Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in...

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

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

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


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


Methods

1. Define and validate an endometriosis phenotype for EHRs / claims

databases

2. Characterize cohorts pre-diagnosis across databases


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)


Cohort definition experiments


Cohor

tInitial Event Inclusion Rules

A

endo-related procedures AND endo diagnosis

OR

endo-prevalent procedures AND endo diagnosis

Females ages 15-49

B


OR

endo-prevalent procedures AND endo diagnosis

Females ages 15-49

AND

2 endo diagnosis

after index date

C


AND

endo-related imaging procedures AND endo diagnosis before

index date

Females ages 15-49

D


AND

endo-related imaging procedures AND endo diagnosis before

index date

Females ages 15-49

AND

2 endo diagnosis

after index date

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


* p-value <.05

Cohort definition validation

• Cohort B had highest precision/recall

• Negative predictive value 0.84


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.

Cohort definitions

•Available at:

• http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769393





Best performing cohort we

used to characterize

http://www.ohdsi.org/web/atlas/#/cohortdefinition/1769393




Methods

1. Define and validate an endometriosis phenotype for EHRs / claims

databases

2. Characterize cohorts pre-diagnosis across databases


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


Cohort characterization

• Overall >480,000 patients in endometriosis cohort


Database Total records in cohort

Columbia EHR 3,328

Optum 24,725

MMMD 54,609

MCD 398,015

Conditions


Comparison (not control) Group Conditions


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

Drugs


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(%

)

Comparison Group Drugs


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(%

)

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!


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


Thanks, questions?

• Columbia OHDSI bootcamp participants


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

(%)


Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in...

Documents

Transcript of Endometriosis Phenotype Development, Validation, and ... · Endometriosis •Chronic disease in...