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
[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
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