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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

Big data, Clinical Trials, FDA, NIH, Research, Science

Transparency in clinical trials: The importance of getting the whole picture

Transparency in clinical trials: The importance of getting the whole picture

New rules for clinical trials Scope blog 2015.02.02Last week, the Journal of the American Medical Association ran a Viewpoint article from Francis Collins, MD, PhD, director of the National Institutes of Health and Kathy Hudson, PhD, deputy director of NIH, about the U.S. Health and Human Services’s plans to beef up transparency of clinical trials of FDA-regulated drugs and devices.

As they write, the rate of results-sharing for clinical trials is fairly dismal. Some of the reasons for this go beyond researchers; for example, it’s extremely difficult to get negative results published in scientific journals. Collins and Hudson point out that another avenue exists for sharing summary results: NIH’s ClinicalTrials.gov website. But even there, less than one-third of researchers had shared results within four years of the end of their studies. Collins and Hudson are critical of this lapse in data sharing:

Without access to complete information about a particular scientific question, including negative or inconclusive data, duplicative studies may be initiated that unnecessarily put patients at risk or expose them to interventions that are known to be ineffective for specific uses. If multiple related studies are conducted but only positive results are reported, publication bias can distort the evidence base. Incomplete knowledge can then be incorporated into clinical guidelines and patient care. However, one of the greatest harms from nondisclosure of results may be the erosion of the trust accorded to researchers by trial participants and, when public funds are used, by taxpayers.

The new rules make the expectations to report some summary details about clinical trials, including adverse events, explicit. Although NIH has always encouraged sharing of summary results, the rules haven’t always been explicit. Now that there will be detailed guidance, the penalty for not complying will be harsher:

Thus, with the implementation of clearer requirements, augmented support materials and resources, and facilitated reporting, the NIH expects that investigators and sponsoring organizations will have the necessary tools to provide accurate, complete, and timely trial results submissions. However, for grantees who are subject to the amendments act and fail to comply after sufficient notification, the law is clear that NIH and other federal funders of clinical trials must then withhold further funding for the grant and any future grant to the grantee. In addition, the timely reporting of clinical trials will be taken into consideration during review of subsequent applications for funding.

The proposed changes to the regulations are currently in the public comment period, which will end in a few weeks, on February 19. After a review of the comments (and possible revisions), a final rule will likely be issued in a few months time. Once the rule goes into effect, it will be interesting to watch how this changes the research process for new NIH and FDA-regulated studies.

Previously: Shake up research rewards to improve accuracy, says Stanford’s John IoannidisRe-analyses of clinical trial results rare, but necessary, say Stanford researchersHow important is it to publish negative results?Researchers call for “democratization” of clinical trials data and A critical look at the difficulty of publishing “negative” results
Photo by U.S. Department of Defense

Clinical Trials, Patient Care, Public Health, Research, Stanford News

Screening for diseases doesn’t necessarily save lives, study shows

Screening for diseases doesn't necessarily save lives, study shows

6143531948_a9bdfe6fb5_zIt seems like it should work: If everyone was tested for every disease, lives would be saved, right? These conditions would be spotted quickly, treated and voilà – the deadly disorder would go away.

Not necessarily, according to a new study from a team led by Stanford epidemiologist John Ioannidis, MD, DSc, published this week in the International Journal of  Epidemiology. Here’s Ioannidis:

Screening for diseases that can lead to death typically does not prolong life substantially; a few screening tests may avert some deaths caused by the disease being screened, but even then it is difficult to document an improvement in overall survival.

Ioannidis and his team examined whether screening prevents death in 19 diseases with 39 screening tests, looking at evidence from randomized controlled trials and from meta-analyses combining the results of the trials. Patients were asymptomatic when tested.

In their meta-analysis, the researchers found that mortality from the disease dropped in these cases: ultrasound for abdominal aortic aneurysm in men, mammographyfor breast cancer, and fecal occult blood test and flexible sigmoidoscopy for colorectal cancer. But no other tests reduced the number of deaths caused by the disease in meta-analyses.

What gives?

The test might not be able to detect accurately enough early stages of the disease, or there might not be life-saving treatments available, Ioannidis and colleagues write.

Ioannidis acknowledges that screening might ward off other ill-effects of disease aside from death. But in general, few screening tests among the many new ones being proposed are subjected to a randomized controlled trial before they are introduced, Ioannidis said.

“This is unfortunate. All screening tests should be evaluated with rigorous randomized controlled trials. I see no alternative to prove that they are worth being adopted in large populations,” he told me.

This work follows another recently published paper, in which Ioannidis and colleagues argue that screening all baby boomers for hepatitis C isn’t necessarily beneficial.

Previously: To screen or not to screen for hepatitis C, Bad news for pill poppers? Little clear evidence for Vitamin D efficiency, says Stanford’s John Ioannidis, John Ioannidis, MD: Research’s researcher and Screening could slash number of breast cancer cases
Photo by david_jones

Clinical Trials, Emergency Medicine, Neuroscience, Research

Clinical trial shows progesterone doesn’t improve recovery from head trauma

Clinical trial shows progesterone doesn't improve recovery from head trauma

800px-thumbnailResearchers had high hopes that progesterone, that multipurpose endogenous steroid, could stave off some of the worst effects of head injuries. A quick injection soon after a blunt trauma and  — wa-zam — marked improvement on the widely used Glasgow Outcome Scale, which measures brain injuries on a scale from death to low disability. Or so they thought.

Instead, a nationwide clinical trial was called off after early analyses showed no benefit. The findings were published last week in The New England Journal of Medicine.

“These results are plainly disappointing,” said lead investigator David Wright, MD, an emergency medicine physician at Emory University, in an Emory release.

Stanford, in partnership with Santa Clara Valley Medical Center and the Regional Medical Center of San Jose, enrolled approximately 80 patients in the study between 2008 and 2013, said James Quinn, MD, a Stanford emergency medicine physician. Quinn said there were many benefits to the study even though the results didn’t suggest an improvement.

“The patients all got great care,” Quinn said.  The care teams worked to ensure the care was standardized and top notch for study participants, he said. In addition, there’s still a possibility that progesterone administered closer to the time of injury might help patients. To adhere with study protocols, the teams had to wait one hour after the patient arrived at the emergency room before providing the progesterone or placebo, Quinn said.

The study had a unique design, in part because emergency trauma patients can often not provide consent. Instead, the research team publicized the study before starting and gave participants the opportunity to opt out when they were able.

Quinn also made note of an observation made by he and his colleagues:  Although nationwide most injuries stemmed from vehicle crashes, the Stanford-led teams saw an abundance of bicycle accidents.

Previously: For prolonged seizures, a quick shot often does the trick, study finds, Stanford Medicine story on surviving brain injury wins health journalism award and Estradiol — but not Premarin — prevents neurodegeneration in women at heightened dementia risk
Photo by U.S. Navy

Cancer, Clinical Trials, Events, Stanford News, Women's Health

Country music stars thank Under One Umbrella for supporting Stanford Women’s Cancer Center

Country music stars thank Under One Umbrella for supporting Stanford Women's Cancer Center

7856258414_163d347129_zCombatting cancer isn’t cheap. It takes an innovative team with access to top equipment and support. A team that can provide compassionate care while developing new therapies and scouring through detailed data to uncover unknown aspects of the disease.

At the Stanford’s Women’s Cancer Center, that’s where the Under One Umbrella movement comes in. Now in its sixth year, this group has raised more than $23 million for projects benefitting women with cancer. That money pays for leading doctors and researchers, drug and clinical trials, improved facilities, new treatments, tools and more.

“Your generosity is palpable,” Mark Pegram, MD, director of the Stanford Breast Cancer Oncology Program, told the several hundred donors who gathered at Sharon Heights Golf & Country Club in Palo Alto for the group’s annual luncheon earlier this week. Researchers are making molecular “portraits” of breast cancer to determine which patients would benefit from chemotherapy, he said. They’re testing a treatment that “packs all the punch of chemo, but with no chemo side effects.”

Due to a gift from Sonoma County winery Chateau St. Jean, all of the proceeds from the luncheon were used to support the programs, according to Lisa Schatz, former chair of the steering committee.

During the event, organizers screened a video tribute to Gwen Yearwood, a former patient of the Stanford Women’s Cancer Center, featuring her daughters — singer Trisha Yearwood and Beth Bernard. Then, out came Yearwood and her husband, Garth Brooks to serenade the attendees. “Our family is so grateful,” Yearwood said. “We’re an example of the many families who have benefited from (Stanford) care.”

In appreciation of their service, each donor left the luncheon with a pink umbrella, which came in handy as the Bay Area received much-needed rain in the following days.

Additional information about the group is available on its Facebook page.

Previously: Stanford Women’s Cancer Center: Peace of mind and advanced care under one umbrella, At Stanford event, cancer advocate Susan Love talks about  “a future with no breast cancer” and Don’t hide from breast cancer — facing it early is key 
Photo by 55Laney69

Clinical Trials, Nutrition, Pediatrics, Research, Stanford News

Participant in Stanford food-allergy study delves into lifestyle-changing research

Participant in Stanford food-allergy study delves into lifestyle-changing research

Kari N and patient - smallerWhen I was 10 months old, I was diagnosed with an anaphylactic food allergy to wheat, rye, oats and barley. As I’ve written about in my article, “Pizza and Oreos would have killed me, but they’re now my medicine,” which can be found here, I was always extremely cautious, for only a couple of crumbs could have put me into anaphylactic shock. And over the years, I’ve had my share of scares, involving trips to the hospital and EpiPen injections. My family and I were hoping that someday, a genius researcher/doctor would appear and help do something about food allergies. We finally found that person, and I enrolled in a food allergy study at Stanford led by Kari Nadeau, MD, PhD. Ever since then, my life has changed dramatically.

As I have been a participant in the study for roughly two years now, I’ve never fully understood what has been happening to me. It occurred to me a few months ago that I should probably try to learn about the science behind my food allergy, and how the oral immunotherapy was scientifically changing my body. These changes in my lifestyle were infinite, but how was all of this even possible? Who was behind the scenes, making sure that everything was safe, and okay to be conducted? My brain swelled with all of the questions racing through my mind, so I needed to think of a way to at least try to find out about what was happening to my body.

I’m fortunate enough to attend a school that provides students in their junior or senior year the opportunity to create independent studies. The student designs the curriculum, builds a framework for the class and chooses the best fit teacher to guide the research.

I thought to myself, ‘Why not try an independent study?’ How often is it that students can do research on a project that is directly affecting their life, while simultaneously changing their body? Especially a science project. I kept thinking of ways that I could go about the independent study. I sat with my parents, and asked them about what I should do. They suggested that I write down ten or so questions that I’ve developed throughout the course of the study. And so I did. I brought them in to my science teacher the next day. He looked them over, and we decided to think about ways that we could find the answers to these questions. We scheduled a conference call with the lead doctor of the allergy study at Stanford, Dr. Nadeau.

Kari Nadeau: A mother of five; two sets of twins, and an older boy, proud owner of multiple pets, ranging from rodents to dogs, wife of a brain surgeon and lead doctor of a food allergy study at Stanford. This woman made the time to talk to me, and my science teacher. She is just incredibly organized. Kari explained to us what she and her employees do in the lab at Stanford, and why they do the things they do. I presented my questions, and asked her how I should go about researching them. She graciously invited me to her lab in Palo Alto to meet the lab assistants and get a little taste of what they do. At the lab I could research some of my questions and her mysterious lab assistants could direct me on the path to find answers and plan out an independent study.

I was so overwhelmed, yet so excited. When I get an opportunity like that, I take advantage of it. My parents and I planned the summer and made adjustments so that I could go to Dr. Nadeau’s lab. We figured out a way to make it work.

Continue Reading »

Clinical Trials, Immunology, Research, Transplants

Transplant without lifelong drugs gives patient another chance

Transplant without lifelong drugs gives patient another chance

"DCIM100GOPRO"Imagine learning you have an illness. It’s the same illness that killed your mother. You watched her fade, the last years of her life dreadful to watch, unimaginably tough to endure. The same fate awaits you. Until… it doesn’t. Now there’s a therapy that just might save you.

That’s the story of San Francisco Bay Area resident Cynthia Alcaraz-Jew, featured in the fall issue of Stanford Medicine Magazine. Now in her late 40s, Alcaraz-Jew, like her mother, suffers from a rare genetic condition called Alport Syndrome. The ailment leads to kidney, ear and eye problems.

Alcaraz-Jew didn’t immediately luck out. Her kidneys failed first and her younger brother, Xavier, a perfect immunologic match, offered to donate his kidney. Great news, of course, but a transplant usually means years of immunosuppressive drugs, which leave bones brittle and can lead to infections, heart disease, or even, ironically kidney failure.

Thanks to her perfectly matched kidney, Alcaraz-Jew was able to enroll in a trial led by Stanford immunologist Samuel Strober, MD, that aims to wean transplant patients off immunosuppressive drugs. From the article:

Of the 24 kidney transplant patients with perfectly matched donors who enrolled in the trial beginning in 2000, 16, including Alcaraz-Jew, are living drug free, and three others are working to get off the medications, Strober says. The team is planning to publish a paper summarizing the research results in the near future.

And the photo? That’s Alcaraz-Jew and her husband swimming with whale sharks in Mexico earlier this year.

Previously: Stanford Medicine magazine traverses the immune system, Kidney-transplant recipients party without drugs — immune-suppressing anti-rejection drugs, that is, Might kidney-transplant recipients be able to toss their pills?  and Marked improvement in transplant success on the way, says Stanford immunologist
Photo courtesy of Cynthia Alcaraz-Jew

Bioengineering, Cardiovascular Medicine, Clinical Trials, Research, Science, Stanford News

Using "nanobullets" for good – not evil

Using "nanobullets" for good - not evil

14858598815_b572bddbf9_zMy husband, a big science fiction fan, perked up the other day when I told him I was writing a medical science story about nanotechnology. Apparently, nanotechnology – the study and application of extremely small things – has long been big in the world of science fiction. There, authors have used it to create lots of cool-sounding phantasmagorical stuff like the “nanoprobes” used by the Borg in the movie Star Trek: The Next Generation to assimilate individuals into their collective.

I’m not sure how the fictional nanoprobe was supposedly built, but in my real-life story on the modern day use of nanotechnology to design better methods for heart disease treatment, I do describe the creation of “nanobullets” by Stanford researchers. And it’s pretty cool.

Jayakumar Rajadas, PhD and his colleagues detailed their work in a scientific paper published this month in the journal Biomaterials. Their idea was to create a new and improved delivery system for the delicate peptide apelin into the heart as a treatment for hypertrophic heart disease, which I discuss in the piece:

In a treatment model similar to giving insulin to diabetes patients, physicians have attempted to treat these heart conditions with doses of apelin. The therapeutic agent is delivered intravenously through to the cardiovascular tissue, but due to its short half-life — the drug is quickly eliminated from the blood plasma — the success of this treatment has been limited.

Rajadas considered the possibility for improving the delivery system of the peptide using nanotechnoloy because it has been used for the past 10 years to stabilize therapeutic agents in the body and target them to specific tissues, he said. In this case, the idea was to protect the quickly degrading apelin peptides with large, stable molecules to help transport them to their target organ – the heart:

The research team developed a novel technique to increase the stability of the fragile apelin peptides by protecting them with a lipid cover that Rajadas calls the ‘Trojan Horse’ method of delivery. The liposome ‘nanocarriers’ encapsulates the apelin and sneaks it through the blood to the heart tissue.

The resulting apelin “nanobullets,” as the researchers refer to them, were then delivered through the blood system to the cardiovascular tissue of mice with induced hypertrophic heart conditions. The theory was that the apelin would not be released until it was near the heart tissue.

Researchers then tried it out, shooting the nanobullets into the hearts of mice with hypertrophic heart disease. They delivered two shots over a 14-day period. Results showed that symptoms dramatically improved in the mice that received the shots with the apelin nanobullets when compared to mice shot with saline treatments or even treatments of apelin not protected with the liposome covering.

“Apelin in this form could eventually be used as treatment for humans delivered as a shot rather than intravenously as in the past,” Rajadas told me. “The idea is that regular monthly or bimonthly shots could lesson symptoms.”

Previously: Stanford team develops nanotech-based microchip to diagnose Type 1 diabetes
Photo by NMK Photography

Aging, Chronic Disease, Clinical Trials, Immunology, Research, Stanford News

Is osteoarthritis an inflammatory disorder? New thinking gets clinical test

Is osteoarthritis an inflammatory disorder? New thinking gets clinical test

SM arthritis imageOsteoarthritis sort of comes with the territory of aging. If you live long enough, you’ll probably get it.

For those fortunate enough not to have a working acquaintance with the disease, I describe its onset in a just-published Stanford Medicine article, “When Bones Collide”:

You start to feel some combination of pain, stiffness and tenderness in a thumb, a knee, a hip, a toe or perhaps your back or neck. It takes root, settles in and, probably, gets worse. And once you’ve got it, it never goes away. Eventually, it can get tough to twist off a bottle cap or to get around, depending on the joint or joints affected.

All too many of us, of course, are perfectly familiar with the symptoms of osteoarthritis. An estimated 27 million people in the United States have been diagnosed with it. By 2030, due mainly to the aging of the population, the number will be more like 50 million. Anything so common is all too easy to look at as inevitable: basically, the result of the same kind of wear and tear on your joints that causes the treads on a commuter car’s set of tires to disappear eventually.

But Stanford rheumatologists Bill Robinson, MD, PhD, and Mark Genovese, MD, think that just may not be the way it works. Almost four years ago I wrote about Robinson’s discovery that osteoarthritis is propelled by a sequence of inflammatory events similar to ones associated with Alzheimer’s disease, cardiovascular disease, and type-2 diabetes. That discovery and a steady stream of follow-up work in his lab have spawned a clinical trial, now underway and led by Genovese, to see if a regimen of anti-inflammatory medicines that’s been shown to roll back osteoarthritis’s progression in mice can do the same thing in people.

That’s the kind of progress most of us could live without.

Previously: New thinking about osteoarthritis, older people’s nemesis and Inflammation, not just wear and tear, spawn arthritis
Illustration by Jeffrey Decoster

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