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University of Pittsburgh

December 6, 2012

Health Sciences senior VC: Getting health care right

Arthur S. Levine

Arthur S. Levine

“Health care is at an absolute pivotal juncture. It is both the greatest challenge that we face but it’s also the greatest opportunity,” said Arthur S. Levine, senior vice chancellor for the Health Sciences and dean of the School of Medicine, in a lecture last week in the Graduate School of Public Health.

“We have the science now. We’ve got technology that stands ready to serve health care in the most opportune and sophisticated ways, new models that involve redesigning systems and care pathways using large amounts of data, large amounts of science, to personalize medicine,” he said as he discussed the rapid convergence of personalized medicine and health care reform.

“We’ve got to get this right. Because if we don’t get it right it will harm our patients and we will harm our economy.”

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“We can now do more than ever for human beings who are ill. But we still have a gap in all there is to learn about our molecules and cells and, even in the best of animal models, there’s still a gap in our ability to translate what we’ve learned to better the human condition,” Levine said.

“One aspect of that is to understand more about the science behind medical treatment,” he said. “We know that probably not very much more than half of all the things we do as clinicians is actually based in evidence. Much of what we do is based on tradition, based on anecdotes, based on clinical trials that are too limited in scope or not even well designed, Levine said. “A lot of what we do is based on economics and health-care financing.”

Relatively new in the quest for understanding is comparative effectiveness research (CER). “This area of research compares at least two alternatives or interventions, each with potential to be best practices in settings similar to those in which the intervention will actually be employed in clinical practice,” Levine said. “In other words, what actually works and for whom does it work and under what circumstances?”

CER must be guided by the emerging science of genomics, otherwise known as personalized or precision medicine, Levine said.

Clinical trials that compare two options yield a bell-shaped curve that shows most people will do better under one treatment than the other. However, Levine noted, at either end of the curve there are people who either do worse or better than the average. Additionally, there may be people who fare best under the treatment that for most is not the better of the two alternatives.

“The explanation for that has got to be primarily the genome of the people who do better or worse than the average,” Levine said.

“The idea here is to do comparative effectiveness research as a first step and then go beyond that to include genomic and environmental exposure data for all participants in a comparative effectiveness research study in order to understand why some respond to a treatment and others do not.”

Personalized medicine can yield a wealth of information: It can predict susceptibility to a disease or disorder, along with possibly enabling prevention in those susceptible to a particular condition.

For ailments that cannot be prevented, personalized medicine can identify the cause of a disease and design a treatment, tailoring it specifically for each patient.

Genetic analysis also can be used to tailor treatment to a patient’s disease — not concentrating solely on the patient’s genes, but the genes of his or her disease — in cases such as cancer, Levine said.

What we know and don’t know

Humans have some 23,000 genes, with 3,000 of them already associated with a disease or disorder. “That leaves 20,000 genes we don’t know anything about,” Levine said.

The problem may be even more complex because most of the genome does not comprise coding genes. So-called “junk DNA” has been found to contain tens of thousands of regulatory elements, each coded by several genes.

“The genome has become very complex and I’m quite sure we’ll find a disease or a disorder associated with every one of these remaining 20,000 genes,” Levine predicted.

Beyond genes are variations called single nucleotide polymorphisms (SNPs) that increase or decrease risk. Those can be found through genome-wide association studies.

Very rare mutations can be identified using next-generation or deep sequencing. “We’re talking about massive parallel DNA sequencing and aligning the sequences we detect using computational algorithms,” he explained.

“It may require a tremendous amount of sleuthing in large numbers of people and families in order for us to illuminate those rare mutations,” Levine said.

The cost of a genetic sequence has fallen from millions to about $1,800-$2,000 today, he noted, adding that by 2014 sequencing will cost about $1,000 — roughly the same as diagnostic blood testing.

“This is not a panacea for all that afflicts the human condition,” Levine cautioned, citing a recent New England Journal of Medicine paper that showed consumer genome-wide testing did not result in any measurable long-term changes “in people’s psychology, what they ate, whether they exercised or whether they continued to screen themselves for the emergence of a disease.”

And questions remain: Who should have their genome sequenced? And when?

“Even if it only costs $1,000, should we be doing it on everybody?” Levine asked. “Or only on people with strong family histories? Or people who are exposed to certain environments?”

Both health and legal issues come into play. “Once we know what people might be susceptible to, it may influence whether or not they get a job, whether or not they get health insurance,” he said.

Systems biology

And while DNA can be examined, there can be a gap between what the genes predict and what actually happens at the cell, tissue or organ level, Levine said.

“So, we have a tremendous intellectual challenge that goes beyond looking at the genome and that falls into an area called the junction of cell and molecular biology, and a specialty: systems biology, trying to correlate what’s happening in the DNA with what the cell actually does as a consequence of what’s in the DNA.”

Cancer

“Cancer, although we think it’s the low-hanging fruit with regard to personalized medicine, is going to continue to be a tremendous challenge,” Levine said.

“Every tumor has a unique fingerprint of DNA mutation and rearrangement. Tumor-specific changes serve as highly specific markers for detection but they don’t necessarily lead to druggable targets that will allow us to personalize therapy,” he said.

“The story on the molecular level is very complex, complicated further in that tumors are like embryos: The cells divide, the tumor grows, and different genes are expressed and different genes are mutated in different parts of the tumor.”

Pitt research

A former Ford assembly plant just off Centre Avenue is being renovated to house The Center for Innovative Science, an institute focused on personalized medicine. The 350,000-square-foot research building, funded by UPMC, will be complete by early 2015, Levine said. “They are doing that because they think that basically this is a way to improve the quality of patient care and to save money at the same time.”

He added, “UPMC is very focused on using personalized medicine — particularly in cancer, particularly in the aging — in order to improve the quality of life, not make people sick gratuitously and to make the cost of medical care far less expensive.”

Powerful analysis tools are needed to analyze data in order to bridge the gap between what genes predict and what actually occurs in a patient’s body. “We will be spending at least as much time, money and effort — probably much more  — on making sense of what we have accomplished by next-generation sequencing as by doing next-generation sequencing,” he said.

“Right now here we are forming a giant data warehouse in which we are going to take advantage of the fact that all our patients are connected by the electronic health record. We’re going to mine the data in those records. We’re going to add genomic data to that mix. We’re going to add insurance data. We’ll literally have a giant data warehouse — a mega data warehouse that hopefully will serve the best interest both of our patients and the providers of their health care.”

Health-care reform

Levine noted that the United States spends $2 trillion annually — about 18 percent of its gross domestic product — on health care.

“General Motors and Starbucks spend more on health care than they do on steel or coffee,” he noted, adding that health-care expenses also have been the No.1 cause of personal bankruptcy in the United States.

Despite the expense, “among the industrialized countries we’re at the bottom with respect to the outcomes for care of common chronic illnesses” such as cancer, lung disease, depression, anxiety and inflammatory bowel disease.
Although the United States spends about twice as much on health care as other industrialized nations — $8,000 per person each year — “we don’t do nearly as well,” Levine said.

A RAND study has shown that about half of our health care is not evidence-based, Levine said. “A whole lot of it is unnecessary or even dangerous care — that comprises 30 percent of the $2 trillion a year that we’re spending.”

Poor access, due to lack of insurance or proximity to high-quality health care, also is an issue, he said.

Premiums, deductibles and copays are expensive, he said, noting that half of all prescriptions that are written go unfilled “because people don’t have the money to fill them.”

And, Levine said, “In the last month, national figures have shown 8 percent less use of health care than the year before — all over the country.”

Contributing to the expense: “We compensate treatment far more than we do prevention. We also spend a great deal of money on end-of-life care,” Levine said. “We also know that about 75 percent of the total health care and economic burden is due to diseases that are entirely preventable, especially obesity.”

Defensive testing performed by doctors and hospitals fearful of malpractice litigation also helps drive up costs, he said.

Solutions

Levine said health-care reform must:

• Provide universal access — “All people should have health insurance.”

• Reform the insurance market so that legitimate claims are not denied to save money.

• Ensure that patients who have pre-existing illnesses are insured.

• Increase spending on prevention — “at least as much as on treatment.”

• Make solutions heavily dependent on informatics. “We know how to take the medical records of every person in this country, put them in a uniform format and allow them to be seen anywhere in the country,“ he said.

“There is far too much fragmentation and super-specialization in medicine,” Levine said. “Every patient should have a good old-fashioned primary care physician who works intimately with an appropriate team so that the patient simply isn’t shuffled from one specialist to another and as a consequence falls through the cracks.”

• Promote evidence-based treatment: “We should not be paying for any treatment that is not based solidly on scientific evidence,” he said.

Not all care needs to be given by physicians, Levine said. “About 90 percent of health care could easily be delivered by nurses, by dentists, by physician assistants, by pharmacists, to some extent by social workers,” he said. “Physicians have to be in the picture but they don’t have to be the primary caregivers most of the time.”

• Use academic medical centers such at Pitt’s as regional referral centers, he said, noting that regionally integrated systems save money and are more convenient for patients.

Levine also called for the federal government to underwrite the cost of medical education, with graduates obligated to serve the country to pay off their debt.

“That too would solve a great many of the access problems that we have,” he said.

“All of these issues have been addressed to some degree or another by health-care reform, now called Obamacare,” Levine said. “It’s largely health-insurance reform. It mandates that everybody will have insurance or pay a penalty for not having it. … This makes health care a social right,” Levine said.

“The first thing to do, really, was to reform health insurance.

“In subsequent years we believe that it will become a more and more regulated delivery system based increasingly on evidence or people won’t get paid,” he said, predicting that to be seven-10 years away.

—Kimberly K. Barlow

Filed under: Feature, Volume 45 Issue 8

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