elmer bernstam - personalized medicine

8/7/2019 Elmer Bernstam - Personalized Medicine

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Personalized Medicine Requires

Personalized Clinical Decision

Support

Elmer V. Bernstam, MD, MSE

Our view of a car

Ferrari Enzo 400 produced

6.0 L V12 putting out651 hp

12 mpg city18 mpg hwy

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Roads view of a car

0-60 mph in 3.14

sec

0-100 mph in 6.6

sec

Top speed 222 mph

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Our view vs. Roads view

The roads view is what determinesperformance

Similarly

The effects of personalized medicine (genomics)on health depend on what the clinician can do

Not on what the scientist can do

(Selected) Information challenges topersonalized medicine from the clinicalperspective

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From clinical perspective

Personalized medicine not new

We always individualized therapy using

Patient preferences

Non-genomic risk profile

Smoking, exposure to asbestos

Available facilities and resources

Co-morbidities: many patients have more thanone problem

Burke W, Psaty BM. Personalized Medicine in the era of genomics. JAMA. 2007;298(14):

1682-4.7

Mulrow C, Cook D, et al. (1997) Systematic reviews: critical links in the great chain of evidence. Annals of Internal

Medicine, 126: 389-91.8


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Whats new? quantitative difference

The amount of evidence exploding How much you have to know that you dont learn in

the encounter and is not common knowledge

Personalized medicine = dividing the populationinto smaller groups Non-genomic medicine: divide population into few

categories (2-4) with many members based on clinicalcharacteristics (e.g., age groups, gender, exposures,histology) then individualize based on what youlearn in the encounter (e.g., patient preferences)

Genomic medicine: divide population into manycategories with very few (1) members

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Many categories, few members

Nature (2000)

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Subdividing diseases

Diffuse Large B Cell Lymphomamultiple

diseases

Survival correlates with gene expression

Genomic medicine Biomedical

Scientist

This is cool!

We study diseases now we understand them

better

Getting at the fundamentals, rather than epi-

phenomena

Lets do more of this if we only had morefunding

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Genomic medicine -- Clinician

Personalized medicine is what weve been doing all along Genomics is just one more variable

Difference is quantitative not qualitative

We couldnt manage the information before How are we supposed to manage more of it?

I dont have the time to look it up in a book Thats out of date by the time its published anyway

As an aside: Policy Privacy Discrimination

How will insurance work without (or with greatly reduced)uncertainty?

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Genomic medicine -- Informatician

Its an opportunity

Genomic data tends to be discrete and well-defined Easier to represent in a computer compared to

traditional clinical data

How do we Still need to represent traditional clinical data thats

hard

Provide data within encounters, but not dominate theencounter?

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Incidentalome

False positives

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The problem

If you do enough tests you get false

positives

Gene chips can do 500,000 tests

No test has 100% sensitivity/specificity

Suppose that you had a VERY good test

100% sensitivity

0.01% false positive rate (i.e., specificity of 99.9%)

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Solution

Increase the prevalence

Only test a population that is at high risk of

disease

However, need to determine a pre-test

probability

What is the pre-test probability of a 45 year old

female with no affected 1st degree relatives, no

smoking history and two affected 2nd degree

relatives having pancreatic cancer?

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Humans bad at bedside math

At the bedside, not practical to

Retrieve relevant information

Crunch the Bayes theorem calculation

Prevalence

Probability of finding

Probability of disease given finding

Need decision support

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Suppose that your test was entirely

accurate

Positive predictor test increasesprobability by 10-40%1

May have multiple predictors

Suppose you have 20 predictors for pancreaticcancer

Still need to do bedside math based on toomuch data

1. Feero WR, Guttmacher AE, Collins FS. The genome gets personal almost. JAMA (2008) 299:11, p. 1351-2.

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Incidentalome -- Biomedical scientist

Some might say Is this my problem?

If it is

Need more precise data

Account for more variables

More precise predictions

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Incidentalome -- Clinician

Bad test I wont use it.

Too many false positives, too little useful

information

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Incidentalome -- Informatician

Computers ARE good at math

Trouble is, garbage in garbage out Results are only as good as the inputs

Cant rely on clinician to enter the data during 10 minuteencounter

Must determine prevalence in specific populationsmake them available during the encounter Drawing on real time data

National Regional Institutional my patients Thats hard need to represent clinical data, not just

genetic data Outcomes, demographics, treatments,

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