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Part 3Studies Usin Automated Databases

- , , ,Center for Clinical Epidemiology and Biostatistics

University of Pennsylvaniac oo o e c ne

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Observational Studies

Key steps

Good study question

Forming a research team

Choice of data source

Defining study cohortChoice of study design

Defining outcomes

Obtain funding (optional)Data collection

Data analysis

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Publication

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data source:In atient out atient emer enc care

records

Behavioral factors (smoking, ETOH)

,

All laboratory (including pathology) andradiology tests

All prescribed and OTC medications

All components of data linkable arge o pa en s w o are popu a on-representative

Pa er chart review ossible

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Pharmacoepidemiology

Existed since 1980 in North America

EfficientInexpensive

Large sample sizeObviates recall bias

Not ood forIllnesses that do not come to medical attentionIllnesses that are poorly defined by diagnostic

codin s stems e. . Steven-Johnson S ndromeInpatient drug exposure (not included in some)Delayed drug exposure (patient may lost eligibility)

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. .,

Interested in Rx drugs not covered or OTC drugs

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Pharmacoepidemiology Databases

Claims Databases e ca ecor a a ases

In-between claims and medical record

Prescription information

Medical Diagnoses (included or linkable)

Missing or incomplete data elementsOTC medication (generally not available)

, ,available)

Laboratory and radiology data (incomplete)

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npa en recor s no ava a e or some

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Examples of Claims Databases

Joint state and federal funding that provide medical and prescription coverage to low-

income individuals

Medicare data Anyone >65 years is eligible

Pennsylvania Pharmaceutical Assistance Contract for the ElderlyData (State of Pennsylvania)

eligible but not poor enough to get Medicaid prescription coverage

Major advantages

Abilit to link dia nosis information with rescri tion data

Financial incentive means near complete prescriptioninformation

Ma or limitations:

Limited generalizability

Lack of behavioral and anthropometry data

uestionable validit of dia noses

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Limited number of drug categories and drugs covered OTC medication information missing

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Example using

Medicaid/Medicare Data

arrhythmia?

Study Design: Nested case-control

Study population: Medicaid enrollees

Cases: Patients with sudden cardiac death or

Controls: Selected using incidence density samplingmatched on eligible at-risk time before index date

Exposure: cisapride prescription obtained fromprescription coverage linked with Medicaid

CCEB Hennessy et al. Br J Clin Pharmacol 2008;66:375385

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.

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osteoporotic fracture risk?

Study population: Patients enrolled in

Exposure: Various classes of antiHTNs

Statistical analysis: Cox proportional hazard

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Solomon et al. JBMR 2011;26:15611567

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Solomon DH et al. JBMR 2011;26:15611567

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Examples of Medical Record Databases

Local University of Pennsylvania Health System (EPIC)

Geisinger Health System

Nation-wide General Practice Research Database (GPRD)

The Health Improvement Network (THIN)

AdvantagesDiagnoses can be validated easily (e.g., pathology)

ome e av ora an an ropome ry a a ava a e

Disadvantages

Local databases are hard to query for research

BMI and smoking information are often incomplete

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x use n ormat on ncomp ete or m ss ng

Costly computer hardware/software needed forGPRD

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prevalent colorectal adenoma risk?

-

Study population: Patients undergoing

Cases: Patient with at least 1 adenoma found

Exposure: Prior insulin use

regression

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Wong et al. Manuscript under review

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Insulin Therapy and

Colorectal Adenoma

Exposure

definitionsDuration of

Case Control Crude

OR

Adjusted

OR

Case Control Crude

OR

Adjusted

OR

insulin exposure

6 months[WH1] 49

(26%)

144

(22%)

1.2

(0.9-1.8)

1.3

(0.9-1.8)

14

(24%)

144

(22%)

1.1

(0.6-2.1)

1.2

(0.6-2.2)

12 months[WH2] 41

(23%)

124

(19%)

1.2

(0.8-1.8)

1.2

(0.8-1.8)

10

(19%)

124

(19%)

0.9

(0.5-1.9)

0.9

(0.5-2.0)

18 months 40

(22%)

92

(15%)

1.6

(1.1-2.4)

1.6

(1.1-2.5)

9

(17%)

92

(15%)

1.2

(0.5-2.4)

1.2

(0.6-2.5)

years

(19%) (13%)

.

(1.0-2.5)

.

(1.1-2.6) (15%) (13%)

.

(0.6-2.7)

.

(0.6-2.9)

3 years 23 43 2.0 2.0 6 43 1.6 1.7

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. - . . - . . - . . - .

[WH1]I assume the reference group is no insulin use. Exclude those with

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Potential MechanismsPotential Mechanisms Increased bacterial colonization with acidIncreased bacterial colonization with acid

suppressionsuppression

Direct immunosuppressive effect of PPIDirect immunosuppressive effect of PPI

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of community-acquired pneumonia (CAP)?

-

Study population: Adult GPRD population (1987-

Cases: Patient incident CAP

sampling, matching on practice site, calendar, - .

Exposure: Prior PPI exposure

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regression

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General Practice Research Database(GPRD)

Containing information on over 8 million

patients followed by GPsPatients are representative of the national

popu a on

Dx and Rx data are accurate and complete

Used in a variety of clinical studies

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Type of PPIType of PPIexposureexposure

CasesCases ControlsControls SexSex-- and Ageand Age--

adjusted ORadjusted OR

Adjusted ORAdjusted OR

(95% CI)(95% CI)

NonNon--useuse 73,187 (91.4)73,187 (91.4) 770,626 (96.3)770,626 (96.3) ReferenceReference ReferenceReference

CurrentCurrent

useuse

3,455 (4.3)3,455 (4.3) 10,031 (1.3)10,031 (1.3) 2.05 (1.962.05 (1.96--2.15)2.15) 1.02 (0.971.02 (0.97--1.08)1.08)

Past usePast use 3,424 (4.3)3,424 (4.3) 19,215 (2.4)19,215 (2.4) 1.50 (1.441.50 (1.44--1.56)1.56) 0.95 (0.900.95 (0.90--1.0)1.0)

us e or ma c ng ac ors prac ce s e, ca en ar year an ura on o o ow-up , sex, age a

index date, current smoking, alcoholism, total number of GP visits during the past year, total number

of hospitalizations during past year, CAP prior to GPRD enrollment, chronic obstructive pulmonary

disease or asthma, m ocardial infarction, con estive heart failure, chronic renal failure, cirrhosis,diabetes mellitus, stroke, any malignancies other than basal cell skin cancer and dementia, as well as

histamine type 2 receptor antagonist, anxiolytic, antidepressant, anti-parkinsonian drug, antipsychotic,

barbiturate, opiate, corticosteroid, antibiotic and non-steroidal anti-inflammatory drug use.

CCEB Sarkar et al.Annals of Internal Medicine. 2008;149:391-8.

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Type of PPI exposureType of PPI exposure Adjusted ORAdjusted OR

NonNon--useuse ReferenceReference

Daily doseDaily dose

1.5 DDD/day1.5 DDD/day 1.00 (0.951.00 (0.95--1.06)1.06)

>1.5 DDD/day>1.5 DDD/day

Duration of use before indexDuration of use before index

datedate

. .. . -- ..

1.74 (1.491.74 (1.49--2.03)2.03)

180 days

. .. . -- ..

0.91 (0.840.91 (0.84--0.97)0.97)


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(95% CI)(95% CI)

-

H2RA new starters

Within 14 days before index date 3.90 (3.183.90 (3.18--4.78)4.78)

Within 7 days before index dateWithin 2 days before index date

5.21 (4.005.21 (4.00--6.80)6.80)7.66 (5.197.66 (5.19--11.31)11.31)

Within 14 days before index date

Within 7 days before index date

3.16 (2.453.16 (2.45--4.08)4.08)

3.80 (2.703.80 (2.70--5.41)5.41)Within 2 days before index date 6.53 (3.956.53 (3.95--10.80)10.80)


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Combined claims and medical record databases

Kaiser Permanente Medical care program

Advantages

,

Stable membership

Comprehensive clinical and pharmacy informationlinked electronically

Outcome validation possible

ea nesses

Lack racial or socioeconomic information

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the risk of bladder cancer?

Study population: KPNC enrollee > 40 years with

Exposure: pioglitazone based on KPNC pharmacydatabase

Outcome: bladder cancer in KPNC cancer registry

patient telephone interview

Statistical anal sis: Cox re ression

CCEB Lewis JD et al. Diabetes Care 2011;34:916922

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CCEB Lewis JD et al. Diabetes Care 2011;34:916922

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Study question: Is PPI therapy associated the risk

of community-acquired pneumonia (CAP)?

Study Design: Nested case-control study Study population: Group Health enrollees > 65 yrs

Cases: Patient incident CAP by x-ray or trating

physician assessment Controls: selected using incidence density

samp ng, ma c ng on age, sex an ca en ar year

Exposure: current PPI exposure based on

Statistical analysis: Conditional logistic

CCEB Dublin et al. Pharmacoepidemiol Drug Saf. 2010;19(8): 792802

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CCEBDublin et al. Pharmacoepidemiol Drug Saf. 2010;19(8): 792802

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Logistical issues

Local collaboration generally necessary Kaiser Permanente

Grou Health Local Medical Records Database

Open but regulated access

GPRD (www.gprd.com) THIN (administered by EPIC www.epic-uk.org) PACE ma be

Data-specific considerations Nature of outcome or exposure (e.g., histologic diagnosis)

. .,guidelines)

Time periods of data (availability of OTC drugs) Possibility of data validation

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Availability of relevant data (e.g., smoking, alcohol, BMI)

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There is no single ideal database Each has its advantages and disadvantages

Validity of diagnosis is generally better in medical

Claims database can provide excellent prescriptionmedication information

Each has proven it can be useful for

pharmacoepidemiology research Appropriate choice depends on the study

question

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The St eps

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Documents