A person with Type 1 diabetes must take insulin every day just to stay alive. Type 2 diabetes is far more common. prevalence of diabetes increases with …
What Good is Personalized Medicine if ?
By Stan N Finkelstein, Anthony J Sinskey, and Scott M Cooper
As weve discussed in earlier columns, the promise of personalized
medicine held out by greater understanding of the genetics of disease is
perhaps the greatest impetus for research in this area To understand the
genome is to understand the drugs to which patients will respond and that
they can take safely The future will be one where there isnt just the
disease, but a family of that disease about which we know more and more
- and about which we can do more and more
Diabetes is a case in point Today we talk of Type 1 and Type 2 diabetes
Type 1 diabetes is an autoimmune disease; such diseases result when the
bodys immune system - its system for fighting infection - turns against a
part of the body In diabetics, the immune system attacks and destroys the
insulin-producing beta cells in the pancreas, and then the pancreas
produces little or no insulin A person with Type 1 diabetes must take
insulin every day just to stay alive
We find Type 1 diabetes developing most often in children and young adults
However, the disease can appear at any age The symptoms of Type 1
diabetes
usually develop rather quickly, although the destruction of the beta cells
may have begun many years earlier
Scientists believe a combination of genetic and environmental factors cause
the bodys immune system to wage this war against the pancreas Viruses may
also be involved
Type 2 diabetes is far more common It tends to develop in adults over 40,
and is most common in people over age 55 The Type 2 diabetic is typically
overweight, and because of the obesity problem for children and adolescents
in the United States, this type of the disease is becoming more common
among young people The symptoms develop gradually, with an onset much less
sudden than with Type 1 Some people exhibit no symptoms
Type 2 diabetes differs from Type 1 in that the pancreas is usually
producing sufficient insulin, but the body cant seem to use it
effectively Researchers have yet to determine the reasons for this insulin
resistance Eventually, insulin production does decrease, and then the
result is the same as for Type 1 diabetes - glucose builds up in the blood
and the body cannot make efficient use of that blood
Despite that diabetes is always categorized as Type 1, Type 2, or
gestational a
problem faced by about 4 percent of all pregnant women and
which usually disappears after birth, genomics research suggests that
there are probably millions of types, or at least sub-types, affecting
patients in millions of minutely different ways
If genomic research into diabetes can hone in on the differences, drug
developers can make medicines that attack the individual patients disease
characteristics - hence, personalized medicine The good health that can
result from drug treatment will be better, and more widespread, and thus of
greater benefit to society This is particularly true in the case of a
disease like diabetes, which has such devastating health and economic
consequences
The diabetes epidemic
To get an idea of just how bad the diabetes epidemic really is, consider
that diabetes is the fifth-leading cause of death by disease in the United
States The prevalence of diabetes increases with age And because
diabetics are at higher risk for heart and blood vessel disease, kidney
failure, strokes, blindness, amputation, nerve damage, and a host of other
chronic conditions, the disease makes a significant contribution to overall
higher rates of morbidity
To call it an
epidemic is far from hyperbole A survey by the Centers for
Disease Control showed that from 1990 to 1998, the prevalence of diabetes
in the United States increased 76 percent among people age 30 to 39 Today,
6 percent of the US population has some form of diabetes Some 10 percent
have the Type 1 form of the disease
One could speculate that if cause of death by disease were tracked like
the top 40 hits on the Billboard chart, diabetes would actually be fifth
with a bullet Why? The prevalence of the disease also is higher among
certain ethnic and racial minorities The US population is becoming
increasingly diverse both racially and ethnically This, argues the
American Diabetes Association, portends a substantial increase in the size
of the population with diabetes If diabetes prevalence rates remained
constant over time, controlling for age, sex, race, and ethnicity, then
based on Census Bureau population projections, the number of people
diagnosed with diabetes could increase to 145 million by 2010 and to 174
million by 2020[i]
According to the World Health Organization, the scale of the problem that
diabetes poses to world health is still widely under recognized At least
177
million people worldwide suffer from diabetes [in 2000]; this figure is
likely to more than double by 2030[ii]
To round out the picture of just how serious the burden of diabetes really
is, mull over some economic figures for the United States According to the
American Diabetes Association, the figures for diabetes-related
expenditures in 2002 were staggering Direct medical expenditures alone
totaled 918 billion and comprised 232 billion for diabetes care, 246
billion for chronic complications attributable to diabetes, and 441
billion for excess prevalence of general medical conditions Inpatient days
439, nursing home care 151, and office visits 109 constituted
the major expenditure groups by service settings
The ADA study also looked at indirect medical costs Attributable indirect
expenditures resulting from lost workdays, restricted activity days,
mortality, and permanent disability due to diabetes totaled 398 billion
Finally, according to the ADA, people with diabetes had medical
expenditures that were 24 times higher than expenditures that would be
incurred by the same group in the absence of diabetes[iii]
Quite obviously, the cost of diabetic care is enormous The
comorbidities
and complications mentioned earlier drive these high costs On top of this,
a huge percentage of diabetes patients dont even receive the care
recommended by the World Health Organization, Centers for Disease Control,
and the ADA And a good half of diabetics do not carry out their
recommended self-care
What does all this have to do with personalized medicine? We may well get
to better drugs for diabetics thanks to genomics These drugs may well be
personalized for the individual patients disease characteristics But we
still have to get people to take their drugs and follow their disease
management programs
Combining technologies
All too often, research focuses on the technical side of a question to
what seems like the total exclusion of the people side Personalized
medicine is a case in point So many researchers look at creating
individualized drugs, but who is thinking about making sure the drugs are
taken?
We think theres a very promising opportunity to combine drug technology
and behavioral science to ensure compliance with disease management
programs and thus realize the fullest potential for patients and society
After all, the greater the compliance, the
greater the benefits from
customized drug treatment
At a recent workshop sponsored by the Program on the Pharmaceutical Program
at the Massachusetts Institute of Technology, we learned of some
researchers who are looking at the behavioral end of the diabetes question,
and we began to think about the possibilities for combining self-care and
the future therapies promised by personalized medicine
InterMed Advisors, Inc showed us their solution to the problem of how to
capture the information necessary for clinicians to monitor effectively
diabetes patients who are involved in self-care programs, and how to get
feedback to patients every day to help them comply with their prescribed
treatment plans As InterMed put it, the solution aims at simplifying the
transmission of more frequent self-monitoring data; provides the most
useful data to clinicians; and encourages patients to take care of
themselves in a dynamic, informative, and engaging way
This kind of closed-loop feedback system could go a very long way in the
future world of personalized drugs, because it may well be a key component
of whatever formula is needed to solve the compliance problem
The system involves automatic
transmission of patient self-monitoring data
via the use of a wireless computer system The system analyzes the data
each day, at the personalized level of the individual patient, using time-
series analysis and other advanced mathematical techniques Communications
technology delivers customized feedback from physicians and nurse to
patients in their homes, through their televisions
The system looks promising and suggests InterMed may be right when it
claims it would decrease disease complications, emergency room visits,
hospital days, and total costs of care Thats good news, given the
billions of dollars at stake - as all the figures we provided earlier
indicate
Getting the person in personalized medicine to comply
It looks to us as if this combination of technologies - the drug
development technologies being researched by scientists working on genomics
and the computer technologies being utilized by folks like those at
InterMed - affords a really good beginning to the problem of compliance We
can imagine how it might be beneficial in the hypothetical future of
personalized medicine
For diabetes, we can posit that in the future clinicians will be able to
identify any number of
types of the disease based on an individual
patients characteristics One patient will have her type of diabetes
that is relatively easy to control, while another will have his type that
is very difficult to control - both within the broad context of, say, the
Type 1 diabetes as we define it today For the latter patient, intervention
assumes a greater criticality More diligence is needed But maybe our
patient is no more willing to comply with his treatment plan than seems to
be the case typically for patients
The existence of a closed-loop feedback system could be a major prompt for
positive action And the benefits are not limited to diabetics
Lets take atrial fibrillation AF, which is the most common form of
arrhythmia It affects about 2 million people in the United States each
year And its quite serious Although only a few years ago most healthcare
providers thought it was nuisance arrhythmia with few consequences,
recent research has uncovered complications directly related to AF that are
quite devastating These include congestive heart failure, stroke, and
cardiomyopathy
We dont know the definitive cause of AF, but researchers do know that
during atrial fibrillation there is
a high risk of blood clot formation,
which can lead to stroke Anticoagulation with warfarin has been shown to
be effective in reducing the risk of blood clot The dosage of
anticoagulants prescribed is tied to various laboratory tests
Just as with diabetes, the future of personalized medicine will likely
reveal widely variant, individualized risk profiles Some patients will be
controlled relatively easily with the kinds of anticoagulants available
today, while others may need personalized drugs Our increased knowledge of
the disease would also tell us details - unknown today - about the
difficulty of compliance
Combining the technologies, we think, is a way to propel forward the
promise of personalized medicine Whether its the kind of closed-feedback
loop system created by InterMed, something else we dont yet know about, or
a glimmer in some researchers eye on which she is just beginning to work,
we are convinced that this question needs to be answered: What good is
personalized medicine if people dont take their personalized drugs?
Notes
———————–
[i] American Diabetes Association, Economic Costs of Diabetes in the US
2002, Diabetes Care 26:3 March 2003 The
article cites US Bureau of
the Census: Population Projections Available from http://wwwcensus
gov/population/www/projections/popprojhtml Accessed October 2002
[ii] At the WHOs Diabetes Action Now webpage,
http://wwwwhoint/ncd/dia/ Accessed December 2003
[iii] American Diabetes Association, ibid
