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Clinical Trials

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

GMA shoot - 560

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

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.

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