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Clinical Trials, Ethics, Research, Stanford News

Should patients pay their way into clinical trials?

Should patients pay their way into clinical trials?

Photo of U.S. currency and a pharmaceutical capsuleIn a time of shrinking federal research budgets, here’s one idea for a solution: charge patients to participate in clinical trials.

Patients’ payment could fund studies that would not otherwise be conducted, said a group of medical ethicists led by Ezekiel J. Emanuel, MD, PhD, the former White House health-policy adviser who now chairs the Department of Medical Ethics and Health Policy at the University of Pennsylvania. Emanuel was asked by a group of academic investigators to review the legality and ethics of charging for enrollment in an early-phase clinical trial; he and his co-authors examine the pros and cons.

No laws or regulations prohibit pay-to-play, said the authors, and it has some upsides. By putting their money where their mouth is, patients could be demonstrating deep engagement with the research protocol, and affirming their informed consent. Their payment could be seen as a direct, Kickstarter-style version of a charitable contribution to medical research, or as an analogue to permissible payment for experimental treatments outside the confines of a clinical trial. Last but not least, there is a liberty argument, that “people should have the freedom to do whatever they want with their own money as long as they are not harming others or diminishing their rights and opportunities,” said the authors, whose perspective essay (subscription required) appears today in Science Translational Medicine.

But before going full libertarian, the authors put on the brakes. Let’s be honest, they said, this is less about a collaborative partnership than a potentially desperate need to save one’s own life; less about a charitable impulse than purchasing a service. It will skew research toward the health needs of the wealthy and could interfere with research integrity: A paying participant may be less willing to accept randomization to a control group or more reluctant to disclose symptoms and side effects. For their part, investigators might feel pressure to bend inclusion or removal criteria, or not to terminate a study. Ultimately, the authors conclude that pay-to-play is generally unethical, and warrants legislative and regulatory attention.

Co-author Govind Persad, JD, a Stanford graduate student in philosophy, told me he’s particularly concerned about participants feeling pressure to pay: “There is this real psychological pressure, if you or your kid are sick or in this desperate position, to do something that not only you wouldn’t have done, but that you see as having this direct, imminent benefit to yourself out of proportion to the benefit it’s likely to have.”

Persad hopes the essay will ignite an “educated debate” among researchers, policy makers, potential donors to medical research and people who stand to benefit from interventions to be studied in clinical trials. “An issue for people to think about going forward is: If we need more research into Condition X but pay-to-play is not the way, what would be some other good ways to try to expand the universe of trials?”

Related: A look at crowdfunding clinical trials, Can crowdfunding boost public support and financing for scientific research, Stanford forum on the future of health care in America posted online and When it comes to health-care spending, U.S. is “on a different planet”
Photo by David Goehring

Cancer, Clinical Trials, Dermatology, Genetics, Pain, Pediatrics, Research, Stanford News

The worst disease you’ve never heard of: Stanford researchers and patients battle EB

The worst disease you've never heard of: Stanford researchers and patients battle EB

EB patient and docsI’m often humbled by my job. Well, not the job, exactly, but the physicians, researchers, and especially patients who take the time to speak with me about their goals and passions, their triumphs and fears. Their insight helps me as I struggle to interpret what goes on here at the Stanford University School of Medicine for others across the university and even around the world.

But every once in a while, an article comes along that brings me to my (emotional) knees. My article “The Butterfly Effect” in the latest issue of Stanford Medicine magazine describes the toll of a devastating skin disease called epidermoloysis bullosa on two young men and their families, as well as the determined efforts of a dedicated team of doctors and scientists to find a treatment. As a result, Stanford recently launched the world’s first stem-cell based trial aimed at correcting the faulty gene in the skin cells of patients with a severe form of the condition, which is often called EB.

I trace the path of one family as they learn, mere hours after his birth, that their son, Garrett Spaulding, has EB, which compromises the ability of the outer layers of the to stick together during friction or pressure. Patients develop large blisters and open wounds over much of their bodies. It’s incurable, fatal, and nearly indescribably painful. Paul Khavari, MD, PhD, now the chair of Stanford’s Department of Dermatology, was a young doctor at the time newborn Garrett was admitted to Lucile Packard Children’s Hospital Stanford in 1997.

“His whole body, his skin was blistered and falling off everywhere someone had touched him,” Khavari recalls in the article. “His parents were devastated, of course, at a time that was supposed to be one of the most joyful of their lives.”

Garrett’s now 18 years old, but the disease is taking its toll.

You’ll also meet Paul Martinez, one of the first participants in Stanford’s new clinical trial. He’s 32, which makes him an old man in the EB community. Unlike many EB patients, he has finished high school and completed a college degree in business marketing with a dogged determination that makes me ashamed of my petty complaints about my minor life trials. And he’s done it without relying on the pain medications essential for most EB patients. As he explains in the article:

We don’t know what it is like to not be in pain. It’s just normal for us. […] I have a very high tolerance, and don’t take any pain medication. I cherish my mind a lot. Rather than feel like a zombie, I prefer to feel the pain and feel alive.

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Biomed Bites, Clinical Trials, Health Policy, Videos

The mathematics of clinical trials: A career

The mathematics of clinical trials: A career

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

Math was Philip Lavori‘s first intellectual love. After earning his PhD in mathematics at Cornell University, Lavori spent his time solving tricky calculations. But the disconnect between the world of pure mathematics, and the messy outside world where people were living and dying started to bug him.

“It soon became obvious to me that I would have enormous interest in doing research that would have direct benefits to human beings,” Lavori says in the video above.

He began offering his skills as a consultant to physicians, where he discovered a new intellectual love.

“I’ve found the problems that arose in the design of clinical trials were problems that I could attack with my mathematical skills…. That quickly led to an entire career.”

Now Lavori is chair of the Department of Health Research and Policy, and he co-directs the Stanford Center for Clinical and Translational Research and Education (Spectrum).

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Survey confirms that small number of U.S. adults, children participate in research studies, A faster, better, cheaper clinical trial (electronic record system not included) and Re-analyses of clinical trial results rare, but necessary, say Stanford researchers

Big data, Clinical Trials, Ethics, Public Health, Research, Stanford News

The public wants easier ways to participate in medical research, study shows

The public wants easier ways to participate in medical research, study shows

Informed consent, the time-consuming process for obtaining permission to conduct health-care research on a person, was developed long before computers, the Internet and smartphones. Last year, when government regulators proposed to add an even greater burden of paper, red tape and so-called patient protections to this process, a team of bioethicists cried foul. And they took the issue to the public via a cross-sectional survey study that was published today in the Annals of Internal Medicine.

What the survey respondents said surprised them: Keep the permissions simple, but always ask permission, even when the research only involves anonymized medical records.

“The good news was that most people said that they would accept simpler approaches to granting permission, even verbal permissions, if requiring written agreements would hinder this type of comparative-effectiveness research,” study author Mildred Cho, PhD, associate director of the Stanford Center for Biomedical Ethics, said in our press release.

Bioethicists from Stanford and the University of Washington are on the leading edge of addressing the ethical challenges of evolving research methods, where researchers will increasingly use data from wearable devices, electronic medical records, genomic databases and other sources to help improve our population’s health.

In an editorial accompanying Cho’s article, John Lantos, MD, from Children’s Mercy Hospitals and Clinics, summarized the importance of the study:

Cho and colleagues challenge us to think of a better way. Autonomy should mean participatory engagement. Respect for persons should mean empowering them to develop the rules. It is time to ask whether a system in which the fundamental principle is ‘respect for persons,’ can continue to ignore the preferences of many of the persons it claims to respect.

As a next step, the bioethicists will be developing media-rich tools to explain the risks and benefits of research that uses electronic medical records and stored biological samples. For example, the video above was developed to explain the concept of informed consent to survey respondents unfamiliar with research terminology.

Previously: Build it (an easy way to join research studies) and the volunteers will comeHarnessing mobile health technologies to transform human health and Video explains why doctors don’t always know best
Video by Booster Shot Media

Chronic Disease, Clinical Trials, Genetics, Patient Care, Pediatrics, Stanford News

Cystic fibrosis patient on her 20+ years of care

Cystic fibrosis patient on her 20+ years of care

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When Lauren Catron was first diagnosed with a severe form cystic fibrosis, an inherited disease that makes mucous and sweat glands go haywire, her doctors were unsure that she’d live to be a teenager. That was nearly 23 years ago. Now, 26-year-old Catron is a full-time college student at Mission College in Santa Clara, Calif. with enough energy to work a job in her spare time.

Catron credits her sustained health to the more than two decades of care she’s received at the Pulmonary and Cystic Fibrosis Center at Lucile Packard Children’s Hospital. Catron shares her story on the Happier, Healthier Lives Blog:

“When I was first diagnosed in 1992, the doctors told my parents that I may not make it to my teens,” said Catron, who has the genotype associated with a shorter lifespan and the most severe symptoms of cystic fibrosis, including a constant buildup of mucus in her lungs that interferes with breathing. “But a whole team of people at Stanford has dedicated themselves to keeping me healthy. They have given me absolute unconditional support, amazing treatment and care, and have become my second family.”

Carol Conrad, MD, director of the pediatric pulmonary function lab, explains that the center’s expert care stems from the many clinical trials and studies they do to advance the treatment of cystic fibrosis. “No other CF center in California is doing these kinds of clinical trials,” Conrad said.

This research, which ranges from dietary-supplement studies by Conrad to gene therapy work done by Richard Moss, MD, shows promise. Moss and his colleagues were the first to discover that gene therapy could improve pulmonary function in cystic fibrosis patients – an important finding that may lead to a treatment for the disease in the future. “As depressing as the disease can be, there’s a lot of hope. That’s what keeps us motivated,” said Conrad.

Previously: New Stanford-developed sweat test may aid in development of cystic fibrosis treatmentsFilm about twin sisters’ double lung transplants and battle against cystic fibrosis available onlineDiverse microbes discovered in healthy lungs shed new light on cystic fibrosis and Living – and thriving – with cystic fibrosis
Photo of Conrad (left) and Catron courtesy of Lucile Packard Children’s Hospital

Applied Biotechnology, Clinical Trials, FDA, Research, Stanford News

An inside look at drug development

An inside look at drug development

B0008664 Assorted pills, tablets and capsules

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

A recently published book, A Practical Guide to Drug Development in Academia, crystallizes the sessions. Even if you’re not a scientist dreaming of curing cancer with your latest discovery, you might find it interesting.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development and Accelerating the translation of biomedical research into clinical applications.
Photograph from Wellcome Images

Clinical Trials, In the News, Research, Stanford News, Technology

Lights, camera, action: Stanford cardiologist discusses MyHeart Counts on ABC’s Nightline

Lights, camera, action: Stanford cardiologist discusses MyHeart Counts on ABC's Nightline

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Apple’s new ResearchKit, and Stanford Medicine’s MyHeart Counts iPhone app, were highlighted on ABC’s Nightline on Friday. Michael McConnell, MD, professor of cardiovascular medicine and principal investigator for the MyHeart Counts study, was interviewed, telling business correspondent Rebecca Jarvis around the 4-minute mark that the app will “definitely” change the way his job works. “It gives us a whole new way to do research,” he explained. “Traditionally reaching many people to participate in research studies is quite challenging. The ability to reach people through their phone is one major advance.”

Previously: Build it (an easy way to join research studies) and the volunteers will comeMyHeart Counts app debuts with a splash and Stanford launches iPhone app to study heart health
Photo by Margarita Gallardo

Big data, Clinical Trials, Ethics, Public Health, Research, Stanford News, Technology

Build it (an easy way to join research studies) and the volunteers will come

Build it (an easy way to join research studies) and the volunteers will come

stanford-myheart-counts-iphone6-hero

Just nine days after the launch of Stanford Medicine’s MyHeart Counts iPhone app, 27,836 people have consented to participate in this research study on cardiovascular health.

“To recruit that many patients into a traditional clinical trial would take years and hundreds of thousands of dollars,” said Michael McConnell, MD, professor of cardiovascular medicine and principal investigator for the MyHeart Counts study.

MyHeart Counts was built with Apple’s new ResearchKit, a software development framework that can be used to create apps that turn an iPhone into a research and data collection tool. Leveraging a smartphone’s built-in accelerometers, gyroscopes, camera and GPS sensors, medical researchers can easily and inexpensively collect streams of data on exercise, diet and biometrics. Unlike most traditional clinical trials, which capture only a snapshot of patient data, ResearchKit studies are able to collect data from thousands of participants simultaneously, over long periods of time.

While the potential for this technology to accelerate medical research is tantalizing, the ethical issues of this shift in researcher-volunteer interactions took Stanford researchers and collaborator Sage Bionetworks nine months to work out.

“One of the big challenges in designing this study was to develop an ethical mechanism for informed consent on mobile devices,” David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, told me. “It was essential that volunteers understand the nature of the research and what it means for them.”

The concept of informed consent is an important tenet of any research institution’s commitment to respect individuals and to “do no harm.” Without face-to-face meeting between a researcher and volunteer, there could be misunderstandings about risks, benefits and time commitments.

Stanford bioethicists are on the leading edge of addressing the communications challenges of these new frontiers in medical research. Rethinking long, text-based consent forms, they are exploring alternatives, such as audio, video, animation and interactivity.

For example, a team of bioethicists from Stanford and the University of Washington recently released animated videos that explain comparative-effectiveness research within medical practices to potential volunteers. Next, they’ll be developing media-rich tools to explain the risks and benefits of research that uses electronic medical records and stored biological samples.

To solicit ideas on how to best regulate this brave new world of informed consent, the U.S. Food and Drug Administration just posted draft guidance on “Use of Electronic Informed Consent in Clinical Investigations.” Public comments will be accepted through May 7, 2015.

To sign up for the MyHeart Counts study, visit the iTunes store.

Previously: Harnessing mobile health technologies to transform human healthMyHeart Counts app debuts with a splashStanford launches iPhone app to study heart health and Video explains why doctors don’t always know best
Photo by iMore

Cancer, Chronic Disease, Clinical Trials, Science Policy

A look at crowdfunding clinical trials

A look at crowdfunding clinical trials

1024px-Assorted_United_States_coins I’ve been able to watch the crowdfunding phenomenon up close: My husband is a Kickstarter addict, and he, like millions of others, funds projects that speak to his passions and social priorities. In recent years, some non-profits have applied the crowdfunding model to clinical trials (something he hasn’t funded yet), and others may follow suit as federal-funding dollars dries up. Last week, Nature Medicine published an article that describes the first few years of those efforts and the questions they bring up.

As outlined in the piece, critics argue that the system unfairly penalizes those that may not have a large online social network to use to publicize their funding efforts, while proponents say it makes it possible for donors to connect more directly with the research and it increases transparency of research funding. As one source explains:

“One key thing is tangibility,” says Catherine Ferguson, Innovation Project Lead at Cancer Research UK, “It’s an inherent part of crowdfunding that isn’t inherent in regular funding.” Whether it’s a particular type of cancer or a particular therapy, crowdfunding allows for a “more direct relationship with both the researcher and the research,” she adds, emphasizing that this directed approach is good for maintaining relationships with donors.

Cancer Research UK, which we’ve written about before, was one of the early advocates of clinical trial crowdfunding. It recently concluded it first effort to crowdfund a clinical trial to study a vaccine for Epstein-Barr virus in cancer patients. The group fell far short of their goal, raising only six percent of the £40,000 ($61,000) goal on their Indiegogo campaign, so it returned the funds to donors. Again, from the article:

The organization chose a so-called fixed-funding model, in which they chose a goal amount but kept none of the funds that were raised if the goal wasn’t met. “It felt disingenuous to keep some of the money but not make the research happen,” said Ferguson. “We really wanted to emphasize that the money was for a specific project and if the project couldn’t be fully funded, then why keep the money?” Because the campaign wasn’t successful, the funds raised were returned to those who pledged the money, but Ferguson said that many of the donors reached out to make contributions to the organizations anyway.

Other organizations are using slightly different models, and the coming months, or maybe years, will reveal whether any are able to successfully fund clinical trials through this new avenue.

Previously: New crowdfunding sites apply Kickstarter model to health and medicineCan crowdfunding boost public support and financing for scientific research? and Crowdsourcing the identification of cancer cells
Photo by Elembis

Clinical Trials, Nutrition, Pediatrics, Research, Stanford News

Batman has his utility belt – and I have my EpiPen

Batman has his utility belt - and I have my EpiPen

Batman“Matt, do you have your EpiPen?” Those six words have echoed throughout my house each morning ever since I could understand them.

“Matt, do you have your EpiPen?” “Matt, do you have your EpiPen?” “Matt, do you have your EpiPen?” How many times have I heard that? Thousands. Growing up with a food allergy was a huge burden requiring constant vigilance. Vigilance about carrying my EpiPen and about knowing where to sit at the school lunch table, who would chaperone the field trip, whose birthday party my mom or dad would have to hang out at, whose house was safe for me to hang out at – and vigilance about which foods I eat.

Since enrolling and subsequently graduating from a Stanford food allergy study led by Kari Nadeau, MD, PhD, my anxiety surrounding my allergy has greatly decreased, but my vigilance remains steadfast. The Stanford study has given me safety from cross contamination and a life without fear.

Yet, just as Batman has his utility belt, I have my EpiPen. The EpiPen may as well be tattooed on to my skin, as it still travels with me everywhere I go. In my opinion, this should be the same for every severely allergic person. My good friend (who has multiple food allergies) doesn’t carry one when he’s with me. His rationale behind it is, “I’m with you, so I don’t need one.” I recently met someone who doesn’t carry an EpiPen although she has a diagnosed anaphylactic allergy to tree nuts and peanuts. Her rationale? “I’ve never had a reaction, and I am really careful about what I eat.”

I can’t understand when I meet people with food allergies and they don’t carry an EpiPen. Sometimes they say, ” I just get hives around my mouth.” Or “I just get a little itchy on my tongue.” Or “I have one – it’s in my car.” CAN YOU BE SERIOUS?

Unfortunately for me, before entering the allergy study, I had to use my trusted EpiPen several times. It was very tense, scary and thankfully quick. After a person gets over the paralyzing fear of the needle (which is actually hidden inside the pen), the EpiPen is actually easy to use (once you get the hang of it). It works so fast. It actually stops the allergic reaction in its tracks. It’s the only life-saving medication food that allergic people can use to help prevent life threatening reactions.

So yes, under the advice of my doctor, I still carry an EpiPen. Even though I successfully eat a lot (4,000 milligrams each) of all of my allergens daily, (which are wheat, rye, barley and oats), it’s always by my side – at camp, tennis, school or a party. I know the facts of how quickly a reaction can escalate, and I may still have a reaction. I am after all, a living science experiment.

The words, “Matt, do you have your EpiPen?” are still essential to my life.

Matthew Friend is a high-school junior from Chicago. A version of this piece originally appeared in the Huffington Post.

Previously: Participant in Stanford food-allergy study delves into lifestyle-changing research, Taking a bite out of food allergies: Stanford doctors exploring new way to help sufferersSimultaneous treatment for several food allergies passes safety hurdle, Stanford team shows, Researchers show how DNA-based test could keep peanut allergy at bay and A mom’s perspective on a food allergy trial and Searching for a cure for pediatric food allergies
Photo by JD Hancock

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