Published by
Stanford Medicine

Category

Clinical Trials

Cancer, Clinical Trials, Pediatrics, Public Health, Research

Researchers call for broader age limits for cancer trials to increase participation of teenage patients

Researchers call for broader age limits for cancer trials to increase participation of teenage patients

Findings published today in the Lancet Oncology highlight the need to increase the flexibility of age limits for cancer trials so that more teenage patients have access to experimental treatments. “Right now too many of our young patients are needlessly falling through the gap between paediatric and adult cancer trials,” said Lorna Fern, PhD, who led the study and co-ordinates research for the Teenage and Young Adult Clinical Studies Group of the UK-based National Cancer Research Institute.

In the study (subscription required), researchers examined strategies to boost participation of teens and young adults diagnosed with cancer in clinical trials. The study involved 68,275 patients, aged 0-59 years, who were diagnosed with cancer within a five-year window. According to a release:

The study showed [trials designed with broader age limits] led to a 13 per cent rise in 15-19 year old cancer patients taking part in clinical trials between 2005 and 2010 (from 24 to 37 per cent), and a five per cent rise in 20-24 year olds (from 13 to 18 per cent). Children under 14 taking part in trials rose by six per cent (from 52 to 58 per cent).

This rise was due to the increase in availability and access to trials for young people, increased awareness from healthcare professionals, patients and the public about research and importantly the opening of trials with broader age limits which allow older teenagers and young adults to enter trials.

Fern added, “By encouraging doctors to take into account the full age range of patients affected by individual types of cancer, we’ve shown that it’s possible to design trials that include teenage cancer patients and, importantly, that better match the underlying biology of the disease and the people affected.”

Previously: High rates of incarceration among black men could be skewing study results, Stanford researchers examine disparities in use of quality cancer centers and NPR explores the need for improving diversity in clinical trials

Clinical Trials, Nutrition, Parenting, Pediatrics, Research, Women's Health

Stanford study investigates how to prevent moms from passing on eating disorders

Stanford study investigates how to prevent moms from passing on eating disorders

veggie-stirfryResearchers have known for some time that women who have previously had eating disorders face a special set of challenges when they begin feeding their own children: They may unintentionally pass on problematic eating behaviors to their kids.

Now a Stanford research team is studying how to help these moms. They are recruiting families with a child between the ages of 1 and 5 whose mother had anorexia nervosa, bulimia nervosa or binge-eating disorder in the past. In the 16-week study, the researchers will work with both the mother and her partner to build healthy family interactions around food.

From our announcement about the study:

“The data on feeding practices of mothers who have had eating disorders are very worrying,” said Shiri Sadeh-Sharvit, PhD, a visiting scholar at Stanford who is leading the new study. “These mothers are good parents who want only the best for their children, but they struggle with eating-disorder thinking. It’s something that comes and blurs their parenting.”

Prior research has shown that mealtime conflict is more common in families in which the mother has had an eating disorder. These mothers may overfeed or underfeed their children, though underfeeding is more predominant. They also have more difficulty recognizing hunger and fullness cues in themselves and their children, which makes it harder for them to help their kids learn to respond to these sensations. Children whose mothers have had eating disorders are more likely than other kids to be dissatisfied with their bodies and engage in emotional eating, binge eating or restrictive eating.

Sadeh-Sharvit is collaborating with James Lock, MD, PhD, who has a long track record of demonstrating the effectiveness of eating-disorder treatments that involve the patient’s family in the treatment process.

Local families who are interested in participating in the research can contact Sadeh-Sharvit at (650) 497-4949 or shiri_sade@yahoo.com for more information. Stanford’s Eating Disorders Research Program also maintains an online list of all of their eating-disorder studies that are currently seeking participants.

Previously: Promoting healthy eating and a positive body image on college campuses, A growing consensus for revamping anorexia nervosa treatment and Story highlights need to change the way we view and diagnose eating disorders in men
Photo by Indiana Public Media

Clinical Trials, Health Disparities, Medicine and Society, Research

High rates of incarceration among black men could be skewing study results

High rates of incarceration among black men could be skewing study results

prison bars

Few headlines have grabbed my attention like this one did today: “Doctors can’t research the health of black men, because they keep getting sent to prison.” The Vox article focused on a new Yale study that, in the words of writer Dara Lund, “suggests that some of the biggest medical studies of the last few decades may have seriously distorted data on African-American men.”

For the study, researcher Emily Wang, MD, MAS, and colleagues examined fourteen long-term trials that began enrolling participants between 1972-2000. They concluded that the high rates of incarceration among black men at this time (as of 2001, one in six black men had been incarcerated) “may have accounted for up to 65 percent of the loss to follow-up among black men in these studies.” Why is this important? As the researchers describe in the paper, which appears in Health Affairs:

The implications of having a disproportionate number of black men drop out of prospective cohort studies because of incarceration are significant, even though the differences between loss to follow-up are not always large or significantly different between black men, white men, black women, and white women. Conditions such as cardiovascular disease and sickle cell disease are more common in black men than in white men and have complex factors that influence morbidity and mortality. This makes it important for analysts to have access to a large number of cases so that they can adjust for possible confounders.

And:

The likely high association between imprisonment and being lost to follow-up in these studies may yield underpowered and biased estimates for black men. Furthermore, participants who are incarcerated are more likely to be sick than are participants who have never been incarcerated. This difference increases the likelihood that disease rates and progression of disease in blacks and black-white disparities will be underestimated.

One possible solution, Wang and her co-authors note, is for incarcerated people to be allowed to continue their participation in a study. But Lind reports that “for now, there doesn’t appear to be much momentum behind [this].”

Previously: NPR explores the need for improving diversity in clinical trials, Study shows deaths from acute leukemia higher in minority patients, A conversation with Augustus White, a pioneer for underrepresented minorities and Surgeon’s memoir calls for an end to health disparities
Photo by Martin Fisch

Chronic Disease, Clinical Trials, Pediatrics, Research

New research shows how to keep diabetics safer during sleep

New research shows how to keep diabetics safer during sleep

sleeping girlLife with type 1 diabetes requires an astonishing number of health-related decisions – about 180 per day. But patients’ vigilant monitoring of their daytime blood sugar, food intake, insulin and activity levels is perhaps less exhausting than the worries they face about getting a safe night’s sleep. During sleep, diabetics often fail to sense when their blood glucose veers too low. Low blood sugar levels can cause seizures and even, in rare cases, death.

“At night you lose control,” said Bruce Buckingham, MD, a pediatric endocrinologist who treats children with diabetes at Lucile Packard Children’s Hospital Stanford. “It’s when things can happen.” Among children with diabetes, about 75 percent of hypoglycemic seizures occur at night, he said.

That’s why Buckingham and his colleagues across the United States and Canada have been testing various methods to automate blood sugar control during sleep. Our press release on their new research describes an approach that could make a big difference – automated shut-offs of patients’ insulin pumps to keep their sugar levels above the hypoglycemia danger zone:

The new study, which [appeared] online May 7 in Diabetes Care, coupled a glucose sensor worn under the skin to an insulin pump that was connected wirelessly to a computer at the bedside. The computer ran an algorithm that calculated when a low blood-sugar level might occur and then temporarily suspended insulin delivery until the sugar level was trending upward. This occurred without waking the patient. The shutoffs reduced the cumulative time patients spent with low blood sugars during sleep by 81 percent, with only a minimal increase in nighttime glucose levels.

“A system like this should dramatically decrease diabetics’ risk of having a seizure overnight,” said Bruce Buckingham, MD, professor of pediatric endocrinology at Stanford, who led the trial and is a co-author of the study. “Patients and parents will be able to have a better night’s sleep, knowing that there is a much lower risk of severe hypoglcyemia at night.”

During the study, the researchers monitored close to 2,000 nights of sleep in 45 people with type 1 diabetes. The patients, who were 15 to 45 years of age, slept in their own homes and didn’t know ahead of time which nights their insulin pumps could be shut off by the computer and which nights their pumps operated normally. Several measures of hypoglycemia indicated that patients were safer on treatment versus control nights. Morning blood sugar levels were slightly higher after treatment nights, but still within the healthy range.

To get a sense of what the results mean for patients and their families, I spoke with Jack Leguria, whose 14-year-old daughter, Rosa, has had type 1 diabetes for almost 10 years. Rosa participated in the second phase of Buckingham’s research, which is now testing whether the benefits his team documented for older teenagers and adults will extend to children as young as 3. Seeing the new technology in action was exciting for Rosa and her parents.

“This is going to be life-altering for us,” Leguria said. “In four years, Rosa will be ready for college. For a child with type 1 diabetes who is not able to recognize low blood sugar at night, that’s a very difficult prospect for us.”

Continue Reading »

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

The best toxicology lab: a mouse with a human liver

The best toxicology lab: a mouse with a human liver

of mice and menA few years ago, Stanford pharmacogenomic expert Gary Peltz, MD, PhD, collaborating with researchers in Japan, developed a line of bioengineered mice whose livers were largely replaced with human liver cells that recapitulate the architecture and function of a human liver. Now, in a recent study published in PLoS Medicine, Peltz’s team has shown that routine use of this altered lab mouse in standard toxicology tests preceding clinical trials would save human lives.

Among the liver’s numerous other job responsibilities, one of the most important is chemically modifying drugs in various ways to make them easier for the body to get rid of. But some of those chemical products, or metabolites, can themselves be quite toxic if they reach high levels before they’ve been excreted.

The Food and Drug Administration requires that prior to human testing, a drug’s toxicological potential be assessed in at least two mammalian species. But we humans metabolize things differently from other mammals, because our livers are different. That can make for nasty surprises. All too often, drugs showing tremendous promise in preclinical animal assessments fail in human trials due to unforeseen liver toxicity, said Peltz, a former pharmaceutical executive who is intimately familiar with established preclinical testing procedures in the industry.

That’s what happened in 1993 when, after a short safety trial of a drug called FIAU concluded without incident, the comp0und was placed in a phase-2 clinical trial of a drug for hepatitis B. FIAU belongs to a class of drugs that can interfere with viral replication, so it was considered a great candidate for treating virally induced infections such as hepatitis B.

As I wrote in my release about the new study:

“FIAU was supposed to be a revolutionary drug,” Peltz said. “It looked very promising in preclinical tests. In phase 1, when the drug was administered to subjects for a short period of time, the human subjects seemed to do fairly well.” But the phase-2 trial was stopped after 13 weeks, when it became clear that FIAU was destroying patients’ livers.

In fact, nearly half the patients treated with FIAU in that trial died from complications of liver damage. Yet, before advancing to clinical trials FIAU had been tested for as long as six months in mice, rats, dogs and monkeys without any trace of toxicity. An investigation conducted by the National Academy of Sciences later determined that the drug had shown no signs of being dangerous during those rigorous preclinical toxicology tests.

In Peltz’s new study, though, FIAU caused unmistakable early signs of  severe liver toxicity in the bioengineered mice with human livers. This observation would have served as a bright red stop signal that would have prevented the drug from being administered to people.

Bonus item: Using bioengineered mice with human livers instead of mice with murine ones would no doubt result in the clinical and commercial success of some drugs that never got to the human-testing stage because they caused liver toxicity in mice.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Alchemy: From liposuction fluid to new liver cells and Immunology escapes from the mouse trap
Photo by erjkprunczyk

Clinical Trials, Health Policy, Research, Science Policy, Stanford News, Videos

New Stanford center aims to promote research excellence

New Stanford center aims to promote research excellence

Updated 4-24-14: The center founders discuss METRICS in this just-posted 1:2:1 podcast.

***

4-23-14: Stanford has a new center, called the Meta-Research Innovation Center at Stanford, or METRICS for short, that will focus on ways to transform research practices to improve the reproducibility, efficiency and quality of scientific investigations.
When Stanford professor John Ioannidis, MD, DSc, discusses ideas on how METRICS might improve research quality, he points to the wealth of statistics within any newspaper’s sports section.

“Science needs as many ways to measure performance as sports do,” says Ioannidis. “More important, we need to find efficient approaches for enhancing this performance. There are many ideas on how to improve the efficiency of setting a research agenda, prioritizing research questions, optimizing study design, maximizing accuracy of information, minimizing biases, enhancing reporting of research, and aligning incentives and rewards so that research efforts become more successful. Possibly we can do better on all of these fronts.”

The center’s other co-director is Steven Goodman, MD, MHS, PhD, professor of medicine and of health research and policy.

METRICS’s core group of interdisciplinary scholars will be working on various aspects of meta-research, from methodologies to processes to policy. The center will also provide educational funding for students and scholars; organize collaborative working groups that include academics, policymakers, research funders and the public; and help establish similar initiatives worldwide.

You can learn more about “meta-research” and METRICS’s mission in the short interview above and in this release. Ioannidis discusses the center’s short- and long-term goals in the video clip below.

Previously: The Lancet documents waste in research, proposes solutions, “US effect” leads to publication of biased research, says Stanford’s John Ioannidis and Shaky evidence moves animal studies to humans, according to Stanford-led study
Photo in featured-entry box by Norbert Von Der Groeben

Clinical Trials, Research, Science, Stanford News

SPARK program helps researchers cross the “valley of death” between drug discovery and development

SPARK program helps researchers cross the “valley of death” between drug discovery and development

Mochly-RosenSeveral years ago, Stanford neuroscientist Craig Garner, PhD, found himself facing a common problem for researchers: figuring out how to cross the so-called “valley of death” between drug discovery and development. In his case, he wanted to get pharmaceutical companies interested in funding his lab’s promising new Down syndrome treatment.

The answer was SPARK, a hands-on training program that assists scientists in moving their discoveries from bench to bedside. The program was created by Daria Mochly-Rosen, PhD, after she experienced challenges in getting her own entrepreneurial venture off the ground. A story published in yesterday’s Inside Stanford Medicine explains how Mochly-Rosen and a group of industry experts search hundreds of patents submitted to the university’s Office of Technology Licensing and select projects, such as Garner’s, that could benefit from SPARK’s help. My colleague Ranjini Raghunath writes:

Since SPARK’S founding, 51 research teams have “graduated” from the program. More than half of its projects have been licensed or have advanced to clinical use, or both, in sharp contrast to the pharmaceutical industry’s own success rate of approximately five percent. With SPARK’s support, a research team led by dermatologist Alfred Lane, MD, has received a fund- able score on a food and Drug Administration orphan grant for phase-2 trials of a repurposed drug to treat lymphatic malformations that disfigure and disable children. Another team, led by immunologists William Robinson, MD, PhD, and Jeremy Sokolove, MD, is testing a combination of drugs to treat early stages of cartilage loss and joint degeneration in bone arthritis. findings of a third research team led by bioinformatics expert Atul Butte, MD, PhD, and Bruce Ling, PhD — biomarkers for detecting dangerously high blood pres- sure in pregnancy — have already been picked up for licensing by a start-up biotechnology company. Former SPARK beneficiaries, or “SPARKees,” have credited the program with helping them get research grants, publish papers in reputable journals and even land a tenure-track position, Mochly-Rosen said.

The piece goes on to note that universities around the world have launched, or are developing, their own SPARK programs. Mochly-Rosen’s overall goal for the program is to integrate Stanford and other institutions’ programs under one brand and use it to attract commercial investors to support early-stage research discoveries.

Previously: Director of NIH discusses accelerating translation of biomedical research into clinical applications, Re-engineering the drug-development process to speed medical advances, Why drug development is time consuming and expensive (hint: it’s hard) and A glimpse at the price of drugs: Why they cost what they cost
Photo of Daria Mochly-Rosen by Steve Gladfelter

Autoimmune Disease, Chronic Disease, Clinical Trials, Patient Care

Two decades with scleroderma: How I find answers to hard-to-solve questions

The day I was diagnosed with scleroderma 21 years ago was devastating for my parents and me, to say the least. I was 15 years old and I remember thinking: I have what? Scleroderma? What is that? Can you spell that?

Not much was known about the disease and, since the Internet was in its infancy, we couldn’t simply Google “scleroderma” to learn more about it or find support groups. There was no one to bounce off ideas with. My father, who was a diligent researcher, consulted medical textbooks. Meanwhile, my mother, who was born with the “gift of gab,” sought information from anyone and everyone who crossed her path. But ultimately we were forced to rely heavily on doctors’ recommendations, which sadly were pretty gloomy and a bit much for a teenager to handle.

Fast forward to today. When I have a question, I connect with my local chapter of the Scleroderma Foundation, either by e-mailing a board member or by attending a support group meeting. I also go online to the Raynauds Association, Scleroderma Foundation and Pulmonary Hypertension Association. Above all it’s important to find a rheumatologist who is not only knowledgeable about scleroderma, but has a good grasp of its complexities and is willing to help you get the results you need. Trust me – they are out there!

Back in 2004, I decided it was time to get a new rheumatologist. I asked around for recommendations from my personal network and a friend with rheumatoid arthritis suggested I see her physician. Before meeting the doctor, I looked at his online reviews from other patients and his curriculum vitae to get a sense of his academic and professional experience and achievements. When meeting with a new physician, it’s important to ask if she/he has treated other scleroderma patients, gauge their knowledge of clinical trials, find out if they are up to date on the medications being used to treat the different facets of the disease, and make sure they understand the importance of certain annual tests.

When I switched rheumatologists, I had a particular problem I needed to solve. For the most part my illness had become stable, but I had one pesky ulcer that was truly relentless! I tried various calcium channel blockers, ACE Inhibitors, and Vasodilators, and nothing worked. The infections were getting out of control, even though I did my best to stay on top of it. My frustration reached a point where I asked my doctor to “please, remove the first flange of my index finger.” Thankfully he refused and said, “No, we’re not going to give up.”

Continue Reading »

Ask Stanford Med, Chronic Disease, Clinical Trials, Patient Care

Ask Stanford Med: A focus on scleroderma

Ask Stanford Med: A focus on scleroderma

Melissa Warde’s life was forever changed 21 years ago when, at the age of 15, she was diagnosed with scleroderma. At the time, little was known about the chronic connective tissue disease, which involves the hardening and tightening of the skin and fibers that provide the framework and support for the body. “I knew from that day forward, I could sit back and wait for the disease to progress or I could, to the best of my ability, work to control the disease within myself,” Warde said during an Ask Stanford Med Google+ Hangout last week. “I knew I had to have a cheerful disposition, despite the tragedy that I was dealt, and of course having a positive attitude really helped me to focus on the winnings of life.”

During the live conversation, Warde was joined by Lorinda Chung, MD, director of the Scleroderma Center and co-director of the Multidisciplinary Rheumatologic Dermatology Clinic at Stanford, and Karen Gottesman, patient services director for the Scleroderma Foundation of Southern California, for a panel on scleroderma research and progress being made to enhance patients’ quality of life.

Chung opened the discussion with an overview of recent modifications to the disease criteria used in diagnosing scleroderma. Since no two cases of scleroderma are alike, the disease can often be difficult to diagnosis. However, early detection (.pdf) is critical for improving patient outcomes. Under the new criteria, physicians are directed to look for symptoms such as puffy fingers, capillary changes in the nail folds or Raynaud’s disease, which is present in 90 percent of patients with systemic sclerosis. Chung said:

Previously, patients really had to have significant, pretty obvious, skin tightening in order to meet the classification criteria. Or have interstitial lung disease or pulmonary fibrosis, which is scarring in the basis of the lungs, in order to meet the criteria.

These new classification criteria will enable rheumatologists, who may be less experienced in scleroderma, to detect early signs and then refer [patients] appropriately for an accurate diagnosis.

Following Chung’s update on the modifications to the disease criteria, Gottesman spoke about how patients can mange stress related to learning they have a rare, incurable disease and continue living life to the fullest. She advised:

Really learn to be your own advocate. Part of that means educating yourself, not only on all the different aspects of the disease, but also on what type of scleroderma you have so you are aware of possible symptoms that come up.

I think what scares a lot of patients and is really stressful is when you hear of a disease that doesn’t have a cure. But you have to keep in mind that there are hundreds of diseases without cures and we have a lot of treatments in the toolbox to treat the symptoms. At the end of the day you have to learn to co-exist with the disease and that process is really different for every single patient.

Being a proactive patient, Gottesman said, also means being a compliant patient and following through on properly taking any prescribed medications, completing physician recommended tests and other instructions from health-care providers. She said, “If you have a different game plan in mind, then you really need to be upfront [with your doctor] about what it is you need and what you think you want to do, so that you can communicate. That will help you in the long run.”

Continue Reading »

Clinical Trials, NIH, Nutrition, Obesity, Research, Stanford News

Stanford seeks participants for weight-loss study

Stanford seeks participants for weight-loss study

Should diets come in different shapes and sizes? Stanford researchers are exploring that question and are seeking participants for a year-long weight-loss study that aims to understand why people may respond differently to the same diet. Titled “One Diet Does Not Fit All,” the study will examine how factors such as genetic influences and eating and sleeping habits have an impact on a diet’s effectiveness.

From a release:

Participants will be assigned randomly to either a very low-fat or very low-carbohydrate diet for 12 months. They will be required to attend weekly classes at Stanford for the first three months, once every other week for the following three months, and once a month for the remainder of the study. Participants must also be willing to have fasting blood samples drawn four times during the 12-month period and participate in online and written surveys. They will receive all test results at the end of the study.

The study is part of a five-year project funded by the National Institutes of Health and the Nutrition Science Initiative. Following an enrollment last year of 200, this spring researchers hope to enroll at least 135 men and women (pre-menopausal only) between the ages of 18 and 50 who are overweight or obese and are generally in good health.

For a complete list of inclusion criteria, click here. To determine eligibility for this study, complete a brief online survey. For more information, contact Jennifer Robinson at nutrition@stanford.edu.

Previously: How physicians address obesity may affect patients’ success in losing weight, To meet weight loss goals, start exercise and healthy eating programs at the same time, The trouble with the current calorie-counting system, Smaller plates may not be helpful tools for dieters, study suggests and Losing vitamins – along with weight – on a diet

Stanford Medicine Resources: