Daily Archives: March 14, 2012

A Conversation with Clay Marsh, Ohio State University

Captured by MD4Utah

Physician-scientist Clay Marsh is one of the indisputable rising stars in the constellation of personalized health care (a term he doesn’t fancy), and a genuine innovator in devising preventative health care as opposed to “sick care,” and in pursuing novel translational research and pilot projects that find new ways to engage patients in the nation’s largest academic health care system.

Among his multifaceted appointments, Marsh currently serves as Executive Director, Center for Personalized Health Care; Vice Dean and Senior Associate Vice President for Research, College of Medicine; Professor of Internal Medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine; and Director, Center for Critical Care and Respiratory Medicine. He is also a member of the National Summit on Personalized Health Care Board of Directors.

Clay Mash, Ohia State University

MD4 Utah:           How would you describe your program’s business model, in particular related to its approach to scientific inquiry?

Clay Marsh:          Our scientific approach and business model are tightly connected. We are trying to save money and improve outcomes, based on foundational principles. One of our primary goals is value innovation:  less cost, higher quality.

MD4 Utah:           How does this approach translate to strategic objectives?

Marsh:                    Essentially, there are three aspects in the immediate-, mid- and long-range. The most immediate goal is to save money through what we call medical hotspotting: coming up with ways to identify people spending the most on health care, and find solutions for them. The top 1 percent of the CMS patients spent 23 to 30 percent of all of the funds in Medicare/Medicaid, the top 5 percent spend 50 percent and the top 15 percent spend 97 percent of the money, so the bottom half, 50 percent spend about 3 percent of the money. If you want a solution that will save money and improve outcomes in a meaningful way, focus on the people spending all the money because focusing on everybody you will really dilute your ability to bring meaningful solutions to the topline.

We are really interested in trying to predict the topline 5 percent of people using the system, utilizing our own health plan as the paradigm there, and then wanting to understand what are the things we can intervene with to improve their outcomes – whether that’s visiting their homes in person, by computer or telephone, looking at their benefits to see if there are medicines that could cause problems or if the medicines could be substituted with other as-effective but less-costly medicines. What are the top diagnoses of these areas: heart failure or something else, for example? We want to really create critical pathways for these diseases, looking at long-term importance and keeping people at home. We think hot spotting would be one of the easiest ways to reduce costs and improve outcomes.

The critical intermediate focus we have is that healthcare delivery is quite variable, so being able to deliver evidence-based practices is not really effective across our whole health system. We need capabilities and to engineer our delivery systems to automatically deliver the right treatments for the right person at the right time. And this has more to do with workflows and systems engineering of medicine practice, as Clayton Christensen said. We really want to create automatic checklist level systems that bring healthcare down from individual physicians to systems that include nurse practitioners and physicians’ assistants and genetic counselors – but many of these would eventually would be pushed down to electronic medical records. The electronic medical record system may be a personal alarm system for each person.

In the long term, we’re working on something not yet ready for prime time: going from disease-oriented care to health- and wellness-oriented care. First we need to understand what health and wellness is. At the end of the day we want to facilitate driving health and health care, not just sick care. We need people to stay well. This will represent an entire paradigm shift in how we look at health and patient care, and knowledge and measurement need to change dramatically.  These three primary goals are connected on multiple levels.

Click here to read more.

Scientists Identify More Than 500 Genes That May Cause Pancreatic Cancer

Captured by Newswise

A global team led by scientists from The Methodist Hospital Research Institute has identified more than 500 genes that may cause or contribute to the development of pancreatic cancer. This particularly deadly disease has a 1-in-20 survival rate after five years, largely because no effective genetic screening method exists for early detection.

Principal investigators Nancy Jenkins, Ph.D., and Neal Copeland, Ph.D., report in the Proceedings of the National Academy of Sciences, online soon, that the vast majority of the 543 genes they identify in mouse models have identical or highly similar versions in humans, and that 20 of those equivalent genes were found to be strongly associated with poor survival in human pancreatic cancer patients.

“Knowing what genes are involved in the development of pancreatic cancer, as well as what those genes’ functions are and how they influence signaling pathways, will be crucial to the development of new drugs and other therapies,” said Copeland, director of the Methodist Cancer Research Program and a National Academy of Sciences fellow.

The scientists show in the PNAS paper that many of the new pancreatic cancer candidate genes are associated with signaling and metabolic pathways that influence cell-to-cell communication, division, and the protection of the cell’s chromosomal DNA, and are therefore plausible cancer genes.

The work described corroborates single-gene work done in humans, and vice versa, and could help people find out whether they are at risk for developing the disease, he said.

The kind of pancreatic cancer the scientists were studying is called pancreatic ductal adenocarcinoma, and is the most common type of pancreatic cancer. Among all cancers, this type of cancer is the 4th deadliest. Only one in four patients diagnosed with this survive a year, and one in 20 are alive after five years.

Jenkins and Copeland emphasize the importance of developing new tools to identify people who at risk for developing pancreatic cancers, so people and their doctors can be more vigilant about the development of the disease, as well as developing biomarkers that can tell pathologists when the disease has begun, and how aggressive it is likely to be.

Click here to read more.

Personalized medicine Dx market exceeded $28B in 2011

Healthcare IT News

Led by tissue tests to aid drug therapy decisions, the personalized medicine testing market exceeded $28 billion in 2011, according to Kalorama Information. The healthcare market research publisher includes in its analysis all tests that are used to determine the appropriate therapeutic on an individual patient.

This broad scope includes new molecular tests based on proven biomarkers, as well as routine glucose and microbial identification tests. The dynamic part of the market is the new tests, and according to Kalorama’s report, “World Market for Personalized Medicine Diagnostics,” the tests that have turned personalized medicine from concept to reality are tissue tests that determine therapy for cancer. These will experience better than average IVD industry revenue growth rates in the next five years.

“Tissue-based diagnostic testing continues to serve as one of the gold standards for cancer diagnosis,” said Shara Rosen, lead diagnostic analyst for Kalorama Information and author of the report. “There is no other technology that can capture the biological context of the disease and the critical parameters that factor into patient outcomes.”

From a biopsy, a pathologist can determine the type of cancer, the stage and the degree to which the cancer has invaded healthy tissue. Personalized tissue-based tests using immunohistochemical stains (IHC) and in situ hybridization (ISH) allow pathologists and researchers to view specific protein and molecular structures in fixed tissues, body fluids, and cells.

To improve patient survival rates, therapies in the oncology marketplace are being combined with predictive biomarkers to help select patients who will respond to specific drugs. The report finds that tissue diagnostics will be in high demand and produce a robust market with many high growth opportunities.

Kalorama reports that the market leaders in what is often called pharmacodiagnostic histology are Dako, Abbott Diagnostics and Roche/Ventana Medical. China Medical is dedicated to making locally produced pharmacodiagnostic histology available.

The report notes that the application of pharmacodiagnostic histology is becoming more sophisticated. Many of these tests are used as companion tests for targeted drugs and also in test services. In addition to the standard IHC and ISH staining procedures, DNA and RNA extracted from tissue samples are further analyzed using mass spectroscopy, PCR and sequencing. As more is understood about radiation therapy, tests have also been developed to assess radiosensitivity of tumors.

USF heart institute may get $2 million from Hillsborough

TBO.com

stephen klasko

2011, STAFF

Dr. Stephen Klasko, CEO of USF Health, touted the economic development aspects of the project.

Hillsborough County is one step closer to becoming an epicenter of genetic research on the treatment for heart disease.

County commissioners voted unanimously Thursday to have the county economic development staff work with USF Health on an agreement that would provide up to $2 million for a heart institute at the University of South Florida. The institute would specialize in using patients’ genetic makeup to create personalized treatment programs.

Earlier this week, the Florida Legislature agreed to include $7 million for the institute in the state’s 2013 budget.

Commissioner Mark Sharpe, who has been working with USF Health officials on the project, said the institute and the products and businesses it spins off will “alter the DNA of our region’s economy.”

“This is the kind of research where there is a definite (economic) value linked to both genomic work and personalized medicine,” Sharpe said after the meeting.

Dr. Stephen Klasko, chief executive officer of USF Health, also touted the economic development aspects of the project. Klasko, a physician who also has a master’s degree in business administration, said he is passionate about “health care transformation that leads to economic benefits.”

“Hillsborough County has the amazing opportunity to be literally the health care solutions county where tomorrow’s health care is happening today,” Klasko said.

The heart institute’s work will revolve around understanding the cellular and molecular mechanisms of cardiovascular diseases and developing personalized, targeted therapies.

Klasko said USF has already invested $7.1 million in cardiovascular research and personalized medicine, plus another $17.3 million on recruiting top professors and researchers in those fields.

USF is working on a partnership with the American College of Cardiology, which has a registry with 15 million patients’ medical records. The registry will be the foundation of a joint investigation to link patients’ clinical information and their electronic medical records to the patients’ biological and blood samples.

The two organizations will then work on translating information from the registries into potential treatments for heart patients.

Klasko said 90 percent of genomic research has to do with science.

Click here to read more.

Patient-centered care ‘flawed’ with consumer focus

Fierce Healthcare

Despite the trend in the catchphrase, “patient-centered care” is a flawed way of putting it, wrote Charles L. Bardes of New York’s Weill Cornell Medical College in a New England Journal of Medicine (NEJM) article, published Thursday.

First coined in 1969 by British psychoanalyst Enid Balint, the term implied taking into account a patient’s social context to deal with illness. Patient-centered care, however, in today’s environment focuses too much on the consumer, Bardes said. The purpose of the patient shifted from obeying to purchasing, now with a strong emphasis on marketing and branding, he explained.

“If the patient is reconceived as a consumer, new priorities take center stage: customer satisfaction, comparison shopping, broad ranges of alternatives, choice, and unimpeded access to goods and services,” he wrote.

Bardes’s position is much like an earlier NEJM article by two Beth Israel Deaconess Medical Center physicians who voiced concerns about industrialized patient care. Pamela Hartzband, assistant professor of medicine at Harvard Medical School, and Jerome Groopman, chair of medicine at Harvard Medical School and chief of experimental medicine at the Beth Israel, described hospitals like “factories” and patient encounters like “economic transactions,” further explaining that the “consumer” term was inappropriate.

However, others see the trend of patients as the focus as undeniable. Patient-centered care could mean simply looking at the individual, perhaps more appropriately (or inappropriately) named “personalized medicine.”

Kent Bottles, senior fellow at the Thomas Jefferson University School of Population Health, said personalized medicine is a trend that healthcare executives can’t ignore, in today’s Hospital Impact blog post. The important trend is personalized medicine that concentrates on the individual not the population, Bottles said. For example, cancer screening by mammography after age 40 in women and colonoscopy after age 50 in men and women does not take into account the different genetic predispositions for breast cancer and colon cancer in individual patients.

As the debate rages on about patient- versus physician-centered care, Bardes suggested a better term that combines the shared investment in care.

“The flaw in the metaphor is that the patient and the doctor must coexist in a therapeutic, social, and economic relation of mutual and highly interwoven prerogatives. Neither is the king, and neither is the sun,” Bardes said. He continued, “Patient and physician must therefore meet as equals, bringing different knowledge, needs, concerns, and gravitational pull but neither claiming a position of centrality.”

Cost of Gene Sequencing Falls, Raising Hopes for Medical Advances

The New York Times

Ramin Rahimian for The New York Times
Complete Genomics has produced more than 3,000 sequences at about $5,000 each this year.

In Silicon Valley, the line between computing and biology has begun to blur in a way that could have enormous consequences for human longevity.

Bill Banyai, an optical physicist at Complete Genomics, has helped make that happen. When he began developing a gene sequencing machine, he relied heavily on his background at two computer networking start-up companies. His digital expertise was essential in designing a factory that automated and greatly lowered the cost of mapping the three billion base pairs that form the human genome.

The promise is that low-cost gene sequencing will lead to a new era of personalized medicine, yielding new approaches for treating cancers and other serious diseases. The arrival of such cures has been glacial, however, although the human genome was originally sequenced more than a decade ago.

Now that is changing, in large part because of the same semiconductor industry manufacturing trends that opened up consumer devices like the PC and the smartphone: exponential increases in processing power and transistor density are accompanied by costs that fall at an accelerating rate.

As a result, both new understanding and new medicines will arrive at a quickening pace, according to the biologists and computer scientists.

“For all of human history, humans have not had the readout of the software that makes them alive,” said Larry Smarr, director of the California Institute of Telecommunications and Information Technology, a research center that is jointly operated by the University of California, San Diego, and the University of California, Irvine, who is a member of the Complete Genomics scientific advisory board. “Once you make the transition from a data poor to data rich environment, everything changes.”

Complete Genomics, based in Mountain View, is one of more than three dozen firms hastening to push the cost of sequencing an entire human genome below $1,000. The challenge is part biology, part chemistry, part computing, and in Complete Genomics’ case, part computer networking.

Complete Genomics is a classic Silicon Valley start-up story. Even the gene sequencing machines, which are housed in a 4,000-square-foot room bathed in an eerie blue light, appear more like a traditional data center than a biology lab.

Click here to read more.

Opinion: On the Gene Patent Debate

The Scientist

Flickr, Brian Turner

Flickr, Brian Turner

The debate over the patenting of technologies related to diagnostic and personalized medicine continues to swell with no resolution in sight. The Supreme Court heard oral arguments in Mayo Collaborative Services v. Prometheus Laboratories, Inc. last December, but has not yet issued a decision.  Just last month, the US Patent and Trademark Office held public hearings to gather information for the “study on genetic testing” that it will use to prepare a report for Congress on this issue. And, the Supreme Court is deciding whether to review the Federal Circuit decision in Association for Molecular Pathology v. Myriad Genetics, Inc. (the BRCAI/gene patenting case), although current speculation is that the Court may defer any action on this case until it issues its decision in Prometheus. While each of these proceedings raises different legal issues, they all relate to the ability to obtain or enforce patent rights on genes, tests, and methods used in personalized medicine.

Personalized medicine is the new frontier of healthcare. It offers the promise of treatments that are tailored to a patient’s individual situation, including the patient’s genetic makeup, the specific variation of the disease the patient suffers from, and the patient’s specific response to a given course of treatment. With personalized medicine, a patient can be given the most effective treatment, improving prognosis and saving considerable time and money on ineffective treatments. As noted on the US Food and Drug Administration’s Pharmacogentics webpage, “[p]harmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose.”

The question being debated is whether these advances are most likely to flourish within the patent system or outside of it.  Do patents promote investment in personalized medicine or stifle innovation by suppressing competition? Do patients benefit from patented therapies, or do they suffer without treatments because they are too expensive? The Founding Fathers established the patent system in the US Constitution as an incentive to “promote the Progress of Science and useful Arts,” but should a different paradigm apply to medical inventions?

Companies working in this field cite the high cost of developing and validating personalized medicine therapies, and emphasize the need to obtain a return on their successful investments. Without the promise of some period of market exclusivity during which they can profit from their years of research, companies will not have any incentive to work in this field—or any resources to do so.

On the other side of the debate, some doctors’ organizations and patient groups believe that the patent system is bad for the healthcare system.  They say that it drives up costs and may prevent patients from obtaining a second opinion, because the patent owner can prevent others from administering patented tests. Many believe that research would continue—at universities and institutions like the National Institutes of Health—and that more people would benefit because the advances would be available on a more widespread basis.

At its heart, this debate may be more of a public policy question than a legal one. People deciding this issue must keep in mind that most university research is funded by government grants and that NIH is a federal agency.  We may want taxpayer money to support this kind of research, but it raises the same specter of big government and taxpayer burden as health care reform. Is a country that may not be ready to provide universal access to proven therapies willing to invest substantial amounts in research programs that may take years to yield any benefits?

Turning back to the law, the US Court of Appeals for the Federal Circuit has refused to draw a line that categorically prohibits patents on personalized medicine. In Prometheus, the court found that methods of optimizing the dose of a specific type of drug was patent-eligible subject matter, not an improper attempt to patent a natural phenomenon.  In Myriad, the court found that isolated DNA associated with an aggressive form of breast cancer could also be patented without violating the prohibition against patents on products of nature because DNA does not naturally occur in an “isolated” form. Although the Supreme Court could reach a different conclusion in either or both cases, its refusal to categorically prohibit business method patents suggests that it may also approach this issue in a similar fashion—cautiously and on a case-by-case basis. That would leave it to Congress to decide if a different approach is needed (such as compulsory licensing as discussed at the Patent Office hearing), or if the current incentives and rewards are striking an adequate balance between private investment and public benefit.

Is Cancer Outwitting ‘Personalized Medicine’?

U.S. News & World Report

The genetic makeup of cancer cells differs significantly from region to region within a single tumor, according to new research that raises questions about the true potential of personalized cancer medicine.

With this treatment approach, doctors study a tumor’s genetic makeup to determine which drugs would work best in a particular patient. But if the genetic mutations driving the cancer cells vary widely, a single tissue sample won’t necessarily give the full picture.

This “targeted therapy” involves “sticking a needle into the primary tumor site and taking a small sliver of a tumor, doing a gene analysis, and creating a genetic profile of the tumor to predict how the tumor will behave,” explained Dr. Dan Longo, an oncologist and deputy editor at the New England Journal of Medicine.

“What this paper tells us is that is an oversimplification of the complexity of tumors and their heterogeneity,” he said. “If you look at different sites of the very same tumor and the very same person, one site might tell you a gene profile associated with a good prognosis and the other site will tell you a gene profile associated with a bad prognosis.”

Longo wrote an editorial accompanying the new study, published in the March 8 issue of the New England Journal of Medicine.

In the study, scientists from Cancer Research UK London Research Institute took 13 biopsies, or tissue samples, from a patient whose kidney cancer had spread. The biopsies were from eight regions of the kidney tumor and four tumors in the chest and lungs.

Researchers also took normal tissue, sequenced the patient’s genome and compared that to what they found in the biopsies.

Genetic analysis turned up 128 mutations in the tumors. But only about one-third, or about 40 of those mutations, were present in all of the biopsies.

“The majority of mutations are not shared in every biopsy,” said senior study author Charles Swanton, a professor of cancer medicine at the research institute.

Swanton and his colleagues also analyzed tumor tissue samples from another three patients with kidney cancer. From a total of 30 biopsies from all four patients, 26 tissue samples had mutations that were highly heterogenous, or varied, from one another.

Some advances have been made using targeted treatments. Tarceva (erlotinib) treats non-small-cell lung cancer by inhibiting epidermal growth factor receptor (EGFR) gene, and Herceptin (trastuzumab) is used to target breast cancers that are human epidermal growth factor receptor 2 (HER-2)-positive.

 

New Alzheimer’s Marker Strongly Predicts Mental Decline

Captured by Newswise

A new marker of Alzheimer’s disease can predict how rapidly a patient’s memory and other mental abilities will decline after the disorder is diagnosed, researchers at Washington University School of Medicine in St. Louis have found.

In 60 patients with early Alzheimer’s disease, higher levels of the marker, visinin-like protein 1 (VILIP-1), in the spinal fluid were linked to a more rapid mental decline in the years that followed.

Scientists need to confirm the results in larger studies, but the new data suggest that VILIP-1 potentially may be a better predictor of Alzheimer’s progression than other markers.

“VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer’s disease,” says lead author Rawan Tarawneh, MD, now an assistant professor of neurology at the University of Jordan. “That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials.”

The study appears March 6 in Neurology.

VILIP-1 was originally identified as a potential indicator of brain cell damage in the laboratory of Jack Ladenson, PhD, the Oree M. Carroll and Lillian B. Ladenson Professor of Clinical Chemistry in Pathology and Immunology at Washington University. Scientists think VILIP-1 serves as a calcium sensor in brain cells. It is released into the cerebrospinal fluid when the cells are injured.

Tarawneh is a former postdoctoral research associate in the laboratory of David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. In an earlier study, she and her colleagues showed that healthy subjects with high levels of VILIP-1 were more likely to develop cognitive impairment and Alzheimer’s disease over a two- to three-year follow-up period.

For the new study, scientists identified patients with very mild or mild Alzheimer’s disease enrolled in studies at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University School of Medicine. At the outset, researchers measured levels of VILIP-1 in patients’ spinal fluid and assessed their mental abilities using an extensive battery of tests. The cognitive function testing was repeated annually.

Click here to read more.

High vitamin D intake may reduce girls’ risk of stress fractures

Captured by Los Angeles Times

Girls who participate in high-intensity sports may reduce their risk of stress fractures with adequate vitamin-D intake.

Girls who participate in high-intensity sports may reduce their risk of stress fractures with adequate vitamin-D intake (Luis Sinco / Los Angeles Times)

Vitamin D may be helpful in protecting highly active pre-teen and teen girls, such as those who play sports, from stress fractures, researchers reported Monday.

The study was surprising because calcium has long been considered the nutrient most vital to bone health in children. But, in developing children, vitamin D intake may matter more.

Researchers analyzed data from 6,721 girls ages 9 to 15 at the start of the study. The girls’ intake of calcium, vitamin D and dairy products was recorded along with stress fractures, which are common sports-related injuries. The girls were followed for seven years.

During that time, almost 4% of the girls developed a stress fracture. Dairy and calcium intake seemed to bear no relationship to the risk of a stress fracture. However, girls with the highest vitamin D intake had a 50% lower risk of stress fracture compared with the girls who had the lowest intake. This was especially evident among girls who participated in at least one hour a day of high-impact physical activity. They had a 52% decreased risk.

Surprisingly, high calcium intake was associated with a doubling of the risk of stress fracture. However, the authors, from Children’s Hospital Boston, said that this “unexpected finding” should be further investigated.

Soda intake did not alter the fracture. The risk was also unchanged when calcium and vitamin D from food only (excluding supplements) were considered.

In 2010, the Institute of Medicine recommended adolescents consume 600 international units per day of vitamin D — up from the previous recommendation of 400 IU per day. Researchers were unable to assess whether even higher levels of vitamin D intake may be more protective, but the question should be studied, they noted.