endometriosis phenotype development, validation, and ... · endometriosis •chronic disease in...
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![Page 1: Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in reproductive-age women •Endometrial cells grow outside uterus •Characterized through](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2c4cbc4f229d2cd64ddbb1/html5/thumbnails/1.jpg)
Endometriosis Phenotype Development, Validation, and Characterization from
Observational Health Databases
Mollie McKillop1, Sharon Lipsky Gorman1, Shadi Safar Goli1, Chris D’ambrosia1, Christoper Knoll2,
Patrick Ryan2, Noémie Elhadad1
1Columbia University; 2Janssen Pharmaceuticals
![Page 2: Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in reproductive-age women •Endometrial cells grow outside uterus •Characterized through](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2c4cbc4f229d2cd64ddbb1/html5/thumbnails/2.jpg)
Endometriosis Phenotype Development, Validation, and Characterization from
Observational Health Databases
Mollie McKillop1, Sharon Lipsky Gorman1, Shadi Safar Goli1, Chris D’ambrosia1, Christoper Knoll2,
Patrick Ryan2, Noémie Elhadad1
1Columbia University; 2Janssen Pharmaceuticals
![Page 3: Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in reproductive-age women •Endometrial cells grow outside uterus •Characterized through](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2c4cbc4f229d2cd64ddbb1/html5/thumbnails/3.jpg)
Endometriosis
• Chronic disease in reproductive-age women
• Endometrial cells grow outside uterus
• Characterized through surgical findings
• Menstrual pain and infertility as the most common characterization
• Prevalent
• Estimated to ~10% of women in reproductive age
• Highly enigmatic
• No known biomarker, etiology, or treatment response
• Long lag to diagnosis (~10 years)
OHDSI Call – Oct 30, 2018
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Research gaps
• Incomplete characterization • Systemic condition with symptoms beyond dysmenorrhea and infertility
• From onset of symptoms to after diagnosis
• Because misdiagnoses/under-diagnosis, need to identify the patterns of endo patients prior to diagnosis towards earlier/better detection
• Lack of validated phenotype• Epidemiological studies rely on single high-level ICD code
• Types of endometriosis have been proposed but focus on surgical findings and do not correlate with patient experience of disease
OHDSI Call – Oct 30, 2018
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Research questions
1. What is an accurate phenotype for endometriosis to identify cohorts from EHR and claims databases?
2. What are the patterns of patients experiences before diagnosis? • Signs/symptoms, treatments, healthcare utilization patterns, etc.
• Additional desiderata: • Phenotype valid across claims and EHR databases to identify a wide range of
patients
• Open access to other OHDSI members
OHDSI Call – Oct 30, 2018
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Methods
1. Define and validate an endometriosis phenotype for EHRs / claims
databases
2. Characterize cohorts pre-diagnosis across databases
OHDSI Call – Oct 30, 2018
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Relevant concepts
• Endo diagnosis: endometriosis diagnosis codes (including adenomyosis)
• Endo-related procedures: guideline-based procedures for endometriosis
diagnosis and treatment (e.g., pelvic laparoscopy)
• Endo-prevalent procedures: procedures present >50% of patients with
≥1 endo diagnosis
• Endo-related imaging procedures: guidelines-based imaging procedures
(e.g. pelvic MRI)
OHDSI Call – Oct 30, 2018
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Cohort definition experiments
OHDSI Call – Oct 30, 2018
Cohor
tInitial Event Inclusion Rules
A
endo-related procedures AND endo diagnosis
OR
endo-prevalent procedures AND endo diagnosis
Females ages 15-49
B
endo-related procedures AND endo diagnosis
OR
endo-prevalent procedures AND endo diagnosis
Females ages 15-49
AND
2 endo diagnosis
after index date
C
endo-related procedures AND endo diagnosis
AND
endo-related imaging procedures AND endo diagnosis before
index date
Females ages 15-49
D
endo-related procedures AND endo diagnosis
AND
endo-related imaging procedures AND endo diagnosis before
index date
Females ages 15-49
AND
2 endo diagnosis
after index date
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Cohort definition validation
• Manual chart review from clinical experts on EHR database (Columbia)• Index data between 1/1/2016 to 6/1/2018
• Reviewed records of patients across all cohort definitions
• Confirmed endometriosis diagnosis through histological analysis post-laparoscopy
• Gold-standard annotations of 1,406 patient records• Two annotators
• Kappa on 38 records: .89*• Determined N=38 provides expected confidence limits between .6 and 1
OHDSI Call – Oct 30, 2018
* p-value <.05
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Cohort definition validation
• Cohort B had highest precision/recall
• Negative predictive value 0.84
OHDSI Call – Oct 30, 2018
Cohort
name on
OHDSI.org
Precision Recall
Records in cohort
at Columbia EHR
2016-2018*
Total records in
cohort at Columbia
EHR 1999-2018
Cohort D 0.84 0.26 162 1,248
Cohort C 0.78 0.28 189 1,950
Cohort B 0.85 0.70 430 3,328
Cohort A 0.37 1** 1,406 5,666
* each of these cohorts was reviewed by clinical experts.
** all other cohorts are a subset of this cohort so recall=1.
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Cohort definitions
•Available at:
• http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769393
• http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769395
• http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769396
• http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769397
OHDSI Call – Oct 30, 2018
Best performing cohort we
used to characterize
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Methods
1. Define and validate an endometriosis phenotype for EHRs / claims
databases
2. Characterize cohorts pre-diagnosis across databases
OHDSI Call – Oct 30, 2018
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Cohort characterization
• Select best-performing cohort, Atlas characterization
• Analysis carried out on four databases
• Columbia EHR (Columbia EHR)
• Optum® Clinformatics® Extended DataMart (Optum)
• IBM MarketScan® Commercial Database (MCD)
• IBM MarketScan® Multi-State Medicaid Database (MMMD)
• Report on prevalent (>10% of patients) conditions and drugs
• For comparison, prevalence in general cohort of women of reproductive
age
OHDSI Call – Oct 30, 2018
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Cohort characterization
• Overall >480,000 patients in endometriosis cohort
OHDSI Call – Oct 30, 2018
Database Total records in cohort
Columbia EHR 3,328
Optum 24,725
MMMD 54,609
MCD 398,015
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Conditions
OHDSI Call – Oct 30, 2018
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Comparison (not control) Group Conditions
OHDSI Call – Oct 30, 2018
0
10
20
30
40
Ute
rine le
iom
yom
aP
ain
in p
elv
isC
yst of ova
ryA
bdom
inal p
ain
Fem
ale
genita
l org
an s
ympto
ms
Dys
menorr
hea
Urinary
tra
ct in
fect
ious
dis
ease
Exc
ess
ive a
nd fre
quent m
enst
ruatio
nH
eadach
eC
hest
pain
Nonin
flam
mato
ry d
isord
ers
of th
e o
vary
Ess
entia
l hyp
ertensi
on
Nonin
flam
mato
ry d
isord
er of th
e v
agin
aA
nxi
ety
dis
ord
er
Vagin
itis
and v
ulv
ova
gin
itis
Rig
ht lo
wer quadra
nt pain
Irre
gula
r periods
Cough
Dys
pnea
Low
back
pain
Const
ipatio
n
Conditions
Patie
nts
(%)
Columbia EHR
Endo Cohort
Comparison Group
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Drugs
OHDSI Call – Oct 30, 2018
0
20
40
60
Anili
des
Natu
ral o
piu
m a
lkalo
ids
Pro
pio
nic
aci
d d
eriva
tives
Sero
tonin
(5H
T3) anta
gonis
tsS
ofteners
, em
olli
ents
Opiu
m a
lkalo
ids
and d
eriva
tives
Pro
ton p
um
p in
hib
itors
Benzo
dia
zepin
e r
ela
ted d
rugs
Benzo
dia
zepin
e d
eriva
tives
Pro
puls
ives
Pro
gest
ogens
and e
stro
gens
Penic
illin
s w
ith e
xtended s
pect
rum
Opio
id a
nest
hetic
s
Oth
er
dru
gs
for
gast
roin
test
inal d
isord
ers
Macr
olid
es
First
-genera
tion c
ephalo
sporins
Conta
ct la
xativ
es
Flu
oro
quin
olo
nes
Vita
min
D a
nd a
nalo
gues
H2-r
ece
pto
r anta
gonis
ts
ATC Class 5
Patien
ts(%
)
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Comparison Group Drugs
OHDSI Call – Oct 30, 2018
0
20
40
60
Anili
des
Pro
pio
nic
aci
d d
eriva
tives
Natu
ral o
piu
m a
lkalo
ids
Softeners
, em
olli
ents
Opiu
m a
lkalo
ids
and d
eriva
tives
Sero
tonin
(5H
T3) anta
gonis
ts
Benzo
dia
zepin
e r
ela
ted d
rugs
Penic
illin
s w
ith e
xtended s
pect
rum
First
-genera
tion c
ephalo
sporins
Conta
ct la
xativ
es
Benzo
dia
zepin
e d
eriva
tives
Vita
min
D a
nd a
nalo
gues
Pro
ton p
um
p in
hib
itors
Pro
gest
ogens
Macr
olid
es
Pro
gest
ogens
and e
stro
gens
H2-r
ece
pto
r anta
gonis
tsP
ropuls
ives
Oth
er
pla
in v
itam
in p
repara
tions
Oth
er
dru
gs
for
gast
roin
test
inal d
isord
ers
Folic
aci
d a
nd d
eriva
tives
Solu
tions
for
pare
nte
ral n
utriti
on
Alu
min
ium
com
pounds
Asc
orb
ic a
cid (
vita
min
C), p
lain
Iron b
ivale
nt, o
ral p
repara
tions
Flu
oro
quin
olo
nes
Glu
coco
rtic
oid
s
ATC Class 5
Patien
ts(%
)
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Discussion
• First study to develop well-validated endometriosis phenotype for
cohort selection
• Findings across databases consistent with ongoing endometriosis research
• Primary symptoms present prior to diagnosis related to pelvic pain and heavy pain
medication
• Results congruent with new knowledge about endometriosis
• Beyond dysmenorrhea and pelvic pain, systemic impact of disease (i.e. anxiety,
constipation)
• OHDSI essential for characterization
• Wouldn’t have started to get full picture w/o collaborators!
OHDSI Call – Oct 30, 2018
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Next steps
• Characterize in larger, more diverse cohort
• Get in touch if you’d like to participate
• All definitions available on ohdsi.org and further queries available on demand
• Use phenotype definition for patient-level prediction
• In women in reproductive age presenting in ED with abdominal pain, who is likely
to be diagnosed with endometriosis 1year+ later?
• Using PLP modules
• Get in touch if you’d like to participate
OHDSI Call – Oct 30, 2018
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Thanks, questions?
• Columbia OHDSI bootcamp participants
OHDSI Call – Oct 30, 2018
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Comparison (not control) Group Conditions
0
20
40
60
Adult
health
exa
min
atio
nA
bdom
inal p
ain
Sin
gle
live
birth
Gyn
eco
logic
exa
min
atio
n
Patie
nt cu
rrently
pre
gnant
Neve
r sm
oke
d tobacc
oD
eliv
ery
norm
al
Headach
e
Urinary
tra
ct in
fect
ious
dis
ease
Fam
ily h
isto
ry o
f cl
inic
al f
indin
gC
hest
pain
Vagin
itis
and v
ulv
ova
gin
itis
His
tory
of cl
inic
al f
indin
g in
subje
ct
Fem
ale
genita
l org
an s
ympto
ms
Ess
entia
l hyp
ert
ensi
on
Scr
eenin
g for
malig
nant neopla
sm o
f bre
ast
Acu
te u
pper
resp
irato
ry in
fect
ion
Ante
nata
l ultr
aso
und s
can for poss
ible
abnorm
alit
yP
rim
igra
vida
Low
back
pain
Ante
nata
l scr
eenin
gP
ain
in li
mb
Acu
te p
hary
ngiti
sA
sthm
a
Com
plic
atio
n o
ccurr
ing d
uring p
regnancy
Cough
Subse
quent st
age o
f st
aged o
pera
tion
Pre
gnancy
test
negativ
eB
reast
lum
p
Conditions
Pa
tients
(%)
OHDSI Call – Oct 30, 2018