Kuan-Po Peng MD Kuan-Po Peng MD Adjunct Lecturer

National Yang-Ming University, Taiwan Taipei Veterans General Hospital, Taiwan

Disclosure

• Nothing to declareg

Experience from the Taiwan National H lth I R h D t bHealth Insurance Research Database

Today’s Overview

• Secondary data analysis on migraine-claims database-study design and statistical model-limitation and pitfalls

• Validation of diagnosis• Drug persistence, economic cost, or

adverse eventsadverse events

Taiwan National Health Insurance Research Database (NHIRD)Research Database (NHIRD)

Comprehensive reimbursement

Secondary data analysis

Strength WeaknessStrength WeaknessLarge number Population-

basedDiagnosis code ≠ Diagnosis

based

Extensive coverage gprescription, hospitalization, comorbidities.

ReimbursementPurpose

Coding error(inaccuracy)

i.e. NHIRD migraine cohort (n=759,027)

p ( y)

Clinical observation

3 migraine patients Hypothesis Migraine patients

developed yp

linked to Bell’s palsy?Bell’s palsy Bell s palsy?

Why use claims database?

LargeLarge l

Disease with low incidencesample

size

Statistical model I: cohort studyA i ti St d

Migraine cohort

Association Study

Follow-up

Comparison cohort(i.e. non-headache)

Outcome incidence comparison

Follow-up

p

Migraine and Bell’s palsy

Case Selection Comparison Selection

Case ExclusionComparison ExclusionExclusion

Case - Comparison Matching

Peng et al. Neurology 2015; 84: 116-24

Key issue:Validation of diagnosisValidation of diagnosis

Validation study Sensitivity analysisValidation studyNeurologist diagnosed migraine 91.6% accurate

Sensitivity analysisBell’s palsy aOR P-value

all 1 91 <0 001gusing ICHD-2

Ch t i

-all 1.91 <0.001-without pregnancy 1.91 <0.001-dx by neurologist 1.78 <0.001

Wang et al. J Formos MedAssoc. 2008;107:485–94.

Chart reviewy g

-steroid prescribed 1.53 <0.001-all of the above 1.59 <0.001

Yang et al. Ophthalmology. 2016 Jan;123(1):191–7.

Peng et al. Neurology 2015; 84: 116-24

Validation: alternative strategy

Improve coding Combine coding with p gaccuracy• Consecutive coding:

prescription / procedure• Pulmonary embolism +

e.g. ≥3 migraine diagnosis codeC d d b

anticoagulant prescription

• Codes made by specialist

• Myocardial infarction + cardiac catheterization

Key issues in cohort study

Comparison Statistical PossibleComparison cohort

Statistical model

Possible pitfalls

Matched on• Sex• Age

e.g. Cox Regression

• Unaccounted covariates

• Age • Propensity

score

ganalysis, with correction

• Medical surveillance

• …... bias

Uncorrected comorbidities

https://commons.wikimedia.org/wiki/File:Migraine_Comorbidities.PNG

Unaccounted covariates

Surveillance bias

SES

DIA

GN

OS

mbe

r of D

Num

Number of CLINICAL VISITS

Overcome surveillance biasP it S M t hiPropensity Score Matching

Age, Sex Social demographic, behavior

Migraine Control Comorbidities Adapted from http://www.summitllc.us/propensity-score-matching

What have we found?What have we found?

Migraine is associated CN disordersO hth l l i T i i l l i SSNHL

HR: 2.67 HR: 4.23 HR: 3.37 HR: 6.72

Ophthalmoplegia Trigeminal neuralgia SSNHL

HR: 1.8

BPPV

Y t l O hth l l 2016 123 191 7

HR: 2.03

Yang et al. Ophthalmology. 2016;123:191–7.Torpy et al. JAMA. 2013; 309:1058Lin et al. Cephalalgia. 2015 Dec 20. (advanced online) Chu et al. J Headache Pain. 2015; 16: 62.Chu et al. Cephalalgia. 2012;33(2):80–6.

Migraine and ischemic stroke

Peng et al. Cephalalgia 2016, Epub ahead of print

Migraine and venous thromboembolism

Accepted in Headache

Statistical model 2: Nested case control studyNested case-control study

ExposedExposed

Non‐exposed

Migraine patients without stroke

Non exposed

Exposure Comparison

Migraine patients

Exposed

Migraine patients with strokeNon‐exposed

Triptan use and ischemic stroke

Unpublished data

Nested-case control approach

Strength and statistical model selectionmodel selection

Sh t t E S i i lShort-term exposure on outcome

Exposure over different time interval

Statistical correction of covariatesoutcome

(e.g. drug)interval covariates

Implication from our studies

Associated with all migraine

Migraine with aura-specific associationsall migraine spec c assoc at o s

• Cranial neuropathy • Ischemic strokerelated: CN3,4,6, CN5, CN7, CN8D i

• Venous thromboembolism

MA specifically • Depression (not listed)

• Renal calculi (not listed)

p ylinked to vascular comorbidities?

Why vascular disease and MA ?

Central Hypertension

Vascular Comorbidity

Vascular ResistanceHypertension

(Schillaci, 2010)Comorbidity(Scher, 2005)

Resistance(Schillaci, 2010 )

Poorer Patent ProthromboticPoorer cholesterol profile

Patent foremen ovale(Carod-Artal, 2006)

Prothromboticstate (Hering-Hanit, 2001)profile

(Scher, 2005)

Drug related studies

Drug adherence(Triptan)

PPI and headache(Triptan)

• Better when prescribed by • Esomeprazole and neurologist

• Worse at local medical li i

lansoprazole increased the risk of headache

clinic

Chen et al. J Headache Pain. 2014;15:48. Liang et al. Cephalalgia. 2015;35:203-10

SummarySummary

TED speaker / data analyst Kenneth CukierKenneth Cukier

Big data is better data

BUT

JUNK IN JUNK OUTJUNK IN JUNK OUT

Methodology mattersMethodology matters

Acknowledgement:• My mentor: Prof. Shuu-Jiun Wang• My fellow neurologist / photographer:• My fellow neurologist / photographer:

Vincen Chuang, for all the Taiwan photos