pwc - impact of personalized medicine

8/8/2019 PWC - Impact of Personalized Medicine

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2010 HealthLeaders Media, a division of HCPro, Inc.

HEALTHLEADERS MEDIA BREAKTHROUGHS: The Impact of Personalized Medicine Today

in collaboration with

2

In the Middle of a

Healthcare has been through an assortment of

global buzzwords that are supposed to create a

convergence of science, healing, and cost-effective-

ness. If the foundations being laid today follow theircurrent course, personalized medicine may indeed be

that disruptor.

BY JIM MOLPUS

The ultimate aspiration of the practice of medicine

is to be truly personalized, with targeted treatments

based on evidence that perfectly fit a patients genetic

markers. Perhaps it is that vision of personalizedmedicine that made it sound intimidating rather than

inviting for many providers.

Personalized

Bridge


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THE BIG PICTURE

In a not-too-distant era in which genomics and proteomics give

a multidimensional map of a patients triggers for genetic reac-

tion, treatment is based on particular science, not general guess-

work. Patients do not suffer through trial and error, or retrospective

medicine. Payers and employers, and the patients themselves, are not

saddled with the bill for countless tests that later prove unnecessary.

Totals may differ due to rounding.

Source: PricewaterhouseCoopers analysis.

Personalized Medicine

Market Size,

2009 and 2015

Roll over each category

to reveal dollar costs.

The potential of personalized medicine belies its current state,

where, in service lines such as pediatrics and cancer, the science has

already moved from bench to bedside. Barriers remain, not the least

of which are reimbursement systems, data, privacy and regulatory

hurdles, and a paradigm shift for how a physician looks at diagnostics.

Proponents believe those hurdles will be crushed by the potential.

2009 TOTAL MARKET:

$225$232 Billion2015 TOTAL MARKET:

$344$452 Billion


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2010 HealthLeaders Media, a division of HCPro, Inc.in collaboration with


THE BIG PICTURE

The cost curve of genetic diagnostics is bending down rapidly.

Kucherlapati says tests that cost $10,000 just a few years ago are now

less than $3,000. Much of the current cost is because genetic analysis

has to be run episodically. When a persons entire genome has already

been sequenced, the underlying data has already been gathered. The

first genome cost $2.7 billion in 1991 dollars.

Now that test is less than $50,000 and with acceleration in

biomedical computing the so-called $1,000 genome is truly near,

Kucherlapati says. Richard Hamermesh, professor of management

practice at Harvard Business School, says the rapidly downward bend-

ing cost curve in genetics is like Moores law on steroids, a reference

to a model in transistor and microchip development that saw their

capacity double every two years.

Healthcare is not a normal market, Hamermesh says. Regulation

creates an impact on growth, he says, and the entire field of diagnostics

has not historically been rewarded at levels comparable to treatment.

But economics is changing that equation.

There is going to be lots of economic incentive to do personal ized

medicine. When half of the drugs that people take dont work, theres a

stake that the payer community has in getting it right the first t ime and

not doing it by trial and error. The barrier remains, Hamermesh says, in

how much it costs to get that information.

Initial investments will have to be madein expanding molecular

medicine capacity or in acceleration of the electronic medical record

decision support.

Personalized medicine is going to revolutionize the practice of

medicine; there is absolutely no doubt about it, says Raju Kucherlapati,

PhD, Paul C. Cabot professor of Genetics at Harvard Medical School

and one of the researchers behind the Human Genome Project.

Implementation of personalized medicine is going to result in better

outcomes for patients, and I truly believe there is going to be reduced

cost. Its happening today, its not some time in the future. This is going

to be the normal practice as we move forward.

Gerald McDougall, principal and U.S. Health Sciences Leader

for PricewaterhouseCoopers, says its no longer a question of if

personalized medicine is coming.

Its how and when those throughout the entire healthcare

continuum will embrace personalized medicine, McDougall says.

Academic medical centers are doing research and development

around molecular and personalized medicine and pushing the

boundaries. What is really compelling right now is that the

technologies and tools for the application of personalized medicine

exist today.

Shifting business model

If viewed in its entirety, the field of personalized medicine reaches

beyond a core of targeted therapeutics and diagnostics to encompasspersonal health record management, disease management, wellness

and nutrition. PricewaterhouseCoopers estimates that the core market

alone accounts for $24 billion in sales now, and will grow 10% annually

to $42 billion by 2015.

Gerald McDougall,U.S. Principal andHealth Sciences Leader,PricewaterhouseCoopers

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THE BIG PICTURE

If youre able to subclassify patient popula-

tions to a better accuracy of therapeutics, the

cost savings associated with that is enormous,

McDougall says. If youre able to get better

information at the individual level to reduce

adverse events, the cost savings is enormous.

Can a Blue Cross Blue Shield or an Aetna say

that some of these strategies related to genetic

risk susceptibility are going to save them cost in

the short term?

No. But we have to be very careful on how we generalize personal-

ized medicine and the personalized medicine strategies because some

of it has massive cost reduction to the system.

Commitment

John Halamka, MD, chief information officer at Beth Israel Deaconess

Medical Center in Boston, says the key to using genomic information

has much to do with automating the routine tasks in medicine, which is

ironically where a lot of medical mistakes now occur.

PatientSite, Beth Israels electronic medical record system, went

live in 2000. It enables, at the touch of a button, appointment making,

medication refills, referrals to specialists, and secure e-mail, so thatdoctors and patients can collaborate together online, Halamka says.

Now, every month, 50,000 patients use it.

Halamka is also personally committed to the success of genomics

in the everyday practice of medicine. He was the fourth person ever

to have had his genome sequenced, and shares his genome, medical

records, and other personal information with the research community

and indeed, the general public, with the idea of taking away some of the

fear patients have about genetics.

Personalized medicine would not be the first shift that asks health-

care leaders to make an educated jump based on current projections of

future reality. Healthcare systems that are going to lead in personalized

medicine can start now, particularly in information technology, says

Dan Roden, MD, assistant vice chancellor for personalized medicine at

Vanderbilt University Medical Center.

It is an absolute given that if were going to execute on the current

vision of personalized medicine, you have to have information technol-

ogy, Roden says. Others, he says, are a commitment to translational

and genome science, as well as a strong commitment to excellence

in clinical care. Institutions that embrace that, and especially at the

leadership level, are the institutions that are going to lead the way in

personalized medicine.

{ }There is going to be lots of economic incen-tive to do personalized medicine. When halfof the drugs that people take dont work,

theres a stake that the payer community hasin getting it right the first time and not doingit by trial and error.

RICHARD HAMERMESH, PROFESSOR OF MANAGEMENT PRACTICE, HARVARD BUSINESS SCHOOL


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6THE BIG PICTURE

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KEY FINDINGS

Source: PricewaterhouseCoopers

Identify health and wellness products and services to

potentially offer to patients

As healthcare moves toward a more patient-centered system,

providers have an important role to play in educating patients

to be co-managers of their health and wellness. But as the

emphasis on wellness grows and consumers seek alternative,

less expensive forms of care, hospital admissions may shrink,

and thus provider systems will have to deliver new clinical

service offerings in order to maintain their revenue flows.

Through better health education with patients, providers can

help raise awareness of and demand for new personalized

therapeutics and diagnostic tests, and thus create new

sources of revenue. A hospitals cancer center, for instance,

could eventually have much of its revenues and margins intherapeutics.

Collaborate in research efforts to accelerate translation

of discoveries from the bench to the bedside

Now is the time for medical research and medical practice

to collaborate to plan together for the practice and

implications of personalized medicine. Such collaboration is

already occurring between oncologists and clinical research

professionals, who are experimenting with clinical trial

pilot projects to accelerate the process of applying research

findings to patients more quickly. These pilots are guiding

doctors to make personalized treatment regimens for cancer

patients. Provider systems should partner with scientists

in personalized medicine who can facilitate collaboration

with research institutes and physicians to translate scientific

discoveries into more effective treatments for patients.

Hospitals that are linked to universities will have an advantage,

as they are poised to take the lead in personalized medicine

research.

Encourage patients to become educated in personalizedmedicine and take steps to advance it

In the new era of individualized care, educational efforts

targeted to patients will help to raise awareness of and

demand for new personalized therapeutics, and thus may

result in new business opportunities for health systems. The

doctor-patient role should evolve from doctors being the sole

source of knowledge to greater emphasis on patient education

to support shared decision-making and choice. Providers

should, for instance, counsel patients on the benefits of

contributing genetic information for research, participating in

clinical trials, using health-oriented social networking sites and

donating biospecimens for bio banks.

Partner with experts in personalized medicine, and

recruit physicians and administrators with expertise in

the field

Personalized medicine is creating a booming market, but

rapid growth of this field is outpacing clinicians ability to

understand it, apply it, or to interpret diagnostic test results.

Providers will have to build an expertise in personalized

medicine if they want to succeed in the new era of healthcare

delivery. Ambitious physicians will educate themselves in

genomics and proteomics, but others will gain knowledge

from experts in the field and recruit physicians and genetic

counselors who can interpret the results of sophisticated

genetic tests and translate them into effective prevention and

treatment strategies. As there are a limited number of genetic

specialists available, this remains a significant challenge

to the progress of personalized medicine. Providers must

communicate the need for greater education in the field of

genomic and proteomic science to medical universities.

Adopt electronic health records, capture genomic

data to populate them, and support industry efforts

to create a system of interoperable EHRs across the

country

There is a vast amount of information being collected in

healthcare databases around the nation, including patient

history, diagnostic reports, clinical research findings, and now

a growing body of genomic data that will explode to billions

of data points on every individual as powerful analytical tools

are developed. The increasing adoption of electronic health

records (EHRs) by hospitals and health systems will increase

the collection of health data exponentially over the next

several years, and bring with it an important opportunity. The

value of the genomic, proteomic, and other health data being

collected becomes greater as it is shared among research

organizations and mined to become more predictive.

But, the full value of EHR systems wont be realized until crosssector interoperability is achieved. Provider systems, payers

and the pharmaceutical industry should work together to

create a new data architecture that will enable interoperability

among IT systems to facilitate the linking and analysis of

health data across the country.


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Now is the time for medical research and medical practice to

collaborate and to plan together for the promise, practice, and

implications of personalized medicine.

The urgent day-to-day pressures of running a hospital, clinic, or

any other health organization leave little time to contemplate what-ifs

and hypotheticals that may occur sometime in the distant future. It

is under this category that many healthcare providers, outside of the

largest academic medical centers, have placed personalized medicine.

From their perspective, exuberance over the science of personalized

medicine exists largely in research laboratories, but it is still a faraway

fantasy as a clinical reality.

In the 145 years since Gregor Mendels work, whose discovery

of inheritance traits in certain plants earned him fame as the father

PersonalizedMedicine:

of the new science of genetics, our understanding of the human

genome and heritable variation has been a long time coming. Yet,

scientific advancement and the pace of innovation have accelerated

exponentially in the past decade. Medical scientists now have

unprecedented insight into how DNA variations can lead to new ways

of diagnosing, treating, and soon preventing thousands of diseases in

all of their sub-classifications.

The practice of medicine will be revolutionized when not only

scientists, but also clinicians and consumers, are armed with

knowledge about the influence of genetic factors on health status and

outcomes. Even more exciting is when that knowledge is used to guide

individual behavior and treatment decisions before, during, and after

an illness occurs.

GeraldMcDougall

Principal,

PricewaterhouseCoopers

LETTER

Many within the healthcare industry are wondering whether personalized medicine has reached the tipping point of

mainstream medicine and at what point it deserves serious attention from clinicians. From our recent conversations with

providers in the U.S. and internationally, we are seeing an excitement and urgency about how to integrate personalized

medicine into a new era of customized care and treatments.

DANATHOMAS

The Time to Act and

Collaborate Is Now


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8LETTER

Personalized medicine is at the core of a larger trend toward

healthcare that is more individualized, predictive, and preventive. The

meaning of personalized medicine to most people implies targeted

therapies and molecular diagnostics, but our definition goes beyond

Framework for Customized Care

Source: PricewaterhouseCoopers

that to embody all of the products and services that provide a

targeted approach to prevention and care. For example, personalized

medicine may be a biologic that targets specific cells or an interactive

technology that allows a diabetic patient and his or her physician to

develop a customized food plan and exercise regime.

For providers, the case for personalized medicine is becoming

more and more compelling in light of the intense pressure they are

under to demonstrate value. Further, major market forces and trends

are driving the need for transformational change in the health system.

Among these trends are the rise of chronic disease, the empowerment

of health consumers, the push for comparative effectiveness, an

urgent need for coordinated care yet decentralized care delivery, and

regulatory and payment reforms that tie reimbursement to patient

outcomes, quality, and efficiencyall of which are working together

to pave the way for a more patient-focused system.

While progress has been made, several key issues need to be

addressed to accelerate the adoption of personalized medicine:

New value creation formulas. Personalized medicine

proponents need to be able to communicate the sciences

long-term value to physicians. And, payers must then develop

incentives to accelerate adoption. Because of the individualized

approach to care, reimbursement decisions may require

subjectivity on a case-by-case basis and far greater collaboration

among payers, providers, and the makers of drugs, diagnostics,

devices, and therapeutics.

Gerald McDougall,U.S. Principal andHealth Sciences Leader,PricewaterhouseCoopers


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9LETTER

Dissemination of knowledge. The rapid growth of this

field is outpacing the ability of patients and even clinicians to

understand it, apply it, or to interpret diagnostic test results;

and, there are a limited number of genetic specialists or

counselors available.

Lack of regulatory pathways for new products. The current

linear, population-based approval process for drug development

and commercialization will be outdated in an era of personalized

medicine. As one of the technologies underpinning personalized

medicine, diagnostics will play a crucial role in its advancement

for their ability to target specific therapies to specific patients

for whom these therapies are known to work. But the current

structure of the FDA is poorly equipped to handle all of the

various individual variations associated with personalized

medicine. The regulatory pathway for the commercialization

of new diagnostics, for example, is unclear due to diversity in

approval pathways and an ongoing expectation of regulatory

reform

IT infrastructure. Personalized medicine will spawn an

exponential increase in genetic, biologic, and metabolic data. Far

more important than the collection of the data for providers is

their informatics competency and data interoperability to enable

coordinated care and broad-based clinical decision support for

individualized patient management.

Personalized medicine will touch the lives of everyone. It

represents a major shift that will ripple across multiple industries and

economic sectors, including ones not traditionally associated with

healthcare. Providers should begin now to peer inside the cradle of

personalized medicine and realize that it holds enormous possibilities

for them and their patients.

Gerald McDougall, Principal, PricewaterhouseCoopers

{ }Personalized medicine is a holistic model of care that examines each indi-viduals unique makeup and designs appropriate strategies for maintainingwellness and treating illness over a lifetime. Our definition of this modelgoes beyond diagnostics and therapeutics to embody all of the products andservices that provide a targeted approach to prevention and care.

GERALD MCDOUGALL, PRINCIPAL, PRICEWATERHOUSECOOPERS


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CASE STUDIESThe Impact ofPersonalized

Medicine Today{

Beth Israel Deaconess Medical CenterNot Just the Genome

The Ohio State University Medical CenterDriving Value

Partners HealthCareCreating the First Waves

Vanderbilt University Medical CenterBuilding the Information Platform


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clinical systems so that you can turn data into information, knowledge,

and wisdom. What we have to do is filter all this data and try to present

it to the doctor or the nurse just in time, when its actionable, when it s

important.

The promise of personalized healthcare goes beyond the technical

knowledge of what each piece of the genome tells cl inicians about a

persons susceptibility to diseases of different types. While the genome

is the glitz and glamour of personalized medicine, its the information

systems and, of course, the clinicians, that are the glue.

Developing an elastic PHRBeth Israel Deaconess, as a health system at the forefront of using

the personal health record (PHR) in patient care, developed its PHR,

PatientSite, in 2000. Some 50,000 patients access their medical

records through it each month, and everything, including clinicians

CASE STUDIES

Beth Israel Deaconess Medical Center

Not Just the Genome

John Halamka, MD, knows a lot about the human genome. In fact,

hes the fourth person ever to have his genome sequenced. But the chief

information officer at Beth Israel Deaconess Medical Center in Boston

still knows that all the genome mapping in the world wont improve

healthcare outcomes, cost, and quality without effective ways to

deliver the huge volume of information contained in the genome to the

physicians who are actually providing patient care. Besides that, theres

a lot more to personalized healthcare than genetic mapping, which is

still in its rapidly developing infancy as far as practical applications to

healthcare outcomes.

His genome, and everyone elses, contains 750 megabytes of clinical

data. Beth Israel Deaconess has the capacity to store a petabyte

thats 1,000 trillion bytesa lot of information. But much of that

information is irrelevant to disease treatment. Clinicians are utterly

overwhelmed by data, Halamka says. So my challenge is to build

Computer-Assisted Communication, Decision-Making, Ties PersonalizedHealthcare Together

BY PHILIP BETBEZE

HEALTHSYSTEMS

NAPSHOT


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CASE STUDIES

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notes as of this year, is there for patients to inspect. The idea behind

sharing this information with patients is to encourage patients and

their caregivers to work together as a team to deliver the best care for

that patient.

Its total shared decision-making and total collaboration, taking

into account patient care preferences, because the doctor and the

patients are on the same team, Halamka says.

PatientSite incorporates a variety of alerts and reminders for

doctors and patients for routine elements of care that are nonethe-

less extremely important to garnering good outcomes. At Beth Israel

Deaconess, those alertsmedication reminders, dosage checks, vac-

cination remindersare tailored to the patients unique demographic

circumstances. The architecture of the system, says Halamka, can

incorporate genomic information as well, should the patient desire it,

and, very importantly, if its relevant.

We do these things based on your age, your susceptibi lity to the flu

or to pneumonia, for example, Halamka says. So a number of things

are personalized, based on sex, age, and what conditions you have.

Further, PatientSite works with vendors such as Microsoft and

Google, which make available free patient health tools directly to

the consumer, to record private data from multiple access points in

the healthcare continuum. If a patient gets all his or her care at Beth

Israel Deaconess, thats great, says Halamka, because everything is on

PatientSite.

But what if you went to the Cleveland Clinic or MinuteClinic or you

have some lab results at Quest and LabCorp or you have data with CVS

and Walgreens? The challenge is you have a very fractured record, he

says.

Through Google Health, for example, patients can pull their datain from all those various sources and then its almost Facebook-like,

Halamka says. The patient can invite his or her clinician into the record.

That kind of interoperability is what the push for EMRs has always been

about, but the promise has until now not matched the hype.

Then what?

At Beth Israel Deaconess, the PHR came last, after seemingly end-

less discussions about how physicians and other clinicians wanted the

data sliced and presented to them, Halamka says. So you come into

the office, and I dont need you to fill out the stupid clipboard for the

umpteenth time, to tell me your medications 27 times, or your allergies

again.

Thats the behavioral aspect of what he sees as two parts of person-

alized healthcare. Then theres the genetic aspect. I know what diseas-

es I am likely to develop, Halamka says of the information he gained

from having his genome mapped. I know my probabilities for disease.

I am twice as likely as the normal human male to get prostate cancer. I

have a mutation in my genome that gives me that risk.

That means Halamka needs prostate exams and PSA tests even

though he is only 48 years old. Now, if my PSA, which is 0.4, came

back as 4.0, that would be something Id better pay attention to. So

personalized medicine, at the genome level, helps you to decide with


EDITORS NOTE


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CASE STUDIES

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theres not going to be an alternative pathway where that disease con-

tinues to progress or express itself.

In the future, researchers are not only going to have to look at what

they think are key genes that are drug targets but will also have to look

at the whole pathway.

So if we block one step, another cork is not going to just pop up

on the other side, Boguski says. He predicts that by 2020, most

everyone will be genotyped shortly after birth in the same way theyre

typed for blood, and that genotype will become a permanent part of

that persons EMR.

By that time, well know enough about the disease gene associa-

tions to predict the kind of diseases you might develop 30 or 40 years

in the future, he says. Its a very exciting time to be able to think

about being able to do that because of the rapid price drop in genomic

sequencing.

The research possibilities of such widespread genotyping are nearly

endless. If, for example, a patient presents at age 35 with a lymphoma,

pathologists will take the cancer genotype, sequence it again, and

compare it against the genotype that person had at birth to tell exactly

which mutations have occurred that have led to that particular tumor.

Thats a precision diagnostic, which will lead to precision, cost-effec-tive therapy, Boguski says.

Decision support

Beth Israel Deaconess PHR system has 2,000 decision support rules,

which include all hematological and oncological clinical pathways.

So today, you dont order a chemotherapy drug, Halamka says.

You order a pathway. If the patient has prostate cancer, for example,

there are five pathways for that disease, which are customized based

on information in that patients PHR. The computer customizes that

pathway based on renal and liver function, among other issues. That

way, we ensure theres best evidence used.

With the personalized pathway, physicians are allowed variation

within reason but dont allow such heterogeneity that each patient

has disparate quality of care. With the addition of the genome, those

five pathways will probably break from five clinical pathways to

perhaps a million.

In breast cancer, for example, its already being done, Halamka

says. Youre doing sequencing of the tumor and then determining

what agent is most effective. And in the future, itll be important in

medications.

Often, medications have a therapeutic index. The difference

between therapy and side effect may be pretty small. But if you

have enough genetic markers, a clinician could say for one patient

the right dose of a certain chemotherapy drug might be 1.2

milligramsthe perfect balance between therapeutic effect and

minimal side effects.

Right now, Halamka notes, every manufacturer says, for the aver-

age human, its 2 milligrams. Just start with that. Some people get

extremely ill from that and some people tolerate it well or get no effect.

Thats where genomics, especially on medication and therapeutics

delivery, will substantial ly change the way we deliver care.

John Halamka, MDChief Information Officer,Beth Israel DeaconessMedical Center



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CASE STUDIES

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Personalized also means personal

Healthcare that is optimal means not only

personalized, but also personal, says Mark

Zeidel, MD, chair of the Department ofMedicine at Beth Israel Deaconess Medical

Center. That means the clinician is still in

charge and can ignore or further refine the

pathway of care that the computer helps

develop for specific patients.

That kind of care requires you, as a physi-

cian, to have a clear grasp of the patients goals

and needs, Zeidel says. Were developing new pathways and targets

all the time. The key is moving that to the general practice of medicine.

Zeidel sees barriers to using the genome effectively in the practice

of care, not only at large academic medical centers that are at the fore-

front of research and technology, but also at smaller community-based

hospitals and healthcare facilities.

You currently can measure for a lot of markers that we think are

important, but you may miss mutations that are important because you

dont have the whole sequence, he says.

Thats why genetic sequencing needs to become inexpensive, but

we need real efforts to be able to process the data. The IT platforms

need to look at this information, process it promptly, Zeidel says.

Currently, the process takes a few weeks. The physician, meanwhile,

has a patient for whom treatment is urgent.

The outcome will be better if they have these custom therapies,

but you have to do something, he says. So the big barriers relate to

cost and rapidity, which will get better over the next several years.

They are not qualitative challenges, theyre quantitative.

Zeidel predicts that because the cost of sequencing infrastructure

is expensive, it will be outsourcedfrom community hospitals, for

exampleand will be done at outside labs. Analyzing the information

will be difficult, but commercial vendors will provide ways for local

clinicians to analyze the information.

Our job is to make our care obsolete every year, Zeidel says.

Were in the business of developing competition for ourselves.

As the technology becomes available to community hospitals,

they will treat common diseases and academic centers will develop

approaches to treat patients with rare and difficult diseases.

{ }So if we block one step, another cork isnot going to just pop up on the other side.Boguski predicts that by 2020, most everyone

will be genotyped shortly after birth in thesame way theyre typed for blood, and thatgenotype will become a permanent part ofthat persons EMR.

MARK BOGUSKI, MD, DEPARTMENT OF PATHOLOGY, BETH ISRAEL DEACONESS MEDICAL CENTER

CASE STUDIES


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18CASE STUDIES

The Ohio State University Medical Center

Driving Value

18

But what is personalized healthcare? Some hear the term and thinkimmediately of genome mappingfiguring out a persons proclivity to

come down with any number of diseases based on heredity. Turns out

thats only a small part of what Marsh means by personalized health-

care, and a part that, with few exceptions, is not ready for a large-scale

rollout.

First theres the challenge of figuring out what the genome says

about a persons susceptibility, but second, and most importantly, what

modern medicine can actual ly do about it. Marsh and OSUMC have a

more expansive definition of personalized medicine, and its challenges

are less those of pure science and more those of money, patient partici-

pation, and clinical pathways that are evidence-based.

One of the challenges in personalized medicine has been defining

what you mean by it, he says. The Center for Personalized Health Care

CClay Marsh, MD, isnt alone when he calls healthcare delivery in

this country, fundamentally broken. But where he differs from all the

naysayers is that he thinks he and his institution can be a part of doing

something about that. Certainly the lack of centralization and precision

in what we do in medicine would generally equate to failure of most

other business sectors, he says.

So what does that have to do with so-called personalized

medicine? A lot, it turns out. Marsh, in addition to his role as vice

dean of research with the Ohio State College of Medicine, is executive

director of the Center for Personalized Health Care at the Ohio State

University Medical Center (OSUMC). While he doesnt necessarily see

personalized medicine as the latest silver bullet that will eliminate

waste and harm in healthcare, he thinks it can go a long way toward

achieving that goal.

Can Personalization Drive Better Value in Healthcare?

BY PHILIP BETBEZE

HEALTHSYSTEMS

NAPSHOT


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Moving from disease treatment to health treatment

Developing a personalized medicine model that works in the real

world means integrating genomics with the delivery of healthcare,

Marsh says. Its actually taking evidence-based medicine to a different

level, he says, because its not just evidence-based medicine, its trying

to automate the delivery of that medicine on an individual basis.

The first level of personalized medicine, which Marsh says is achiev-

able today with discipline and culture change even outside of academic

medical centers, is to standardize the way medicine is practiced, and to

create a more automated system that would be active irrespective of who

is supervising the care of the patient. The Center for Personalized Health

Care at Ohio State depends heavily on automated, closed-loop, opt-out

practice pathways using information technology and other computationaltools to push best practices to the physician in charge of a patients care.

We shouldnt ask physicians to choose to activate them. Instead we

should make them an automated response in our safer, more standard-

ized system, and allow physicians or other professionals to opt out if

they dont think they are correct for a particular patient, he says.

Measurement of adherence to the pathways ingrained in the way

the electronic medical record talks to the preloaded systems of care

for a patient is key to reducing variability and mistakes, Marsh says.

In many ways, the doctor is still the hierarchical leader of the medi-

cal team and practices whatever way he or she feels is important, as

opposed to having a commitment to creating and executing this auto-

mation like autopilot in a plane, he says.

Our focus is to standardize what we do to reduce the variability in

practice and make sure that if we know somethings good to do, that we

execute it seamlessly, and we execute it all the time, no matter where we

are, no matter who the doctor is in the environment. The environment

itself is actually part of the protection.

Thats a step that most hospitals and healthcare providers have not

made because its technically sophisticated on the IT front. Marsh says

its also a culturally sophisticated step, because it requires us to say

that in this cockpit management kind of scheme that were not trying

to serve the pilot, were trying to serve the passengers.

Its already here, in dribs and drabs

Steven Gabbe, MD, the CEO of The Ohio State University Medical

Center, says personalized healthcare is already here, but far from per-

fected. He uses the example of diabetes, from which he suffers.

Ive had diabetes for over 40 years, so I really had a chance to

experience the changes for people with diabetes from a limited num-

ber of options and a limited amount of flexibility, to a point now where

thanks to scientific and technological advances, we have remarkable

ability to personalize the care of people with diabetes.

Gabbe, offers the example of blood glucose meters, which are taken

for granted now, but werent available until about 1980. He personally

uses a more advanced continuous glucose sensor, which monitors ones

glucose levels throughout the day, during exercise, work, and sleep.

Further, we have a variety of new insulins that can be used to tailor

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treatment to ones diet, and activity. So these advances allow each indi-

viduals lifestyle, diet, exercise pattern, and work schedule to be accom-

modated, Gabbe explains. Personalized medicine of a sort is also key to

taking care of OSUMCs employees. Personalized health assessments

are done for each of its employees, and then lifestyle modification

diet, and healthcare, and coachingare prescribed so they can improve

their health. This, of course, helps us in our goal to be a workplace

of choice, which is one of our strategic objectives, and helps us get a

return on that investment very quickly.

Currently, through some basic genetic testing, Ohio State is able to

assess therapy for people who may be on warfarin, an anticoagulant, by

using their genetic information to prescribe the best dosage for them.

Further, simple tests can determine whether certain individuals can be

treated with certain chemotherapeutic drugs for certain types of colon

cancer, Gabbe says.

I think it relates to about 5% of colon cancers, but when you think

about that across the country, thats a lot of people. He sees further

promise as health risk assessments mature, as well. By developing a

genetic database and a patient database and linking those, well begin

to discover new opportunities to use genetics for therapy and risk

assessment. More expansion of our genetic knowledge will allow us to

rapidly and inexpensively screen individuals as part of their assessment,and use that information for risk assessment, lifestyle interventions,

and therapy. Thats going to grow over the years.

Potential

The second leg of a three-legged stool upon which personalized


healthcare theoretically stands, says Marsh, is what most people

associate with the term genetic markers and how those markers can

be used to tailor therapies. But the genome doesnt always provide

clear answersat least not yet.

Most diseases are what we call complex diseases, meaning, there

are multiple different elements that actually come together to either

have you experience something youre at risk for or not, he says. So

you may have a genetic element that says that youre predisposed to

cancer, but that doesnt necessarily mean that you will get it.

For example, there are genetic markers that help doctors obtain a

picture of risk for breast cancer. But to consider doing something as

traumatic and highly interventional as preventive bilateral mastecto-

mies, for example, much more information is needed, because perhaps80% of people with that marker will get the disease at some point, but

20% dont.

So why does that 20% not get it? he asks. Or if you look at smok-

ers, 15% of people might get lung cancer or chronic lung disease, but

85% of people dont. So understanding why, even though you might

have the same genetic risk, some people progress to a disease and

other people dont, is really important.

Developing that snapshot of an individuals health risk at a three-

dimensional level based on genetic information, environment, and a

number of other variables is really the cutting edge of research, which

is still in the experimental and data-gathering stage, says Marsh. Thats

not to say that many personalized medicine constructs arent ready for

prime time now.

Clay Marsh, MDExecutive Director, Center forPersonalized Health Care,The Ohio State UniversityMedical Center



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goal is one where not only does the healthcare system care for patients

better when they have the onset of any sort of complications through

opt-out clinical pathways, but to offer patients predictive data to help

them modify their behavior or environment before they have the onset

of something for which they have a proclivity.

Being able to look at that data and look for trends is a very com-

putational and data-intensive process that is a throughput challenge

from an IT perspective, Teater says. To sift through that information

manually is clearly impossible. Theres way too much of it. So you have

to have electronic processes to start to understand some of these rela-

tionships between data.

She uses herself as an example. I had surgery a few years ago,

and had a complication with a blood clot. At the time, through trial anderror, they discovered that I am resistant to blood-clotting drugs. It

takes an inordinately high dose for clotting drugs to work on me. If I

were able to provide that information through the EMR to the physi-

cians that were taking care of me up front, they would have known that

out of the gate, and it may have helped them make decisions in a differ-

ent way that would have made my clinical progress move along a little

faster. Certainly its in my medical record now.

The key to providing that information for patients who havent

experienced surgery before, for example, would require taking some

of the information gleaned from patients who are enrolled in OSUs

research studies, and load those markers into our EMR so that we can

provide that additional information to our clinicians as they make deci-

sions, says Teater.


The building of each of those individual rules is a labor-intensive

process, because there is no opportunity to make mistakes. It has to

be supported by widely accepted evidence that there is a link between

these two pieces of information, she says. In the end, it is still a physi-

cian making care decisions for their patients, but that is extra informa-

tion for them.

Standardization of care

Standardization of our care models and execution of evidence-based

practices, in a more low-variability way is one way to achieve the prom-

ise of personalized medicine, says Marsh. Certainly providing access and

help to people with chronic disease who are spending a lot of the health-

care dollar and preventing chronic disease is a low-hanging fruit that

could be harvested. But to fundamentally benefit people and transformthe way we do things, we have to think of a much greater and deeper

ecosystem change that needs to made in medicine, he says. Just like

our car maintenance, we wouldnt drive our cars until the red lights

come on, and drive them even more until they break down on the side of

the road, and then call somebody to get it fixed. We would spend money

to try to prevent them from having problems. Clearly thats not the way

that healthcare is delivered, nor is it the way its currently reimbursed.

We need fundamental change that integrates the whole system,

and provides tools and capabilities to really empower people in a differ-

ent way, he says. Were working with a lot of outstanding partners to

tr y to come up with some of those solution sets, and to figure out how

to apply them in ways that are meaningful, compelling, less expensive,

and higher quality using the principles of P4 Medicine.

Steven Gabbe, MDSenior VP for Health Sciences, ChiefExecutive Officer, The Ohio StateUniversity Medical Center


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2424CASE STUDIES

Partners HealthCare

Creating theFirst Wavesendocrinologist, says that warfarin has a relative narrow therapeutic

index, meaning that not giving enough anticoagulant and giving toomuch is a small window. And the consequences of a misdiagnosis

are dire, including stroke. There are two gene products, two proteins,

that have a major impact on how you metabolize warfarin. Within

those gene products, there are six genetic variants in the protein

that metabolize the drug and three genetic variants in the targeting

of the drug, meaning there are 18 possible variants that affect the

metabolism and target response, Freeman says.

So what the study did was to try to understand that, if you knew

the genetic variants, could you come up with an algorithm for treat-

ment that would alter the dose of warfarin that would provide them

better anticoagulation control, Freeman says. Initial results of the

study, which is not yet published, found which variants needed more

medication and which ones less.

RResearch into personalized medicine rotates around a classic

conundrum: To find the science and evidence behind a particular, indi-vidualized therapy that can be called personalized requires a large

pool to be narrowed to a very small one, and then to one person.

To find the relatively few people who may deviate from the

norm may mean testing a larger group. So researchers at Partners

HealthCare, the combination of Brigham and Womens and

Massachusetts General Hospital and the major teaching affiliates of

Harvard Medical School, are exploring a multi-structured approach to

make personalized medicine turn from science to practice.

Mason W. Freeman, MD, director of the Translational Medicine

Group at Massachusetts General Hospital, is leading a clinical trial

in partnership with the FDA to understand how certain people with

a defined list of genetic variations respond differently to commonly

used blood thinners such as warfarin. Mason, an internist and

BY JIM MOLPUS

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There are a couple of things that are absolutely spot-on central to

the whole issue of personalized medicine, says Freeman. For probably

two-thirds of the potential genotype variants, you dont need to change

the dose. But in the third, where they have a more atypical variant that

has a bigger impact on the warfarin dose, then you do change the dose

quite a bit.

So early results are clearly showing that for those patients

with the atypical variant, physicians get much better control of their

anticoagulation therapy when they use the genetic information,

Freeman says. To understand who has the variant requires a s ingle

$400 genetic test, Freeman says. But for the two-thirds of people in the

study who were not in the atypical variant, the test did not alter treat-

ment. Now you have the classic conundrum of personalized medicine

for a lot of conditions, Freeman says. Are you willing to pay to have

everybody have it done to benefit a third? The issue may not last long,

as the so-called $1,000 genomei.e., the entire sequence at once

may only be a few years away.

Everything changes in this equation on the day that whole

genome sequencing is now part of your medical record because youve

got all of the gene variants already in the computer, done with one

test, says Freeman. So its not a per-condition gene test. Once you

pay $1,000 or less to have it in your computer system, you have everyvariant that they have for every disorder that you would ever have a

genetic relationship to. Its incredibly cost-effective.

Next meaningful use

John Glaser is helping to build two information technology

infrastructures to create the framework for personalized medicine.

The first is as chief information officer at Partners, where he and

his team are building the IT vision to fit the goals of the Partners

HealthCare Center for Personalized Genetic Medicine, which include a

robust electronic medical record, personalized genomic data available

for clinical use, and physician access to electronic decision support

tools. The second is as senior advisor to David Blumenthal, MD, the

federal coordinator for healthcare information technology, in the devel-

opment of meaningful use definitions under the HITECH provisions

of the American Recovery and Reinvestment Act. In a national sense,

the hope is to lay the foundation for the decision support that will be

needed for personalized medicine, but to get there will mean taking

some first steps.

When I look at the standards that have come through the interim

final rule and the definition of meaningful use that is currently in the

notice of proposed rulemaking, it is very fundamental, Glaser says. Its

things like a code for a lab test and e-prescribing. And theres nothing in

the current definition that includes personalized medicine. But theres

also nothing being done there that will make personalized medicine

harder over time.

It wont necessarily be too far along before those rules may come

into future definitions of meaningful use, Glaser says. Maybe well see

in 2013 and 2015 definitions of meaningful use and in standards in the

years to come that are more dead center to personalized medicine,

he says. But were laying a foundation that the personalized medicine

revolution will be able to leverage and frankly will be necessary,

Partners HealthCare

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because in the years ahead,

the sheer amount of decision

support will require an EHR

foundation.Before that decision

support can be actualized, some

connections in research have

to be made. Partners is leading

on multiple research fronts,

particularly on the software

that is necessary to merge EHR

and genetic data in biomedical

computing, which is why National

Institutes of Health Centers

Informatics for Integrating

Biology and the Bedside resides

at Partners.

In the clinical areas, Partners

has already begun to deploy

genetic-related decision sup-

port. One of the challenges that

Partners found isnt necessarily in

getting the data to physicians, but

rather getting the results in ways physicians can process. A cryptic set

of raw results is not useful

to todays physicians.

A lot of clinicians dont know how to interpret genetic results,

Glaser says. They know how to look at a graph of chemistry results .

Partners HealthCare

They know how to read a pathology report. But they actually dontknow how to look at this data and to make decisions based on it.

Partners has developed software called Patient Genome Explorer,

which pops up in the genetic results a physician sees for treatment

decisions and explains what the data mean in treatment terms.

Another program, GeneInsight creates a report for the patient and

Functioning of the Information Technology Infrastructure

Source: Partners HealthCare

Physician

Bioinformatics

Testing Platform

ElectronicMedical Record

Geneticist/Genetic

CounselorGenomic VariantInterpretation Engine(GVIE) and GeneInsight

Manage interpretation oftest results

Clinical SecurityContext

Manages storage and securityof structured genetic/genomictest results

Gateway for IntegratedGenomics-ProteomicsApplications and Data

Manage physical aspects of thetesting process

Genetic/GenomicTesting

MolecularDiagnosticLaboratory

Mason W. Freeman, MD,Director of the TranslationalMedicine Group,Massachusetts General Hospital


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referring physicians that describes the genetic variance and possible

ramifications for treatment. Like any decision support tool, the ones

at Partners are only as good as their data, and even in the relatively

new field of personalized medicine must be kept in line with current

evidence.

One of the other challenges, and you see this in cancer, is that our

understanding of what a gene mutation meant five years ago has been

replaced by more knowledge that has come through, Glaser says. So a

prior result might have led you to do X. Now the research may want you

to do something different than X. So if you have a patient under your

care and all of a sudden we have new understanding, we need to tell

you that because the course of treatment needs to change.

Community next

Although the wave of personalized medicine is roll ing from academic

medical centers to community hospitals at a fast pace, Glaser says the

wave wont wash up on all shores at the same time, with particular

areas such as cancer already being a service l ine in which community

hospitals may enter the translational science. Rather than being a

threat, embracing personalized medicine may be an opportunity, says

Partners HealthCare

Raju Kucherlapati, PhD, Paul C. Cabot Professor of Genetics at Harvard

Medical School. Estimates are that only 15% of cancer patients nation-

ally receive their treatment at premier academic medical centers, with

the rest receiving care at a community hospital or oncology center.

Even at the academic medical centers, different levels of personal-

ized medicine are being applied, Kucherlapati says. In the community

setting, it is widely variable. There are probably a few practices that

practice some level of personalized medicine, but many of them do not.

It is still a big challenge and an opportunity to get all of these communi-

ty oncology practices to embrace these ideas of personalized medicine,

because for the first time, if they do embrace it, they have the oppor-

tunity to provide the kind of care that major academic medical centers

would be able to provide.

Glaser advises that even a medium-sized community hospital

should start to look at whether its clinicians are studying or engaged in

personalized medicine, especially in cancer. Its also worth asking your

EHR vendor what their plans are for personalized medicine, Glaser

says. Meaningful use may be more of an immediate agenda item. But I

wouldnt lose track of those things and would expect that I may need to

respond to personalized medicine in the near-term.

John Glaser,Chief Information Officer,

Partners HealthCareHaving trouble listening?Click here.

{ }A lot of clinicians dont know how to interpret genetic results, Glasersays. They know how to look at a graph of chemistry results. They knowhow to read a pathology report. But they actually dont know how to look

at this data and to make decisions based on it.JOHN GLASER, CHIEF INFORMATION OFFICER, PARTNERS HEALTHCARE

2828CASE STUDIES BY JIM MOLPUS


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2828CASE STUDIES

Vanderbilt University Medical Center

Targeting Decision Support

The first recognition is that genetic variation, the minute differenc-

es between you and me constituting less than 1% of our DNA blueprint,

can strongly predict in some cases whether we will get a good result

from a medication or a bad result, Masys says. He explains that VESPA

will work like 1.9 million experiments of nature by combing de-iden-

tified data of treatments and reactions stored from those treated at

Vanderbilt, plus the data from BioVU, a de-identified DNA bio bank that

stores leftover blood from 80,000 individuals treated at Vanderbilt.

(Patients sign a consent form for the use of leftover blood.)

The idea is to use the electronic medical record to find a group of

individuals who got a medicine and got a good effect, and then another

group who got the same medicine and got a bad effect, and then go to

the DNA and do a genomewide scan to see whether we could have pre-

dicted, based on minute variations in the DNA, whether one group had

a different pattern than the other, Masys says.

TThe hope of the American Recovery and Reinvestment Act (ARRA)

was to build the infrastructure for future innovation and commerce. For

retail and construction , the future is built on highways. For personalized

medicine, the paths are the data points in an electronic health record

that store those few genetic differences that separate a personalized

care plan.

In 2009, Vanderbilt University Medical Center in Nashville

launched VESPA (Vanderbilt Electronic Systems for Pharmacogenomic

Assessment), a $6.4 million research grant sponsored by the National

Institutes of Health under its Grand Opportunities program using

ARRA funds. The program tries to blend new science with some of

the vision and potential use of personalized medicine, says Dan Masys,

MD, coprincipal investigator of the VESPA program and chair of the

department of biomedical informatics at Vanderbilt University Medical

School.

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Vanderbilt University Medical Center is building off of its history of innovationin informatics to bring personalized medicine to physicians when they need it.

BY JIM MOLPUS

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But the idea behind VESPA is not to stop at bench science, but

to make a quick leap into the clinical realm. Once weve found those

patterns, the normal way is you just publish a scientific paper in the lit-

erature. Thats the way that science generally runs, but thats not what

VESPA is proposing to do, says Masys. VESPA is proposing to take

that information back into the clinic through patient-specific computer-

ized clinical decis ion support so that we could have, in essence, a small

panel of genotypesthat is, small points of variation in your DNA

that we would just go ahead and capture ahead of time on everyone

who walks through the door. So that information would already be

there at the point where some fraction of people will have a doctor pre-

scribe a medicine that theyve never been exposed to before, for which

we know DNA variation predicts a different response.

Masys and his team hope to get the results of VESPA into

Vanderbilts EHR within a year to 18 months, at which point the infor-

mation will be available to physicians at the point of care. That, says

Masys, is a true acceleration of the promise of personalized medicine.

There is a little bit of this occurring out there already, and its been

called personalized medicine, but its all after-the-fact personalized

medicine. Its after the doctor has already prescribed the medicine,

Masys says. So in a sense, the moment has passed where the infor-

mation is important. And so were proposing to move this ahead and

formally evaluate how much additional improvement in care results

from the DNA information compared to the way we normally make our

clinical decision.

The way personalized medicine works in clinical practice today

is typically too slow to be effective, says Dan Roden, MD, coprincipal

investigator with Masys on VESPA and assistant vice chancellor for

personalized medicine at Vanderbilt.

Theres no question that personalized medicine is not in wide-

spread clinical practice, not at all , Roden says, because the typical

patient-physician encounter is built around a diagnosis based on clinical

factors, a treatment decision made by the doctor, and communication

of both to the patient.

If at the end of that discussion I have to turn around and say,

Oh, and by the way, your response to that drug is influenced by genetic

factors, and that test will be available maybe tomorrow, but it s more

likely a couple of weeks. And Ill call you up when we have the result.

And I might tell you youre on the right dose of the right medicine. I

might also tell you youre on the wrong dose of the right medicine.

I might tell you youre on the wrong medicine.

Its hard enough to explain to people that they need to go on this

new medicine and why. But then to turn around and say, Oh, and by

the way, were going to have this whole discussion again in a couple of

weeksI dont exactly know when? Its just way too cumbersome.

Cost behind the science

Although the VESPA study is built on a research grant, Vanderbilt is

concurrently tracking the data for cost analysis with its Institute for

Medicine and Public Health. It is that type of data which will build the

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with the computer rules and algorithms will be able to actually reason

with your entire genome once that becomes available, he says.

The data crunching and storage issues associated with the genetic

variants are not as daunting as they would appear, Masys says. Were

saved by the fact that you and I are actually 99% the same. And this is

just talking about genes. Theres another order of magnitude complex-

ity when you go out and measure proteins, because there are a lot more

of them than there are genes.

But the same principle applies: that if we have a data reference that

is our standard definition, then you and I just become a set of differ-

ences to the norm, and so it reduces the data storage problem by 99%.

Because at the front end what we can compute is, where there are no

differences, well just use the standard genome, and where there aredifferences, well store whats exactly and only you, and only me.

Storage is not the issue, but what systems wil l require is a robust,

actively used EMR with decision support. Vanderbilt has been develop-

ing its EMR for more than two decades and clinical decision support

tools since 1994, Masys says, yet fewer than 10% of hospitals nation-

wide have reached that level. So although many in the industry may

view the EMR as a process tool for preventing todays medical errors

and recordkeeping, its real use is as the basis for a higher level of deci-

sion support in personalized medicine.

What we do know is that the only way to deal with the complex-

ity of the patterns is with computerized decision support rules, says

Masys. Theres no way for a human being to look at these patterns and

be able to recognize them.

Targeting resistance

Nowhere is the science of personalized medicine more in practice than

in cancer care, where Vanderbilt researchers are tracking genetic vari-

ance in cancer tumors to more precisely target therapies. Certain lung

cancers have a sensitivity and resistance to targeted therapies such as

Iressa and Tarceva, which both work by blocking the activity of epider-

mal growth factor receptors.

A single mutation, however, may cause the tumors to become

resistant to the drug and allow tumors to return within a year, says

William Pao, MD, Ingram associate professor of cancer research at the

Vanderbilt-Ingram Cancer Center. Researchers found that by compar-

ing the genes of the tumors versus normal lung tissue, they identified a

strategy that a new combination of two drugserbitux and the com-

pound BIBW-2992can overcome tumors with the second mutation.

Paos research now is concentrating on getting standard genetic

mutation analysis done on cancer patients that will be built into the

universitys plans for decision support.

First we just wanted to get what we would consider standard

mutation analysis done in a prospective manner, meaning that the data

is done automatically on patients tumors, Pao says. And there were

testing for three main mutations in lung cancer and then one main

mutation in melanoma. Thats our one-year goal, and were already

there, basically. Our second goal is to develop an assay for detection of

more mutations. So we have one in lung, where we can detect about 40

mutations, and then one in melanoma, again about 40 mutations, all of

which are relevant to targeted therapy in cancer.

Dan Roden, MD,Assistant vice chancellorfor personalized medicine,Vanderbilt University

Medical Center



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ROUNDTABLE

e Promise of

MarkBoguski, MD

Department of Pathology,

Beth Israel Deaconess Medical

Center, Center for Informatics

at Harvard Medical School

RajuKucherlapati, PhD

Paul C. Cabot Professor

of Genetics, Harvard

Medical School

ClayMarsh, MD

Executive Director, Center

for Personalized Health

Care, The Ohio State

University Medical Center

GeraldMcDougall

Principal and U.S.

Health Sciences Leader,


DanRoden, MD

Assistant Vice Chancellor

for Personalized Medicine,

Vanderbilt University

Medical Center

Featuring highlights of a Roundtable of peer experts:

To see and hear the panelists introductions, click on their pictures above.

Having trouble viewing? Click here.





DANATHOMAS

Personalized Medicine

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ROUNDTABLE


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3434

HEALTHLEADERS MEDIA It seems that the definition of personal-

ized medicine varies. Could each of you define what it means to your

organizations?

CLAY MARSH, MD | The Ohio State University Medical Center | My

definition is system-based. I look at personalized healthcare as the abil-

ity to understand individual health and stratify outcomes based on their

genetics, and environment, including sleep, biological rhythm, exercise,

nutrition, and stress. The definition also includes the healthcare deliv-

ery system, data analysis, data integration and complexity, so that we

can automate executing evidence-based practices we know today and

the practices we learn tomorrow on a more personal, individual basis.

Standardizing care and reducing variability is an important opportunity.

MARK BOGUSKI, MD| Beth Israel Deaconess Medical Center

|Ill

expand on it in a little different direction. I feel that direct consumer

genetic testing is just really a subset of the larger challenge of educat-

ing patients enough to be comanagers of their health and wellness with

their physicians. In the personal genomics space, we have seen that the

The Promise of

PersonalizedMedicine

ROUNDTABLE

Jim MolpusStrategic Partnerships

Director

HealthLeaders Media

Philip BetbezeSenior Editor

Leadership

HealthLeaders Media

PPersonalized medicine is a phrase that encompasses all

that healthcare should bethat is, care carefully tailored

to the specific needs of the patient. Advances in the science

of genetics, along with the development of necessaryinfrastructure like the electronic medical record, may

finally be near to pushing personalized medicine from an

aspiration to the standard practice of care. HealthLeaders

Media recently convened a panel of experts from four of

the worlds leading medical centers to discuss how

personalized medicine is at work today, and what

healthcare leaders everywhere should expect in thenext few years to come.

DANATHOMAS

35


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ROUNDTABLE

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business community and direct consumers got

way ahead of the medical profession in provid-

ing these tools and technologies, and I dontthink that failure is an option to help the con-

sumers understand this information, wherever

it comes from. Patients have an important role,

too, because personalized medicine is preven-

tive medicine as well, and if people are informed

by health awareness and increased medical

knowledge, amplified by their personal genomic

information, I think they can be equipped to play

a much more active role.

GERALD MCDOUGALL | Pricewaterhouse-

Coopers| At PricewaterhouseCoopers, weve

defined it as a holistic, individual model of care

that examines each individuals unique makeup

and designs appropriate strategies for main-

taining wellness and treat-

ing illness. Others have

coined it P4 Medicine,

where its personalized,

preventive, predictive, and

participatory. I always

think those four Ps are

broad enough to capture a

lot of what were talking about, but each has its

own domains.

RAJU KUCHERLAPATI, PHD | Harvard

Medical School| To put it in the framework,

genetics as it relates to medicine has undergone

an evolution towards the end of last century,

and that evolution is the recognition that genet-

ics plays a very important role in virtually every

aspect of health and disease in the human popu-

lations, and were beginning to understand very

significantly what these genetic components

are that make us susceptible to disease, how we

respond to particular types of drugs, and how

we could enhance the wellness of human popula-

tions. So one of the evolutions that is happening

in the early stages of the century is our ability

to use this genetic and genomic information to

be able to make risk assessments for individuals

and say who is going to be susceptible to get

particular types of diseases, and to be able to

clinically diagnose, accurately diagnose a dis-

ease, and determine which drug is going to be

most effective for those individuals. So the abili-

ty to do all of these thingsthe ability to be able

to do risk assessment, to be able to do diagnosis,

to be able to do common prognosis, and to be

able to make the right treatment decisionsis

what I would call personalized medicine.

DAN RODEN, MD | Vanderbilt University Medical

Center| The ultimate in personalized medicine

will be when we understand what it is that

makes you an individual and tailor your health-

care to those factors. The things were working

on right now are obviously genes and genetic

variants. But the downstream effects of genes

and genetic variants are proteins and protein

variants, and so proteomics plays a role in that.

And proteomic profiling can be particularly use-

ful in some cancers. Thats not a future tense

Gerald McDougallPrincipal and U.S. Health

Sciences Leader


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vision. Thats upon us as we speak. Theres a lot

more than just genes and proteins that make us

who we are. Theres the way we were broughtup, the sociology in which we live, the society in

which we live, the family relations and the per-

sonal, professional relations that we have, all of

which color the way you approach healthcare,

whether youre a compliant person, a not-com-

pliant person, whether youre an obsessive per-

son or a not-obsessive person. Those things all

have to get taken into account when you start

to think about personalizing healthcare.

Current stateHEALTHLEADERS MEDIA Give us a status

report on personalized medicine as it relates to

getting into working clinical practice.

MARSH If you look at the Institute of

Medicines report, it takes about 17 years to

get a discovery from the bench to the bedside.

There have been some really nice examples of

where that time has been shortcutted, where

weve really benefited people. The HIV epidemic

is certainly one of those, where we aggressively

put drugs in clinic with activity against that

virus and changed HIV from a death sentence to

a chronic disease. In the pharmacogenomic field,

we now have more targeted therapies for peoplewith cancers based on the genetics of the tumor

to give treatment that is more precise, safer, and

more effective.

BOGUSKI Participatory medicine is a very

interesting phenomenon thats been going on for

several years with groups like e-Patients.net, and

these people are very assertive folks who not

only want to be participants in their healthcare

but actually the managers of it, because they

have a vested interest in getting the best treat-

ments. Thats not a model for the whole popula-

tion, because you have to have a lot of motiva-

tion and assertiveness to insist on that level of

participation. My message is that doctors have

to prepare themselves to anticipate this and not

reflexively react that, you know, Im the doctor

and you shut up, which is something Ive heard

in my training. I think the medical profession has

not yet fully realized that not only do they need

to update their training in terms of content, but

sort of rethink the way that theyre going to deal

with patients and consumers.

RODEN I trained as an internist, and then I

came to Vanderbilt in the late 1970s to study

something called clinical pharmacology. Andit took 10 years of my life to figure out how to

explain clinical pharmacology to those people

who are not in the discipline, like my mother.

Clinical pharmacology is the science of trying

to understand the mechanisms underlying vari-

ability in response to drugs in human beings and

using that information to use the drugs we have

now better or to develop new drugs. And theres

been a story in clinical pharmacology for the last30-plus years that there are genetic variants

that profoundly affect response to certain drugs.

And so the frustration has been, in the clinical

Clay Marsh, MDExecutive Director, Center

for Personalized Care

The Ohio State University

Medical Center

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pharmacology community, that we know that

there is variability in response to drugs, and we

know the mechanisms in some cases, and yet wedont act on those mechanisms. We dont incor-

porate those mechanisms into the way we prac-

tice medicine. One of the reasons is that genetic

testing has been difficult to accomplish and has

been sort of esoteric and foreign to most doc-

tors. So most doctors will say, Well, I accept the

idea that theres variability. Ill give the drugs,

and if my patient happens to be one of those out-

liers, then well figure that out and move on. Wecan do better.

KUCHERLAPATI The one practice where

personalized medicine is used extensively is in

pediatrics. There are many, many childhood

diseases for which the diagnosis, prognosis,

and treatment decisions will not be made in

the absence of genetic information. In cystic

fibrosis, for example, we are able to make a

determination that the child would have cystic

fibrosis, confirm it with a test, and then the

results that you obtain from the test would

determine how that child is going to be treated

and how you would be able to extend the lives of

those individuals . The second area that I think

has a significant impact is in cancer. The classic

examples of the use of genetic informationfor determining risk are in earlyonset breast

cancer, where its possible to do a test and be

able to determine whether the individuals have

mutations in BRCA1 or BRCA2 and to make

a risk assessment. Similar sorts of tests are

available for other types of cancers, such as

colon cancer. And then, following the prognosis

issues, there are actually treatment issues.

Maybe lung cancer is one of the best examples,where genetic testing of the tumor samples is

going to inform us as to what is the nature of the

drug that should be given to those individuals.

MCDOUGALL When were looking at the

opportunity to personalize medicine, we still

have to overlay it into a current healthcare sys-

tem that has a lot of variability. That variability,

in terms of the delivery of healthcare and then

clinical adoption, is a huge issue that needs to be

dealt with by the entire healthcare ecosystem.

Personalized medicine has been around for a

very long time. I dont know a physician who

wouldnt want the tools to get the right treat-

ment to the right patient at the right time. That

is not new for anyone looking across at a patient,

but I think the standardization of variability is

something that needs to be dealt with as well.

HEALTHLEADERS MEDIA Much of the

potential in personalized medicine is in the value

proposition it providesof avoiding unneces-

sary tests. That value may remain elusive for

now, but is the proposition changing?

MARSHIf you think about the cancer field or

the pediatrics field, there now are pressures

from the cost reimbursement side to test for

specific targets, so we use expensive therapies

specifically from a provider standpoint. So I

think that aligning the systems together to

Mark Boguski, MDDepartment of Pathology, Beth

Israel Deaconess Medical Center

Center for Biomedical Informatics

at Harvard Medical School

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create an automated framework to consistently

practice the same high-qu

pwc - impact of personalized medicine

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