In response to recent questioning of the integrity of the dissemination of results in biomedical literature, three medical researchers from Stanford and Duke University are pointing to the need for increased access to data from clinical research.

In a viewpoint article published online today in JAMA Internal Medicine, the authors, Robert Califf, MD, and Jonathan McCall of Duke, and Robert Harrington, MD, of Stanford, write that it’s time for both industry and academia to “catch up to other areas of society:”

The liberation of information once held in secret has toppled regimes and transformed societal expectations regarding progress and possibilities. Access to data from clinical research should be truly democratized.

The goal of clinical research should be to add to the body of evidence that can guide decisions about personal health and health policies, the authors write - but things like selective omission of important findings, inaccuracies in published studies, and the use of unreliable data systems are all hindering this. Harrington and his colleagues outline the critical issues that need to be addressed - issues that concern “(1) the value of the research question, (2) the quality of the execution of the research, and (3) the complete and balanced presentation of all relevant data in the publication” - and sound a hopeful note:

The good news is that powerful tools exist to address and potentially surmount these issues. These tools are the ClinicalTrials.gov registry and the ongoing movement toward data transparency.

ClinicalTrials.gov was originally created to provide researchers, physicians, and the public with ready access to information on clinical trials. More recently, legal requirements to register studies have expanded to encompass the reporting of results, including adverse events, within 1 year of ascertainment of the last primary end point. These requirements are designed to ensure that findings from almost all trials relevant to US medical practice that involve a drug or device are available in a single, accessible public registry. If the requirements of ClinicalTrials.gov and other international registries are maintained and strengthened in areas where they are currently deficient, the benefits should be substantial…

Previously: Research shows small studies may overestimate the effects of many medical interventions, Outing bias in scientific research, A critical look at the difficulty of publishing “negative” results, Examining the impact of unpublished research on medicine and Testing medical ‘truths’

Statistics often don’t tell the whole story. In the case of the Rosebud Indian Reservation in South Dakota, where I traveled last month to write an article for today’s issue of Inside Stanford Medicine, statistics tell a horrifying story. The average life expectancy among the 9,000 residents of the Lakota Sioux tribe is 47 years for the average male, compared to 77 years nationwide. That’s one year younger than Haiti’s 48. Unemployment rates range from 65-80 percent; diabetes, alcoholism and suicide are at epidemic levels.

A group of Stanford students traveled there to spend the week building homes for Habitat for Humanity, volunteering in the Indian Health Service hospital on the reservation, and meeting community leaders in one of the poorest places in the nation. My story describes their experiences:

Each morning, students sat in on the hospital meetings, hearing firsthand the daily struggles of the staff. They heard about the pregnant patient with diabetes who lost her baby the night before, her wails echoing down the hospital halls; they heard about yet another suicide victim, a 25-year-old man who hanged himself two days before. They listened to the staff triaging what levels of care they could afford to provide.

But my article doesn’t nearly tell the whole story. It doesn’t describe the close-knit community on a reservation that has survived a tragic history, the sense of pride and determination among those struggling against the hopelessness that has taken so many young peoples’ lives. One of those Native Americans, Rebecca Foster, PhD, a psychologist at the Rosebud Indian Health Service Hospital, told me about her determination to get an education so that she could return to the reservation to give back. She and her husband are parents to 14 children, seven of them with special needs whom the couple adopted from relatives on the reservation. She talked to me in her office while holding her newborn grandson:

What I tell the young people here is, there is a difference between having to stay here because you are trapped. And choosing to be here because you have something to give. One is a prison, the other is a home… I see a lot of kids who are depressed, who talk about suicide, but they are still resilient. They still have a desire to have a good life, to be happy, to accomplish things. You can never destroy that. There are still a lot of wonderful things on the reservation.

I hope to tell more of these stories in the fall edition of Stanford Medicine magazine.

Previously: Getting back to the basics: A student’s experience working with the Indian Health Service, Lessons from a reservation: Clinic provides insight on women’s health issues, Lessons from a reservation: South Dakota trip sheds light on a life in rural medicine and Lessons from a reservation: Visit to emergency department shows patient care challenges
Photo by Layton Lamsam

Heart disease is the primary cause of death for the more than 20 million people in the United States with chronic kidney disease (CKD). For kidney patients who have secondary diagnoses of coronary artery disease or diabetes, which puts them at particularly high risk of heart attack or stroke, the cholesterol-lowering drugs statins are routinely prescribed.

But for the remainder of patients with chronic kidney disease, it’s unclear whether statin treatment is either cost effective or medically prudent. A Stanford study published today in the Journal of the American College of Cardiology sheds some light on the issue.

…At very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease

“We did a cost-effectiveness analysis weighing the potential benefits in patients with chronic kidney disease and hypertension,” first author Kevin Erickson, MD, a Stanford nephrologist, recently explained to me. “We essentially show that at very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease, but at average retail prices they are only cost-effective in patients with kidney disease who have higher cardiovascular risk.”

The study also indicates that adverse side effects of these drugs, including muscle-related toxicity, and potential diabetes and memory loss, should be taken into consideration by clinicians when determining treatment options. “While statins reduce absolute [cardiovascular disease] risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains,” Erickson and his co-authors cautioned in the paper.

Previously: Wider statin use may be cost-effective way to prevent heart attacks

Research published online yesterday in the New England Journal of Medicine shows a novel anti-clotting drug to be superior at preventing blood clots during coronary stenting procedures compared to the currently used medication.

The study included about 11,000 patients from 153 centers around the world and was led by co-investigators Robert Harrington, MD, chair of the Department of Medicine at Stanford, and Deepak Bhatt, MD, at Harvard. The results of the trial, which were presented at the American College of Cardiology conference in San Francisco yesterday, showed that the drug, called cangrelor, reduced the odds of negative outcomes from stenting procedures such as blood clots, heart attacks and strokes, by 22 percent when compared to the routinely used anti-platelet drug clopidogrel (tradename Plavix).

We need a very potent agent to prevent clotting when we are putting things in the heart artery like wires and stents. We want a fast acting reversible agent, which is why a drug like cangrelor could be useful and why we tested it.

Coronary artery stents are used in the majority of patients who undergo percutaneous coronary intervention (PCI). In the United States, an estimated 600,000 of these procedures are done per year on patients who suffer from coronary artery disease, which causes arteries to become narrowed or blocked.

In our press release, Bhatt comments on why the discovery of a new drug like this is important to patients. He said, “We need a very potent agent to prevent clotting when we are putting things in the heart artery like wires and stents. We want a fast acting reversible agent, which is why a drug like cangrelor could be useful and why we tested it.”

Surgeons practice drilling burr holes during Stanford course

Sherry Wren, MD, a general surgeon at Stanford, has volunteered multiple times for humanitarian missions in Africa with Doctors Without Borders. There, she has treated patients for everything from head traumas to difficult births to gunshot wounds; in the process, she has learned to use hand drills for brain surgery and papaya paste as a salve for severe burns, as well as how to serve as her own anesthesiologist while operating on a patient.

This month, Wren taught a continuing medical education course at Stanford to pass along the skills she learned from these first-hand experience to other surgeons and physicians interested in volunteering for similar medical missions. She recruited experts in neurosurgery, ob/gyn, and other fields to help teach the course, and she drew a large and appreciative crowd of students.

In today’s issue of Inside Stanford Medicine, I describe the course (which she calls a “labor of love”), Wren’s “MacGyver-like skills,” and her ability to “make do” with whichever supplies are available:

Developing countries may not have well-stocked supply closets; there may be no blood bank nearby; anesthesia may be limited; sonograms may be nonexistent.

“We wanted to make physicians understand that it’s all about somehow ‘making it work,’ Wren said. ‘You survive on your wits, making do with what’s on hand.”

…

The course itself was something of a lesson in MacGyver-like inventiveness. Students used pigs’ feet to practice ligament repair. Breech births were simulated from sleeping bags. An orthopaedic company donated thousands of dollars worth of fake bones; hand drills ordered online were used for bone-drilling practice.

Previously: What I did this summer: Stanford medical student works to improve pediatric surgical care in Tanzania
Photo by Sherry Wren

When I first interviewed Brian Kobilka, MD, winner of the 2012 Nobel Prize for Chemistry in October, I was struck by an off-hand comment about his motivation for his near-obsessive two-decades long research quest to uncover the workings of GPCRs, or G-protein-coupled receptors, which serve as one of the main methods of molecular communication within the body.

The research, which it’s believed will lead to the creation of new drugs for clinical care, was not originally done for this purpose. It was motivated by simple scientific curiosity - the kind that often leads to amazing discoveries that help cure suffering or save lives. Initially, Kobilka just really wanted to know how it worked.

In a story published in today’s Inside Stanford Medicine, I describe the success of research based on scientific curiosity in leading to clinical care breakthroughs. The story describes the 30-year history of scientific breakthroughs that led to the approval of a new drug called vismodegib that is used to treat inoperable basal cell carcinomas, and how the drug helped save the eyesight of 101-year-old Winnie Bazurto of San Mateo, Calif. It’s a story that begins with a similar motivation - basic scientific interest - and ends with discoveries that help patients in a very practical way. As Jean Tang, MD, PhD, Bazurto’s dermatologist and vismodegib researcher, says in the article:

If a patient only knew the whole story — how the happenstance of science led to their treatment… If they could go back to when this molecular pathway was first discovered in fruit flies, they’d be amazed. It’s not until the dots are connected 30 years later that it begins to make sense.

Stanford’s Matthew Scott, PhD, one of the key players in this basic-science success story, commented to me in an e-mail just how essential it is for future clinical discoveries that basic science continues to be funded. He expressed concern about a current trend toward conservatism in funding that requires much quicker results that lead to treatment options for patients saying, “Current conservatism in funding asks for translational work that gives cures in a few years (which never happens). Far-sighted funding of basic science … pays off big time.”

The vismodegib story illustrates just how essential basic science is to the future of clinical discoveries:

For many of the basic scientists involved in this research, the clinical use of hedgehog-inhibiting drugs to treat patients like Bazurto — while not the original goal of their research — is the ultimate success.

Previously: Why basic research is the venture capital of the biomedical world, Future of medical research is at risk, says Stanford medical school dean and The economic benefits of publicly funded medical research
Photo by Norbert von der Groeben

A new method of using brain scans to determine whether a patient has chronic lower back pain proved successful 76 percent of the time in a new study from Stanford researchers. The work appears online today in the journal Cerebral Cortex (subscription required), and the hope is this new tool could someday provide an objective measurement for chronic pain, something akin to a “painometer.”

The new method uses advanced computer algorithms to analyze magnetic resonance imaging scans of the brain to provide an objective measurement of chronic pain. While not yet ready for primetime, its success so far makes it appear promising, according to Sean Mackey, MD, PhD, chief of the Division of Pain Medicine and senior author of the study. As he told me for the press release I wrote:

People have been looking for an objective pain detector — a ‘pain scanner’ — for a long time. We’re still a long way from that, but this method may someday augment self-reporting as the primary way of determining whether a patient is in chronic pain.

The need for additional methods for measuring chronic pain beyond the gold standard of self-reporting has long been acknowledged, particularly for the very young and very old who may have difficulty communicating. In a past story I wrote about a similar study by Mackey and colleagues, Hank Greely, JD, a Stanford law professor, said such a tool has the potential to be a “godsend” to the legal system.

Previously: Relieving Pain in America: A new report from the Institute of Medicine, Stanford’s Sean Mackey discusses recent advances in pain research and treatment and Oh what a pain; Stanford scientists work toward developing a “painometer”
Photo by Beautiful Insanity Photography

Two leaders in the battle against the number one killer in the United States - heart disease -have been appointed co-directors of the Stanford Cardiovascular Institute, the nucleus for research and advancements in clinical care for patients with heart disease here.

In a just-posted online story, it was announced that Joseph Wu, MD, PhD, whose work we have previously written about here, and Robert Harrington, MD, chair of the Department of Medicine, will replace Robert Robbins, MD, who left Stanford in November to head up the Texas Medical Center in Houston.

The new dean of the medical school, Lloyd Minor, MD, is quoted in the story lauding the new appointments for the institute, an interdisciplinary organization that includes 500 Stanford basic scientists and researchers:

These two world-renowned researchers bring a unique expertise that will lead the Cardiovascular Institute into the future. Dr. Wu, as an expert in basic science research, and Dr. Harrington, as a leader in clinical trials and population science, will lead the institute on the path toward translating scientific knowledge to improve cardiovascular health for patients.

New research into the causes of heart disease lends credence to the theory that inflammation, seen in plaque buildup in heart vessels, is a cause rather than a consequence of that buildup.

In a study published yesterday in Nature Genetics, an international consortium of scientists, which included researchers from Stanford’s medical school, found fifteen new genetic regions associated with coronary artery disease. The research brings the total number of validated genetic links with heart disease discovered through genome-wide association studies to 46 and takes a significant step forward in understanding the root causes of the deadly disease.

Results of this massive meta-analysis, which included 170 researchers combining genetic data from more than 190,000 research participants, found further evidence for the possible genetic causes of inflammation. This was a key finding because determining the cause of plaque build up in the wall of heart vessels, which causes coronary artery disease, could lead to cures. Stanford’s Themistocles Assimes, MD, PhD, a lead author of the study, commented in my release:

Perhaps the most interesting results of this study show that some people may be born with a predisposition to the development of coronary atherosclerosis because they have inherited mutations in some key genes related to inflammation. There has been much debate as to whether inflammation seen in plaque buildup in heart vessels is a cause or a consequence of the plaques themselves. Our network analysis of the top approximately 240 genetic signals in this study seems to provide evidence that genetic defects in some pathways related to inflammation are a cause.

The new frontier in heart research is sending fruit flies into space to study the effects of weightlessness on their teeny tiny hearts. Spaceflight, apparently, is rough on astronauts hearts, and researchers want to know more about the risks to astronauts who are sent on long space missions.

Peter Lee, MD, PhD, a Stanford heart researcher, came up with the initial plan for the project. He’s been involved with conducting space experiments on muscle atrophy in the past, and it was announced today that he’s the lead scientist of one of eight teams that won a research competition to send their proposed experiments to the International Space Station.

The teams have each won free transportation for their experiments via an upcoming SpaceX Falcon 9 rocket launch from Cape Canaveral Air Force Station planned for December 2013, according to Space Florida, an aerospace development company that sponsored the contest.

The goal of the fruit-fly experiment is to further understand the effects of space travel on astronaut cardiovascular systems, Lee told me. It’s a joint project between Stanford, NASA Ames Research Center and Sanford-Burnham Medical Research Institute, California.

“There appears to be a higher rate of irregular heart rhythms, some decrease in the size or mass of the heart and a little bit of decrease in function of heart after long space flights in astronauts,” Lee said. “It’s not life threatening but very little is known. Fruit fly research is beneficial because they have a lot of the same basic genes and signal transactions at the molecular level as humans.”

Photo by sam_churchill