, homophobia, transphobia and lack-of-access issues, because medicine is not isolated from society, and I truly believe that medicine is a social justice issue,” said Dizon, who is vice chair of diversity, equity, inclusion and professional integrity at the SWOG Cancer Research Network.
Through it all, Dizon likes “to break through the notion of doctor as infallible and all-knowing, the doctor as deity,” he said. “Humanizing what I do, especially in oncology, is something that challenges me on social media, and I appreciate the opportunities to do it on TikTok.”
Could this habit related to eating slow down rates of aging?
Last Thursday, scientists at Columbia University published a new study finding that cutting down on calories could lead to longer, healthier lives. In the phase 2 trial, 220 healthy people without obesity dropped their calories significantly and, at least according to one test, their rate of biological aging slowed by 2 to 3 percent in over a couple of years. Small though that may seem, the researchers estimate that it would translate into a decline of about 10 percent in the risk of death as people get older. That's basically the same as quitting smoking.
Previous research has shown that restricting calories results in longer lives for mice, worms and flies. This research is unique because it applies those findings to people. It was published in Nature Aging.
But what did the researchers actually show? Why did two other tests indicate that the biological age of the research participants didn't budge? Does the new paper point to anything people should be doing for more years of healthy living? Spoiler alert: Maybe, but don't try anything before talking with a medical expert about it. I had the chance to chat with someone with inside knowledge of the research -- Dr. Evan Hadley, director of the National Institute of Aging's Division of Geriatrics and Clinical Gerontology, which funded the study. Dr. Hadley describes how the research participants went about reducing their calories, as well as the risks and benefits involved. He also explains the "aging clock" used to measure the benefits.
Evan Hadley, Director of the Division of Geriatrics and Clinical Gerontology at the National Institute of Aging
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