Professional Documents
Culture Documents
Healthcare Model
Clinical medicine
Care processes
System resources
Biological modeling
Clinical medicine
Care processes
System resources
• Object oriented
• Continuous
• Physiology based
• Very deep and very broad
• and it operates at the level of detail that
clinicians and administrators consider essential
for making decisions
Joe.
Joe Miner
OK Joe.
I hope you’re not
ticklish…
That’s good.
Nice belly, Joe.
Now we’re going to need to
do a sort of x-ray
OK.
The reason we’re
doing this is that we
want to show you that
every simulated
person in the model,
like Joe, has organs,
such as…
Heart
Pancreas
Circulatory
system
Fat cells
Gut Muscle
The organs and
their cells carry out
metabolic
functions,
such as…
GLYCOGEN
GLYCOGEN CIRCULATING
HEPATIC GLUCOSE
GLUCOSE
GLUCOSE
GLUCOSE
PRODUCTION
GLUCOSE
UPTAKE BY
MUSCLE
GLUCOSE SUGARS
UPTAKE
BY FAT
In the model, these
functions are regulated just
as they are in a real person.
For example, in response to
the circulating levels of
glucose, the pancreatic beta
cells will secrete insulin
GLYCOGEN CIRCULATING
HEPATIC GLUCOSE
GLUCOSE GLUCOSE INSULIN
PRODUCTION
GLUCOSE
UPTAKE BY
MUSCLE
GLUCOSE SUGARS
UPTAKE
BY FAT
And diseases can occur.
For example, in a person
with diabetes the effect of
insulin on uptake of
glucose by the muscle
and fat is decreased.
GLYCOGEN
HEPATIC
GLUCOSE GLUCOSE INSULIN
PRODUCTION
Diabetes
GLUCOSE
UPTAKE BY
MUSCLE
GLUCOSE SUGARS
UPTAKE
BY FAT
Diabetes
Diabetes also affects the
effect of insulin on
production of glucose by
the liver cells
GLYCOGEN
Diabetes
HEPATIC
GLUCOSE GLUCOSE INSULIN
PRODUCTION
GLUCOSE
UPTAKE BY
MUSCLE
GLUCOSE SUGARS
UPTAKE
BY FAT
If we were to illustrate the
biological variables and
relationships in the model
that affect the metabolism
of glucose, it would look
something like this
Unexplained
Family Insulin OGT OGTT test
Gliburide Insulin level variance in
history treatment
OGT
Random Random
Diabetes
plasma plasma
Sex diagnosis
glucose glucose test
Type 1 Insulin
Diabetes production
feature Joint (Pancreas) Glucose
Race/ uptake by Random FPG test
Diabetes
ethnicity muscle error and
Type 2 feature
Insulin variation
Diabetes efficiency FPG
feature (Muscle) Glucose HbA1c test
Age production
Insulin by liver
efficiency Untreated Care Urine
Age, sex, (Liver) insulin level processes ketone test
BMI race/ Normal liver To
ethnicity glucose treatment
production Fractional models
Keto-
Metformin change in
acidosis
Insulin
Height Weight
Diet and Hypo-
FPG
exercise glycemia
Patient
Diabetes takes action
Diabetes Propensity
blood HDL LDL Triglyceride Blurred
Smoking cardiac risk to blurred
pressure cholesterol cholesterol s vision
factor vision
factor
Memory
Mean Systolic Coronary
Peripheral Propensity
arterial blood artery Polyuria
resistance to polyuria
pressure pressure stenosis FPG
Perception
To the
To the To the To the Coronary
Propensity
Retinopathy Nephropath Neuropathy artery Thirst
to thirst
model y model model disease
model A KAISER PERMANENTE INNOVATION
All of that, and
many, many
more variables
that are important
to the
complications of
diabetes and to
other diseases, Family
history
Gliburide
Insulin
treatment
Insulin level
Unexplained
variance in
OGT
OGT
Random
OGTT test
Random
plasma
Diabetes
plasma
are being
Sex diagnosis
glucose glucose test
Type 1 Insulin
Diabetes production
feature Joint (Pancreas) Glucose
Race/ uptake by Random FPG test
Diabetes
ethnicity muscle error and
Type 2 feature
Insulin variation
Diabetes efficiency FPG
feature (Muscle) Glucose HbA1c test
Age
calculated
production
Insulin by liver
efficiency Untreated Care Urine
Age, sex, (Liver) insulin level processes ketone test
BMI race/ Normal liver To
ethnicity glucose treatment
production Fractional models
Keto-
Metformin change in
UKPDS acidosis
Insulin
continuously in
data
Height Weight
Diet and Hypo-
FPG
exercise glycemia
Patient
Diabetes takes action
Diabetes Propensity
blood HDL LDL Triglyceride Blurred
Smoking cardiac risk to blurred
pressure cholesterol cholesterol s vision
factor vision
factor
every simulated
Memory
Mean Systolic Coronary
Peripheral Propensity
arterial blood artery Polyuria
resistance to polyuria
pressure pressure stenosis FPG
Perception
person in the
To the
To the To the To the Coronary
Propensity
Retinopathy Nephropath Neuropathy artery Thirst
to thirst
model y model model disease
model
model
• Priority setting
• Strategic goals
• Research
• How “ideal” research trials translate to
“real” clinical settings
• Logistics, use of resources
• Costs, cost-effectiveness, and value
• Planning
A KAISER PERMANENTE INNOVATION
The idea is that we can use the virtual world to
learn the effects of lots of different types of
interventions that would be infeasible to study
through empirical methods (more research), for a
variety of reasons:
• Too high a cost
• Too long time needed for a new study
• Too many patients needed
• Unwillingness of patients and/or physicians to
participate
• Too large a number of options to study
• Technologies that are changing too rapidly
A KAISER PERMANENTE INNOVATION
This is very important, because
I mean, I know
that my
equations are
working fine. But
I’m not so certain
about the other
jokers who are in
here with me.
0.1
Fraction of patients
Placebo group
0.08
0.06
Treated group
0.04
0.02
0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Years
A KAISER PERMANENTE INNOVATION
The dotted lines showed what the
model calculated
Major Coronary Events in Heart Protection Study
0.14
Dotted lines are the model’s results
0.12
0.1
Fraction of patients
Placebo group
0.08
0.06
Treated group
0.04
0.02
0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Years
A KAISER PERMANENTE INNOVATION
Here’s another example, the Diabetes
Prevention Program
• Population: men and women over age 25.
broad range of racial and ethnic groups.
Prediabetes (IGT or IFG)
• Treatments: intensive lifestyle vs.
Metformin vs. standard care
• Size: 3000
• Mean duration: 2.8 years
A KAISER PERMANENTE INNOVATION
In this case, the results were calculated by
the model before the real results were
known. This is what the model predicted.
DPP: Diabetes Progression
0.5
0.45 Control
0.4 Metformin
0.35
Lifestyle
0.3
Fraction
0.25
0.2
0.15
0.1
0.05
0
0 1 2 3 4 5
Time (years)
0.45 Control
0.4
Metformin
0.35
Lifestyle
0.3
Fraction
0.25
0.2
0.15
0.1
0.05
0
0 1 2 3 4 5
Time (years)
0.2
0.15
Intensive
0.1 treatment
0.05
0
0 2 4 6 8 10 12 14
Time (years)
A KAISER PERMANENTE INNOVATION
This is what was calculated by the model
UKPDS: MI (fatal and non-fatal)
0.3
The dotted lines are the model’s results
0.25
Conventional
treatment
Fraction of patients
0.2
0.15
Intensive
0.1
treatment
0.05
0
0 2 4 6 8 10 12 14
Time (years)
A KAISER PERMANENTE INNOVATION
We have done this for 74 different combinations
of populations, treatments and outcomes. This
chart compares results calculated by the model
(y-axis) against results of the real trial (x-axis).
0.6
Each dot represents
an arm of a trial. The
Results calculated by model
0.5
0
0 0.1 0.2 0.3 0.4 0.5 0.6
Results from trials
A KAISER PERMANENTE INNOVATION
One would not expect perfect
correspondence because of random factors,
related to the number of people in the trial
• 71 of 74 are well within sampling error
• The other 3 have good explanations
– either it just missed (e.g. p = .04) (which is to
be expected statistically)
– or the description of the trial was incomplete
• 54 of 74 are within ± 1 standard deviation
• For all 74 exercises: r = 0.99
A KAISER PERMANENTE INNOVATION
For some of the trials, some of the data
from the trial were used to help build
parts of the model. The other trials are
100% independent
• For the exercises that were not used at all to
build the model (100% independent), the
correlation between the model and the trial was
still extremely high
• The correlation was still r = 0.99
• Liver • Muscle
• Pancreas • Fat
• Heart • Kidneys
• Vascular • Eyes
• Nerves • Lungs
• Gut
Biological modeling
Clinical medicine
System resources
Unexplained
Family Insulin OGT OGTT test
Gliburide Insulin level variance in
history treatment
OGT
Random Random
Diabetes
plasma plasma
Sex diagnosis
glucose glucose test
Type 1 Insulin
Diabetes production
feature Joint (Pancreas) Glucose
Race/ uptake by Random FPG test
Diabetes
ethnicity muscle error and
Type 2 feature
Insulin variation
Diabetes efficiency FPG
feature (Muscle) Glucose HbA1c test
Age production
Insulin by liver
efficiency Untreated Care Urine
Age, sex, (Liver) insulin level processes ketone test
BMI race/ Normal liver To
ethnicity glucose treatment
production Fractional models
Keto-
Metformin change in
UKPDS acidosis
Insulin
data
Height Weight
Diet and Hypo-
FPG
exercise glycemia
Patient
Diabetes takes action
Diabetes Propensity
blood HDL LDL Triglyceride Blurred
Smoking cardiac risk to blurred
pressure cholesterol cholesterol s vision
factor vision
factor
Memory
Mean Systolic Coronary
Peripheral Propensity
arterial blood artery Polyuria
resistance to polyuria
pressure pressure stenosis FPG
Perception
To the
To the To the To the Coronary
Propensity
Retinopathy Nephropath Neuropathy artery Thirst
to thirst
model y model model disease
model