Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Data‐driven Medicine in the Age of Electronic Health Records

Nigam Shah, MBBS, PhD

nigam@stanford.edu

[Big] Data in Medicine

ig Next gen‐seq,

?

Data Size

Bi

l

Next gen seq, iPOP ?

Smal

Small Large

Number of samples

Claims, EMR, Clinical notes

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Practice‐based evidenceTerms, Concepts Variables

Counts

Associations of interest

Recognizing events

1T‐1 T‐2 .. .. .. .. .. .. .. .. .. T‐i

P‐1 1 0 ‐1

P‐2

:

:

:

:

1.8 

million

Sens 73%

Event / Outcome concepts

Peripheral artery disease

Peripheral vascular disease

:

Intermittent claudication2

:

P‐n

~ 3 millionDefer binding 

pDefer binding to concepts

Sens 73%Spec 96%PPV 83%F1 78%

Claudication (finding)

Count positive, present mentions• Keeping track of negation• Keeping track of history, family history 

2

3

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Patient‐feature matrix• rows = patients• columns = medical concepts

107 textual notes

C1 … … Cn

C1 1 0.6 0.5 0.6

: 1 0.2 0.3

: 1 0.1

Cn 1

P1 … … Pn

P1 1 0.1 0.7 0.8

: 1 0.5 0.8

: 1 0.4

Pn 1

doppler studies

ultrasound imaging

amoxicillin

cephalexin

angioplasty

doppler ultrasonography

cane

h h h dand conditions?

Who has these drugs and conditions? p

What is special about these patients?

zolpidem

pravastatin

nifedipine

congestive heart failure

insulin glargine

cilostazol

transplantation

trimethoprim

bypass

surgical revision

atherectomy

bypass graftvascular surgical

procedures

testosterone

fentanyl

heart failure

coronary angiography

pantoprazole

hydralazine

amiodarone

obesity

wheelchair

diazepam

pneumonia

tacrolimus

sulfamethoxazole

temazepam

decompressive incision

fluoroscopic angiography heart

transplantation

revascularization

diagnostic imaging

vascular diseases

ramipril

angioplasty

carotid endarterectomy

Turning text into safety signalsText clinical note

x 107

Can detect 6 out of 9 recalls in the past decade

Patient‐feature matrix• rows = patients• columns = medical concepts

MI No MI

Vioxx a  b 

No Vioxx c  d 

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Gold Standard set:

Performance

• 28 positive test cases• 165 negative test cases• 12 events• 78 drugs

1.01.0

1.01.0

AERS: AUC 0.72 – 0.83*Notes: AUC 0.75 – 0.80* Harpaz et al. Performance of Pharmacovigilance Signal Detection Algorithms for the FDA Adverse Event Reporting SystemNature ‐ Clinical Pharmacology & Therapeutics 2013

.52.

02.

53.

0

1.9

015

20lansoprazole − mi

95%

CI)

(thou

sand

s)

?

New discovery or false positive?Text clinical note

x 107

2000 2002 2004 2006 2008 2010

0.0

0.5

1.0

1

05

10

Year

OR

(9

Exp

osur

e (

A BPatient‐feature matrix• rows = patients• columns = medical concepts

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Primary Cohort  Outcome of interest Patient factors associated with uveitis

Juvenile Idiopathic Arthritis and Uveitis

(Juvenile Idiopathic Arthritis)ICD 9 codes

696.0, 714.0, 714.2, 714.3, 714.9, 720.2, 720.9

Terms:

Juvenile idiopathic arthritis, JIAJuvenile rheumatoid arthritis, JRA

(Chronic Uveitis)ICD 9 codes

364.00 (acute)364.10 (chronic)

Terms:

UveitisIridocyclitis

ANA positive, positive ANApsoriasisallergic, allergyoligoarticular, oligo‐onset,pauciarticular, pauci‐onset,monoarthritis, monoarticularrheumatoid factor positive,rf positive, positive rheumatoid factor, positive rf

Examples of allergy medications in clinical records:

Nasal steroids: Flonase, NasacortOral Antihistamines: Allegra, Zyrtec,Juvenile rheumatoid arthritis, JRA

Psoriatic arthritisJuvenile spondyloarthropathy,spondyloarthritis,enthesitis related arthritis,sacroiliitis,reactive arthritis

IridocyclitisIritis

Oral Antihistamines: Allegra, yrtec,Claritin, Clarinex, Benadryl, XyzalNasal antihistamines: AstelinLeukotriene inhibitors: SingulairDecongestant: Sudafed

Associations to test• Known positive association with 

• oligoarticular onset of JIA

• positive ANA status

• possible positive association with psoriasis

• Known negative association with

• RF status

• If we can confirm these, then the EMR data can be used to test a new one.

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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Cluster analysis of residual features

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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JIA JIA + uveitis

Difference

Text clinical notes

x 107

Pediatrics 2040 Conference – 10/5/2013 10:50 AM – Nigam Shah, MBBS, PhD

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AcknowledgementsCurrent: Paea LePendu, Rave Harpaz, Ken Jung, Tyler Cole, Greg Gaskin, Will Chen, Alison Visher

Alums: Anna Bauer‐Mehren, Srini Iyer, Amogh Vasekar, Sandy Huang, 

Collaborators: John Cooke Yohannes Ghebremariam Nick LeeperCollaborators: John Cooke, Yohannes Ghebremariam, Nick Leeper, Jennifer Frankovich, Tina Hernandez‐Boussard, Suzann Pershing

Funding:NLM – R01 LM011369 (PI, Nigam Shah)NIGMS – R01 GM101430 (PI, Nigam Shah)NHGRI – U54 HG004028 (PI, Mark Musen)NLM – U54 LM008748 (PI, Zak Kohane)NINDS – R01 NS080145 (PI, Vance Lemmon)

Seed funds: Dept. of Medicine, TRAM, Population Health Sciencesp pFellowships: Med Scholars, Siebel Scholars Foundation, Stanford Graduate Fellowship

STRIDE Team membersTodd Ferris, Tanya Podchiyska

Alex Skrenchuk, BMIR‐IT