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Ethics, FDA, Health Policy, In the News, Stanford News

Stanford experts weigh in on spate of “right to try” laws for the terminally ill

Stanford experts weigh in on spate of "right to try" laws for the terminally ill

4286759185_f958aedc10_zTerminally ill patients should be able to access medication that could help them, regardless of how far along that drug might be in the FDA‘s in-depth approval process, right? Yes, some states such as Colorado, Missouri and Lousiana have said. They’ve adopted so-called “right-to-try” laws that gives dying patients access to drugs that have passed only the first stage of the FDA approval process.

Yet these laws — which are modeled on a policy from the libertarian Goldwater Institute — are ultimately useless given that federal law trumps state law, according to Stanford scholars Patricia Zettler, JD, and Henry Greely, JD, in an opinion piece published recently in JAMA Internal Medicine. In addition, the laws are redundant, they write:

Since the late 1980s, patients with serious and terminal conditions have been treated with unapproved medical products. Following sharp criticism from AIDS access about blocking access to potentially effective, but unproved, treatments, as well as congressional intent, the FDA issued regulations that are intended to provide patients with faster access to novel drugs for life-threatening conditions… Although satisfying the agency’s requirements may, at first glance, seem onerous, in practice the FDA very rarely rejects requests for expanded access.

Zettler, who formerly worked for the FDA, pointed out a link that is telling: During fiscal year 2012-2013, the FDA received 977 requests for “expanded access” (these requests may include more than one patient, Zettler said). It approved 974 of them.

None of the state or federal laws require a drug company to provide experimental drugs, and Zettler said she knows of only one - NeuralStem, Inc., a Maryland-based company that is developing therapies for central nervous system disorders –  that intends to provide drugs under these laws. By skipping the FDA’s process, the companies risk angering the FDA, whose favor they need for their drug approval, Zettler told me.

Why then these laws, which are currently also being considered in Michigan, Nevada and Arizona?

Well, Zettler told me, they’re political no-brainers. Imagine the political rants: “So-and-so made my mom die faster,” or “Joe Baloozabum opposes dying patients” – nope, that doesn’t fly inside any Beltway. Many state politicians are also motivated by a “good faith desire to help people,” Zettler said.

But she doubts that states have the expert staff needed to evaluate drug applications. And they don’t have the legal green-light either, she said, pointing out a recent ruling blocking Massachusetts’ attempt to ban a long-acting opiod.

Zettler said the state-based debates simply add a new wrinkle to a discussion that’s been percolating for decades.

Previously: No one wants to talk about dying, but we all need to and Asking the hardest questions: Talking with doctors while terminally ill
Photo by Melanie Tata

Clinical Trials, Ethics, Genetics, NIH, Pediatrics

The promise and peril of genome sequencing newborns

NICUEven though doctors and researchers have made great strides in caring for patients in the past few decades, there are still many illnesses that are difficult to diagnose, let alone treat. Among the most heartbreaking cases are those newborns who come down with mysterious illnesses that defy medical expertise. But in recent years, doctors have turned to genetic sequencing in some of these cases to identify the culprit causes of the illnesses.

Last year, the National Institutes of Health funded four pilot projects looking into the efficacy and ethics of genetic screening for otherwise inexplicable illnesses in newborns. The first of the trials will begin next week at Children’s Mercy Hospital in Kansas City, Missouri, as reported in a recent story from Nature. The trial at Children’s Mercy Hospital will focus on rapid genome sequencing with a 24-hour turn-around. Genetic sequencing normally takes weeks, but some of these infants don’t survive that long. Doctors have used similar rapid genome sequencing to diagnose an infant with cardiac defects at Lucile Packard Children’s Hospital Stanford.

Earlier this year, I had the opportunity to report on a rare genetic mutation that leads young infants to develop inflammatory bowel disease. I spoke with some parents of children with the mutation, which was identified by sequencing the children’s exome – just the protein-producing part of the genome – as part of a new project (separate from the NIH trials) at the University of Toronto in Canada. As I explain in the piece, getting a bone marrow transplant early enough can help alleviate symptoms and save the child’s life.

The parents were uniformly grateful for the sequencing technology that made it possible to understand what was causing their baby’s illness, even in cases where the child didn’t survive long after diagnosis. One mother mentioned that realizing some of the best doctors in the country didn’t know what was ailing her daughter made the experience even more frightening. After months of worried confusion about their young children’s deteriorating health, for these parents to have an answer was a relief.

But because the technique is so new, several ethical details still need clarification – which the NIH study hopes to answer. From the Nature news story:

Misha Angrist, a genomic-policy expert at Duke University in Durham, North Carolina, says that although the 24-hour genome process is impressive, it is not clear whether genomic sequencing of newborns will soon become standard practice. Many questions remain about who will pay for sequencing, who should have access to the data and how far clinicians should go in extracting genome information that is unrelated to the disease at hand. Then there is the question of how informative the process is. “I think it’s really important that we do these experiments so that we start to see what that yield is,” Angrist says.

All four teams will include an ethicist who will be responsible for dealing with questions like the ones Angrist raises. The other three trials at Boston Children’s Hospital, the University of North Carolina in Chapel Hill, and at the University of California, San Francisco are still awaiting approval from the Federal Drug Adminstration.

Previously: Stanford patient on having her genome sequenced: “This is the right thing to do for our family” When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn Assessing the challenges and opportunities when bringing whole-genome sequencing to the bedside Whole genome sequencing: The known knowns and the unknown unknowns
Photo by kqedquest

Clinical Trials, Ethics, Health Policy, Stanford News, Videos

Video explains why doctors don’t always know best

Video explains why doctors don’t always know best

“Over 85 percent of our major medical guideline recommendations are not based on high-quality evidence,” said Robert Califf, MD, director of the Duke Translational Medicine Institute, in an article I recently wrote for Inside Stanford Medicine.

This was the inconvenient truth that Stanford bioethicist David Magnus, PhD, had to explain to patients during focus groups, as he began developing policy recommendations for conducting ethical comparative-effectiveness research within physician practices.

“We had to dispel the myth that doctors always know which treatments are most effective for individual patients,” Magnus told me. “The truth is, in the absence of good evidence, these choices are often influenced by advertising, insurance coverage and local preferences.”

Gathering better treatment evidence is a key objective of the Affordable Care Act’s health-care reform mandate. It provides incentives for medical practices to continually evaluate the relative effectiveness of competing medical interventions as a way of delivering better, less costly care to more people. The widespread adoption of electronic medical records is enabling researchers to conduct these head-to-head comparisons in more automated ways, reducing the time and expense associated with the highly controlled clinical trials used to evaluate new drugs and devices.

A communications challenge with these new approaches, however, is how to explain the risks and rewards of participation to patients. In focus groups, Magnus found that no meaningful discussions could take place until his research team had educated patients on some fundamental concepts of medical research, such as standards-of-care, randomization and informed consent. To help with this process, his team produced three short, animated videos that would rapidly get everyone up to the same level of understanding. Magnus and his collaborators are making these videos available to all for educational purposes.

The first video, “Which Medication is Best?,” explores the influences and uncertainty associated with physicians’ prescribing preferences. “Research on Medical Practices” explains medical record reviews, study randomization and randomization of clinics and hospitals; and “Informing or Asking” describes ways to explain study participation to patients.

Magnus and his bioethicist collaborators from the Seattle Children’s Research Institute and University of Washington expect to publish their final ethics policy recommendations later this year.

Previously: Bioethicists say criticisms of preemie oxygen study could have “chilling effect” on clinical researchStanford biomedical ethicist discusses Choosing Wisely Initiative and Will new guidelines lead to massive statin use?
Videos by Booster Shot Media

Ethics, Genetics, Medicine and Society

Film documents rise and fall of a genome matching service – and poses tough ethical questions

Film documents rise and fall of a genome matching service - and poses tough ethical questions

Jesse_01When I think of “science fiction,” I picture three-eyed aliens with purple-and-gold tentacles — not the disturbing demise of a man, and a company, depicted in the film “The Perfect 46.”

Nor do I expect to ponder the ethics of a company that strives to produce genetically “pure” children.

Yet this is precisely the type of science fiction filmmaker Brett Ryan Bonowicz dished up to a sold-out Stanford crowd last week. Following the film, an all-star panel of genetics experts fielded questions.

The film’s premise is simple, and alluring. People can send their sequenced genome, along with their partner’s,  in to a company called The Perfect 46 and allow its proprietary algorithm to figure out if their children will be born genetic-defect free — or not.

“Jesse [Darden, the company’s CEO] wasn’t going to cure the diseases, he would just breed them out. It made a lot of people uncomfortable,” said one of the characters in the film.

So uncomfortable, in fact, that the company, and its leader Jesse Darden, played with a standout performance by actor Whit Hertford, unravels quite thoroughly – with Darden’s painful personal and professional demise forming the meat of “The Perfect 46’s” somewhat-tortured plot.

For me, the ethical quandary is a no-brainer: perfect – what fun is that? My husband and I are both far from perfect, and if we had a perfect child, it certainly wouldn’t be anything like us.

More seriously, however, the film poses thorny questions about the future of consumer genetics, a boom-and-bust field that’s both promising and terrifying. “The Perfect 46” doesn’t answer these questions, but the post-screening panelists delved into some of them.

During the talk, the experts made  it clear the technology featured in the film isn’t there – yet. Right now, if scientists sequence a genome , they don’t know the meaning of the many versions, or allele , of the gene that pop up. “Often, we don’t know if it’s disease-causing or not,” said panel member Michael Snyder, PhD, Stanford professor and chair of genetics.

Although the film takes place in the “near future,” corporations that provide basic genetic screening are already available, the experts said. And corporations may not be providing adequate counseling for potential parents, panel member Sandra Lee, PhD, a senior researcher at the Stanford Center for Biomedical Ethics, pointed out.

The Stanford-heavy audience seemed to dig the movie, but I thought the film would be more effective if its lessons were a little subtler and its pace a bit quicker.

Still, the questions it asks are real, even pressing, and not science-fictiony at all.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously:Stanford patient on having her genome sequenced: “This is the right thing to do for our family”, Stanford geneticist discusses genomics and medicine in TEDMED talk, New recommendations for genetic disclosure released and A conversation about the benefits and limitations of direct-to-consumer genetic tests
Screenshot of movie courtesy of Clindar

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Ethics, Events, Health Policy, Medicine and Society, Public Health, Transplants

Stanford Health Policy forum on organ-donation crisis now available online

Stanford Health Policy forum on organ-donation crisis now available online

The latest Stanford Health Policy Forum, which focused on ways to end our country’s organ-donor shortage, is now available online. More than 100,000 Americans currently need organ transplants, and the panelists discussed a variety of solutions for solving the problem. Among the ideas brought to the table was a compensation system for donors – an option that was also the focus of an article in today’s San Francisco Chronicle.

Previously: At Stanford Health Policy Forum, panelists dig into the issue of organ donationHow can we end the donor organ shortage?, Stanford visiting professor and founder of kidney-exchange program wins Nobel economics prize and One gift saves three young lives 

Ethics, Events, Health Policy, Stanford News, Transplants

At Stanford Health Policy Forum, panelists dig into the issue of organ donation

At Stanford Health Policy Forum, panelists dig into the issue of organ donation

Sally Satel, MD, was a practicing psychiatrist with a long history of scholarly research and policy-making in health care when a diagnosis of kidney failure popped her across the line that separates doctors from patients. Without a transplant or dialysis, the 16 percent of function left in her kidneys wouldn’t last long, and she became one of the 60,000 people in the U.S. waiting for a deceased donor kidney. That was in 2004.

One decade later, there are more than 100,000 people on that list. Last year, according to the National Kidney Foundation, just over 14,000 people received donated kidneys, a number that has remained flat since 2007. About 18 people die every day waiting on the list; another 12 are taken off the list daily because they have become too sick to survive transplant surgery. Satel was lucky – an acquaintance volunteered after others had bowed out – and Satel did receive a life-saving kidney transplant.

We need a transparent, safe and ethical system of exchange

From that unexpected experience, Satel wrote a book, ‘When Altruism Isn’t Enough: The Case for Compensating Kidney Donors,” to highlight the shortage. She also became a vocal advocate for changes in the organ donation system that could improve those increasingly dire numbers. This week, she joined a couple of thousand health professionals and interested others at the 2014 World Transplant Congress in San Francisco and also came here to participate in a Stanford Health Policy Forum on organ donation. She spoke alongside David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, and Tom Mone, former president of the Association of Organ Procurement Organizations.

The forum was hosted by the office of Lloyd Minor, MD, dean of the medical school. “Our Health Policy Forums were created to serve as a platform for experts from Stanford and across the globe to discuss important and sometimes controversial medical topics,” he said in a post-event interview. “Our hope is that fostering dialogue on issues of critical importance to our clinicians and patients will take us one step closer to developing solutions.”

At the forum, moderator/Stanford professor Keith Humphreys, PhD, began the conversation by asking Satel what it was like being on the waiting list. “It was extremely difficult,” she answered. “You’re really put in a position of facing years of dialysis (and the wait for a deceased donor kidney) can be five years. In Los Angeles, it’s almost 10 years. The average person doesn’t survive that long.” Asking friends and family isn’t easy either, she said: “You are asking someone to give you a body part.”

Satel has proposed a system of rewards – “not, a check, but some sort of in-kind incentive like a contribution to a charity or a 401k,” she said. “We need a transparent, safe and ethical system of exchange.”

The ethics of such a compensation system is what worries Magnus, who told the audience:

Every time we’ve drawn a line — ‘Here’s what we think is acceptable’ — [it’s] almost always been erased and moved somewhere else… Because of the incessant drumbeat of need, there’s a tendency to move and move the line, and maybe those moves are okay and appropriate, but it makes the slippery slope very, very, very steep. We have had only two absolutes: the rule that prohibits taking organs while people are still alive and the prohibition of payment. Both of these principles are now under attack.

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Ethics, Events, Health Policy, Stanford News, Transplants

How can we end the donor organ shortage?

How can we end the donor organ shortage?

organ donorOur country’s organ shortage is an issue of critical importance – especially to the more than 100,000 Americans currently waiting for an organ transplant. In the words of Stanford’s Keith Humphreys, PhD, “Everyone agrees that 18 people dying each day on transplant waiting lists is unacceptable, but there is fierce disagreement about what to do about it.”

Next week, Humphreys will moderate a panel discussion that delves into the issue. He’ll be joined by three experts – including Stanford bioethicist David Magnus, PhD – who will discuss the effect of the organ donation on our country’s overall health and debate the ethical and practical aspects of proposals to solve the problem. Among the most controversial proposed approach and something that will be vigorously debated: paying people to donate their organs.

The event, part of Stanford’s Health Policy Forum series, will be held on July 28 at 11 AM at the Li Ka Shing Center for Learning and Knowledge, in room LK130. For those local readers: It’s free and open to the public, but space is limited. More information can be found on the forum website.

Previously: Students launch Stanford Life Savers initiative to boost organ donation, Full-length video available for Stanford’s Health Policy Forum on serious mental illness, Stanford forum on the future of health care in America posted online and Stanford Health Policy Forum focuses on America’s methamphetamine epidemic
Photo by Mika Marttila

Ethics, In the News, Research, Transplants

Physicians more likely to become organ donors, Canadian study finds

Physicians more likely to become organ donors, Canadian study finds

When receiving advice from a physician, one might wonder what the doctor would choose for him- or herself. Recently we discussed here a study on doctors’ preferences for their own end-of-life care. Now, a study published in the Journal of the American Medical Association has reported on physicians’ views and behavior surrounding their own organ donation.

As a news@JAMA piece reports on the Canadian study, physicians are nearly 50 percent more likely than non-physicians to register as an organ donor. More from the piece:

Despite waiting lists for organs in many countries, the percentage of individuals registered in national organ donation registries in most countries is below 40%. The United States fares a bit better than average, with 48% of adults registered as organ donors.

Concerns about organ donation have led to lower-than-average rates of registration in Ontario, Canada, where only about 25% of adults have registered. Currently, there are more than 1500 people on transplant waiting lists in Ontario.

Study author Alvin Ho-ting Li, BHSc, a PhD candidate at Western University in Ontario, Canada, discusses the study’s purpose and findings further in a Q&A section of the piece.

Previously: More on doctors and end-of-life directivesStudy: Doctors would choose less aggressive end-of-life care for themselvesStudents launch Stanford Life Savers initiative to boost organ donation and Family ties: One sister saves another with live liver donation

Ethics, Genetics, Medicine and Society, Parenting, Pediatrics, Stanford News

Genome testing for children: What parents should consider

Genome testing for children: What parents should consider

Genome testing: Would you do it?

Okay, next question: Would you have your child’s whole genome tested?

In the recent issue of Stanford Medicine News, Louanne Hudgins, MD, chief of medical genetics and director of perinatal genetics at Lucile Packard Children’s Hospital Stanford, weighs in on the issue: “I strongly advise parents against whole-genome testing for their children unless performed in the context of a medical evaluation following formal counseling regarding its utility, limitations and possible unrelated findings,” she said.

In the piece, Hudgins comments on privacy and ethics considerations, and explains why what we partially know (for instance, if your child is found to have a gene predisposing him or her to a disease) can sometimes provide more cause for worry or false hope than helpful or conclusive information.

The whole piece (a short one) is worth a read.

Previously: Stanford patient on having her genome sequenced: “This is the right thing to do for our family”, Personal molecular profiling detects diseases earlier, Stanford geneticist discusses genomics and medicine in TEDMED talk and Medical practice, patents, and “custom children”: A look at the future of reproductive medicine

Ethics, Research, Sexual Health, Sports, Stanford News, Women's Health

“Drastic, unnecessary and irreversible medical interventions” imposed upon some female athletes

"Drastic, unnecessary and irreversible medical interventions" imposed upon some female athletes

Four female athletes were required to undergo “partial clitorectomies” and gonadectomies (removal of gonads) as a result of the current gender-policing polices of major sports governing bodies, according to an article published this week in the British Medical Journal.

The article, co-written by Stanford bioethicist Katrina Karkazis, PhD, raises concerns that new policies that use testosterone testing to determine eligibility for elite female athletes accused of having “male-like attributes” have resulted in unnecessary interventions that are both “invasive and irreversible.” The paper was timed to coincide with an editorial that she and Barnard College’s Rebecca Jordan-Young, PhD, wrote for the New York Times, which was previously discussed here.

Karkazis told me that both the journal article and the editorial were written in response to a case study published last year in the Journal of Clinical Endocrinology and Metabolism by physicians who conducted the medical procedures on the four female athletes. The athletes, ages 18-21 and all from developing countries, had tested high for naturally occurring testosterone levels. Their identities remain confidential, but the physicians who performed the surgeries and wrote the report acknowledged that there was no medical need for the procedures, which have been used as treatments for intersex conditions. Karkazis and colleagues argue that not only is there no medical benefit to such procedures, they also make no difference to athletic ability. From the journal article:

Clitoridectomy is not medically indicated, does not relate to real or perceived athletic “advantage,” and is beyond the policies’ mandate. Moreover, this technique is long eschewed because it has poor cosmetic outcomes and damages sexual sensation and function. Clitoral surgery should have no role in interventions undertaken for athletes’ eligibility or health.

Karkazis and her colleagues go on to refute the logic of using testosterone level testing in women as grounds for exclusion from competition as having no scientific grounds, and quote sports officials as saying that female athletes with unusually high naturally occurring testosterone levels have no more competitive advantage that other elite athletes. Karkazis and Jordan-Young wrote in the Times:

Sports officials (the report does not identify their governing-body affiliation) sent the young women to a medical center in France, where they were put through examinations that included blood tests, genital inspections, magnetic resonance imaging, X-rays and psychosexual history… Since the athletes were all born as girls but also had internal testes that produce unusually high levels of testosterone for a woman, doctors proposed removing the women’s gonads and partially removing their clitorises. All four agreed to undergo both procedures; a year later, they were allowed to return to competition.

Quite simply, these young female athletes were required to have drastic, unnecessary and irreversible medical interventions if they wished to continue in their sports.

Previously: Arguing against sex testing in athletes, Is the International Olympic Committee’s policy governing sex verification fair? and Researchers challenge proposed testosterone testing in select female Olympic athletes

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