Adjunct Lecturer. National Yang-Ming University, Taiwan. Taipei Veterans General Hospital, Taiwan

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2 Kuan-Po Peng MD Adjunct Lecturer National Yang-Ming University, Taiwan Taipei Veterans General Hospital, Taiwan

3 Nothing to declare Disclosure

4 Experience from the Taiwan National Health Insurance Research Database

5 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 events

6 Taiwan National Health Insurance Research Database (NHIRD) Comprehensive reimbursement

7 Secondary data analysis Strength Large number Population- based Weakness Diagnosis code Diagnosis i.e. NHIRD migraine cohort (n=759,027) Extensive coverage prescription, hospitalization, comorbidities. Reimbursement Coding error Purpose (inaccuracy)

8 Clinical observation 3 migraine Hypothesis Migraine patients linked to developed Bell s palsy? Bell s palsy

9 Why use claims database? Large sample Disease with low incidence size

10 Statistical model I: cohort study Migraine cohort Association Study Follow-up Comparison cohort (i.e. non-headache) Outcome incidence comparison Follow-up

11 Migraine and Bell s palsy Case Selection Comparison Selection Case Exclusion Comparison Exclusion Case - Comparison Matching Peng et al. Neurology 2015; 84:

12 Key issue: Validation of diagnosis Validation study Neurologist diagnosed migraine 91.6% accurate using ICHD-2 Chart review Wang et al. J Formos Med Assoc. 2008;107: Yang et al. Ophthalmology Jan;123(1): Sensitivity analysis Bell s palsy aor P-value -all < without pregnancy 1.91 < dx by neurologist 1.78 < steroid prescribed 1.53 < all of the above 1.59 <0.001 Peng et al. Neurology 2015; 84:

13 Validation: alternative strategy Improve coding accuracy Consecutive coding: e.g. 3 migraine diagnosis code Codes made by specialist Combine coding with prescription / procedure Pulmonary embolism + anticoagulant prescription Myocardial infarction + cardiac catheterization

14 Key issues in cohort study Comparison Statistical Possible cohort model pitfalls Matched on e.g. Sex Cox Regression Age Propensity analysis, with score correction... bias Unaccounted covariates Medical surveillance

15 Uncorrected comorbidities

16 Unaccounted covariates

17 Surveillance bias Number of DIAGNOS SES Number of CLINICAL VISITS

18 Overcome surveillance bias Propensity Score Matching Age, Sex Social demographic, behavior Migraine Control Comorbidities Adapted from

19 What have we found?

20 Migraine is associated CN disorders Ophthalmoplegia Ti Trigeminal i neuralgia SSNHL HR: 2.67 HR: 4.23 HR: 3.37 HR: 6.72 HR: 1.8 HR: 2.03 BPPV Yang et al. Ophthalmology. l 2016;123: Torpy et al. JAMA. 2013; 309:1058 Lin et al. Cephalalgia Dec 20. (advanced online) Chu et al. J Headache Pain. 2015; 16: 62. Chu et al. Cephalalgia. 2012;33(2):80 6.

21 Migraine and ischemic stroke Peng et al. Cephalalgia 2016, Epub ahead of print

22 Migraine and venous thromboembolism Accepted in Headache

23 Statistical model 2: Nested case-control control study Exposed Non exposed Exposure Comparison Migraine patients without stroke Exposed Non exposed Migraine patients with stroke

24 Triptan use and ischemic stroke Unpublished data

25 Nested-case control approach Strength and statistical model selection Short-term t exposure on outcome (e.g. drug) Exposure over different time interval Statistical correction of covariates

26 Implication from our studies Associated with Migraine with aura- all migraine specific c associationsat o s Cranial neuropathy Ischemic stroke related: CN3,4,6, CN5, Venous thromboembolism CN7, CN8 MA specifically Depression (not listed) Renal calculi (not listed) linked to vascular comorbidities?

27 Why vascular disease and MA? Central Hypertension (Schillaci, 2010) Vascular Comorbidity (Scher, 2005) Vascular Resistance (Schillaci, 2010 ) Poorer Patent Prothrombotic cholesterol foremen ovale state profile (Carod-Artal, 2006) (Hering-Hanit, 2001) (Scher, 2005)

28 Drug related studies Drug adherence (Triptan) PPI and headache Better when prescribed by Esomeprazole and neurologist lansoprazole increased Worse at local medical the risk of headache clinic i Chen et al. J Headache Pain. 2014;15:48. Liang et al. Cephalalgia. 2015;35:203-10

29 Summary

30 TED speaker / data analyst Kenneth Cukier Big data is better data

31 BUT JUNK IN JUNK OUT Methodology matters

32 Acknowledgement: My mentor: Prof. Shuu-Jiun Wang My fellow neurologist / photographer: Vincen Chuang, for all the Taiwan photos