epidemiologic study design and data analysis

8/3/2019 Epidemiologic Study Design and Data Analysis

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Epidemiologic Study Design andEpidemiologic Study Design and

Data AnalysisData Analysis

Shelley Harris, Ph.D.Shelley Harris, Ph.D.

Associate ProfessorAssociate Professor

Department of Epidemiology and Community Health &Department of Epidemiology and Community Health &

Center for Environmental StudiesCenter for Environmental Studies

[email protected]@vcu.edu

BIOINFORMATICS TECHNOLOGIES

LFSC520

OutlineOutline

Introduction to epidemiologyIntroduction to epidemiology

Study designs and measures of risk inStudy designs and measures of risk inepidemiologyepidemiology

Statistical Analysis programsStatistical Analysis programs

Epidemiological Analysis programsEpidemiological Analysis programs

An example calculation ..An example calculation ..

Some cautionsSome cautions

Shelley A.Harris

Digitally signed by Shelley A. HarrisDN: CN = Shelley A. Harris, C = US, O= VCUReason: I am the author of thisdocumentDate: 2005.02.02 16:42:43 -05'00'


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Introduction to EpidemiologyIntroduction to Epidemiology

EpidemiologyEpidemiology is the study of patterns ofis the study of patterns of

disease occurrence and other healthdisease occurrence and other health--

related conditions in human populationsrelated conditions in human populations

and of the factors that influence theseand of the factors that influence these

occurrences and conditions.occurrences and conditions.

Leading Causes of DeathLeading Causes of Death

Percent of Total Deaths

US data/Adapted from Cancer Journal for Clinicians, 1994.

33.5%

Hea

rt

Dis

ease

s

Acci

dents

Cer

ebro

vasc

ular

Dis

ease

s

Can

cer

23.5%

6.7%4.3% 4.0% 3.7%

2.2%1.4% 1.2% 1.2%1.2%

Dia

betes

Chr

onic

Obs

tructive

Lung

Dis

ease

s

Pneu

mon

ia&

Influ

enza

Suic

ide

Cirr

hosi

sof

Live

r

HIV

Infe

ction

Hom

icide


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Male Cancer StatisticsMale Cancer Statistics

Estimated incidenceEstimated incidence Estimated deathsEstimated deaths

Melanoma of skinMelanoma of skin

OralOral

LungLung

PancreasPancreas

StomachStomach

Colon & RectumColon & Rectum

ProstateProstate

UrinaryUrinary

Leukemia & LymphomasLeukemia & Lymphomas

All othersAll others

3%3%

3%3%

16%16%

2%2%

2%2%

12%12%

32%32%

9%9%

7%7%

14%14%



OralOral

LungLung

PancreasPancreas

StomachStomach


ProstateProstate

UrinaryUrinary



2%

2%

33%

4%

3%

10%

13%

5%

8%

20%


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1%1%

1%1%

18%18%

23%23%

5%5%

11%11%

5%5%

4%4%

3%3%

8%8%

21%21%

Female Cancer StatisticsFemale Cancer Statistics

Estimated incidenceEstimated incidence Estimated deathsEstimated deaths


OralOral

BreastBreast

LungLung

PancreasPancreas


OvaryOvary

UterusUterus

UrinaryUrinary



3%3%

2%2%

32%32%

13%13%

2%2%

13%13%

4%4%

8%8%

4%4%

6%6%

13%13%



OralOral

BreastBreast

LungLung

PancreasPancreas


OvaryOvary

UterusUterus

UrinaryUrinary



A report from the National Cancer InstituteA report from the National Cancer Institute

(NCI) estimates that about 1 in 8 women in(NCI) estimates that about 1 in 8 women in

the United States (approximately 12.8the United States (approximately 12.8

percent) will develop breast cancer duringpercent) will develop breast cancer during

her lifetime.her lifetime.


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Descriptive EpidemiologicDescriptive EpidemiologicStudiesStudies

correlational or ecologic studiescorrelational or ecologic studies

used to determine patterns of disease orused to determine patterns of disease or

disability across different populations,disability across different populations,

geographical areas and timegeographical areas and time


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Breast CancerBreast CancerInternational incidence ratesInternational incidence rates (per 100,000(per 100,000

women)women)

Adapted from International Opportunities in Cancer Management, SRI International, 1994.

129.5129.5

108.8108.8 108.6108.6 106.8106.8

94.394.3

84.384.376.476.4

60.160.1

37.037.0

SwedenSweden USUS ItalyItaly NetherlandsNetherlands UnitedUnited FranceFrance GermanyGermany SpainSpain JapanJapanKingdomKingdom

Breast Cancer Rates in American Women


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Breast Cancer Rates

0 5 10 15 20 25 30 35

Thailand

China

Japan

Hong Kong

USSR

Singapore

Spain

France

Australia

United States

Canada

New Zealand

Denmark

England & Wales

Rate/10000

Ecological or CorrelationalEcological or Correlational

StudiesStudiesgenerally inexpensive and quickgenerally inexpensive and quick

substantial international and temporal variationssubstantial international and temporal variations

relate observed differences in the morbidity orrelate observed differences in the morbidity or

mortality to the spatial and temporal distributionmortality to the spatial and temporal distribution

of risk factorsof risk factors

living habits, genetic composition of groups,living habits, genetic composition of groups,

occupational or environmental exposuresoccupational or environmental exposures


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Ecological StudiesEcological Studies-- BreastBreast

Cancer?Cancer?

0

5

10

15

20

25

30

35

40

45

50

Rate of Breast Cancer 25 20 18 17 15 10 7

Per Capita Consumption of Beer 50 40 40 35 30 26 24

Austral ia Germany Hol land England France CanadaUnited

States

Ecological StudiesEcological Studies-- HeartHeart

DiseaseDisease

0

5

10

15

20

25

30

35

40

45

50

Rate of Heart Disease 7 10 15 17 18 20 25

Per Capita Consumption of Beer 50 40 40 35 30 26 24

Austral ia Germany Hol land England France CanadaUnited

States


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Sperm Counts over time (years)

R2

= 0.9793

0

2

4

6

8

10

0 1 2 3 4 5 6 7 8

Year

S

erm

C

ounts(x

10

6)


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Popular Hypotheses:Popular Hypotheses:

Exposure toExposure to syntheticsyntheticenvironmental estrogens isenvironmental estrogens is

related to:related to:

1) increases of breast and prostate cancer over time1) increases of breast and prostate cancer over time

2) differences in rates of breast and prostate cancer2) differences in rates of breast and prostate cancer

between countiesbetween counties

3) decreases in sperm quality/quantity observed over3) decreases in sperm quality/quantity observed over

the last 50 yearsthe last 50 years

Exposure toExposure to naturalnaturalenvironmental estrogensenvironmental estrogens

accounts for:accounts for:

1) differences in rates of breast and prostate cancer1) differences in rates of breast and prostate cancer

between counties and differences in heart diseasebetween counties and differences in heart disease

AnAn ecological fallacyecological fallacyis defined as:is defined as:

The bias that may occur because an associationThe bias that may occur because an association

observed between variables on a group level doesobserved between variables on a group level does

not necessarily represent the association thatnot necessarily represent the association that

exists at an individual level.exists at an individual level.


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Geographic InformationGeographic Information

SystemsSystemsAn organized collection ofAn organized collection ofcomputer hardware,computer hardware,

software, geographicsoftware, geographic

data, and personneldata, and personnel

designed to efficientlydesigned to efficiently

capture, store,capture, store,

manipulate, analyze, andmanipulate, analyze, and

display all forms ofdisplay all forms of

geographically referencedgeographically referenceddatadata

Breast CancerBreast Cancer

--

SociodemographicSociodemographic and Lifestyleand Lifestylesociodemographicsociodemographic

SESSES 1.11.1--2x2x (high / low)(high / low)

Marital statusMarital status 1.11.1--2x2x (never / ever)(never / ever)

ResidenceResidence 1.11.1--2x2x (urban / rural)(urban / rural)

Race/ethnicityRace/ethnicity 1.11.1--2x2x (white,(white, hispanichispanic // asianasian))

ReligionReligion 1.11.1--2x2x (Jewish / Mormon)(Jewish / Mormon)

lifestyle factorslifestyle factors

Diet (high fat) ?Diet (high fat) ? Obesity/body shape??Obesity/body shape??

high alcohol consumption??high alcohol consumption?? low physical activity??low physical activity??

Smoking, passive smoke???Smoking, passive smoke???


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Established/Suspected BreastEstablished/Suspected Breast

Cancer Risk FactorsCancer Risk Factors

Age > 50: 4xAge > 50: 4x

Family history of disease: 1 relativeFamily history of disease: 1 relative premenopausalpremenopausal or 2or 2

relatives with any form: 4xrelatives with any form: 4x

History of benign breast disease: 4xHistory of benign breast disease: 4x

BRCA1 or BRCA2 mutation: 4xBRCA1 or BRCA2 mutation: 4x

Ionizing radiation (Ionizing radiation (espesp b/w puberty and 20 yrs): 2b/w puberty and 20 yrs): 2--4x4x

Lifetime exposure to estrogenLifetime exposure to estrogenLifestyle factors?Lifestyle factors?

Environmental factors?Environmental factors?

Lifetime exposure to estrogenLifetime exposure to estrogen

early menarche:early menarche: 1.11.1--2x2x (11 / 15)(11 / 15)

NulliparityNulliparity:: 1.11.1--3x3x ((nulliparousnulliparous // parousparous))

late age of first birth:late age of first birth: 1.11.1--3x (>30 / 30 /


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SuspectedSuspected

Environmental/OccupationalEnvironmental/OccupationalCauses of Breast CancerCauses of Breast Cancer

1)1) Low level ionizing radiationLow level ionizing radiation

2)2) Solvent exposuresSolvent exposures

3)3) Electromagnetic fields (EMF)Electromagnetic fields (EMF)

4)4) OrganochlorineOrganochlorine compoundscompounds

5)5) PesticidesPesticides

Analytic StudiesAnalytic Studies

To test hypotheses it is necessary to conductTo test hypotheses it is necessary to conduct

analytic epidemiological studies. Analyticanalytic epidemiological studies. Analytic

studies can be divided into two main types:studies can be divided into two main types:

1) Experimental studies1) Experimental studies -->> Clinical trialsClinical trials

2) Observational Studies2) Observational Studies


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The Epidemiologic Study

Controlled Assignment Uncontrolled Assignment

Experimental Studies

Non Randomized Randomized Sampling with Regard Sampling with RegardAssignment Assignment To Disease or Effect To Exposure, Characteristic,

Or Cause

Exposure or Characteristic History of ExposureAt Time of Study or Characteristic Prior

to Time of Study

Observational Studies

Clinical Trials(Efficacy, Effectiveness)

Community Trials Cross-sectional and/or Retrospective Studies

Prospective studies(cohort, case-cohort)

Cross-sectional StudiesRetrospective Studies

(Case-control)

CaseCase--Control StudiesControl Studies

selected into a study based on theirselected into a study based on their

disease status.disease status.

sometimes called retrospective studies orsometimes called retrospective studies or

casecase--referentreferent

most common type of epidemiologic studymost common type of epidemiologic study


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CaseCase--Control StudiesControl Studies

2001

ProspectiveRetrospective

1960 2030

In 2001 select

case and controlgroups

Follow back in timeto determineexposure status

Measures of Risk or AssociationMeasures of Risk or Association

Cases Controls Totals

Exposed a b M1

Not exposed c d M2

Totals N1 N2 N

Odds Ratio (OR)

= (a/b) / (c/d)

Odds of being a case if you are exposed = a/b

Odds of being a case if you are not exposed = c/d


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Self-reported

pesticide exposure

Breast Cancer

Yes No Totals

Yes 499 462 961

No 19 56 75

Totals 518 518 1036

Odds Ratio (OR) = (499 / 462) / (19 / 56)

= 3.18

Cohort StudiesCohort Studies

considered a natural experimentconsidered a natural experiment

called followcalled follow--up studies, incidenceup studies, incidence

studies, or longitudinal studiesstudies, or longitudinal studies

1)1) Prospective cohortProspective cohort

2)2) Retrospective cohortRetrospective cohort


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Cohort StudiesCohort Studies

2005

ProspectiveRetrospective

exposed and

groups

exposed and

groups

exposed and

groups

exposed and

groups

exposed and

groups

non-exposedgroups

In 2005 select

1960

non-exposed

In 2005 select

2030

Measures of RiskMeasures of Risk

Disease No Disease Totals

Exposed a b M1

Not exposed c d M2

Totals N1 N2 N

Rate of disease in exposed = a/(a+b) = a/M1

Rate of disease in non-exposed = c/(c+d) = c/M2

Relative risk = (a/M1) (c/M2)


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[PCBs] in blood

Breast cancer

Yes No Totals

High 20 9980 10000

Low 5 9995 10000

Totals 25 19975 20000

Relative Risk (RR) = (20 / 10,000) / (5 / 10,000)

= 4.0

Established EnvironmentalEstablished Environmental

Causes of Breast CancerCauses of Breast Cancer

1)1) Ionizing radiationIonizing radiation


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Some Statistical Analysis SoftwareSome Statistical Analysis Software

SASSAS

SPSSSPSS

SYSTATSYSTAT

SPLUSSPLUS

SASSAS is a large, generalis a large, general--purpose package descendedpurpose package descendedfrom an original program that was designed to run onfrom an original program that was designed to run onmainframe computers in a "batch" mode,mainframe computers in a "batch" mode, ieie. by the user. by the usersubmitting a batch of commands and then getting a pilesubmitting a batch of commands and then getting a pileof results in a separate output file (or window, now thatof results in a separate output file (or window, now thatWindows and Mac versions are available). Along with aWindows and Mac versions are available). Along with aslightly complicated approach to data management, thisslightly complicated approach to data management, thismakes the program harder to learn and comparedmakes the program harder to learn and comparedwith SPSS there is less capability to learn by experimentwith SPSS there is less capability to learn by experimentusing menus. On the other hand, the data processingusing menus. On the other hand, the data processing

capabilities are extremely powerful and the range ofcapabilities are extremely powerful and the range ofstatistical procedures wide.statistical procedures wide.

University of MelbourneUniversity of Melbourne


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SPSSSPSS is a wellis a well--known package particularlyknown package particularlypopular in the social sciences and psychology. Itpopular in the social sciences and psychology. Itis a very large and somewhat cumbersomeis a very large and somewhat cumbersomeprogram but also very powerful and capable ofprogram but also very powerful and capable ofperforming almost all the standard methods ofperforming almost all the standard methods ofanalysis. Recent Windows versions have aanalysis. Recent Windows versions have aconvenient user interface, but it can still be hardconvenient user interface, but it can still be hardto keep track of exactly what you've done. Theto keep track of exactly what you've done. Themenumenu--based interface makes it relatively easy tobased interface makes it relatively easy tolearn, at least for simple applicationslearn, at least for simple applications


SS--PLUSPLUS is a program for specialist statisticiansis a program for specialist statisticians

only. It is an interactive, objectonly. It is an interactive, object--oriented system,oriented system,

with both a wide range of builtwith both a wide range of built--in functions andin functions and

complete programming capabilities for extendingcomplete programming capabilities for extending

these. Probably its most useful feature for us isthese. Probably its most useful feature for us is

an extremely powerful and relatively easyan extremely powerful and relatively easy

--toto

--useuse

capacity for graphics.capacity for graphics.



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Epidemiological AnalysisEpidemiological Analysis

SoftwareSoftware

EpiEpi InfoInfo (free)(free) http://http://www.cdc.gov/epiinfowww.cdc.gov/epiinfo

PEPIPEPI (not so free)(not so free)

EGRETEGRET (not free)(not free)

EpiEpi InfoInfo

Latest Version:Latest Version: EpiEpi Info Version 3.3Info Version 3.3

WithWith EpiEpi Info and a personal computer, epidemiologists and otherInfo and a personal computer, epidemiologists and otherpublic health and medical professionals can rapidly develop apublic health and medical professionals can rapidly develop aquestionnaire or form, customize the data entry process, and entquestionnaire or form, customize the data entry process, and entererand analyze data. Epidemiologic statistics, tables, graphs, andand analyze data. Epidemiologic statistics, tables, graphs, and mapsmapsare produced with simple commands such as READ, FREQ, LIST,are produced with simple commands such as READ, FREQ, LIST,TABLES, GRAPH, and MAP.TABLES, GRAPH, and MAP. EpiEpi Map displays geographic mapsMap displays geographic mapswith data fromwith data from EpiEpi Info.Info.

A new version,A new version, EpiEpi Info for Windows retains many features of theInfo for Windows retains many features of the

familiarfamiliarEpiEpi Info for DOS, while offering Windows ease of useInfo for DOS, while offering Windows ease of usestrengths such as pointstrengths such as point--andand--click commands, graphics, fonts, andclick commands, graphics, fonts, andprinting.printing.

http://http://www.cdc.gov/epiinfowww.cdc.gov/epiinfo//


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EgretEgret

Egret software is a statistical package that specializes in offEgret software is a statistical package that specializes in offering modeling andering modeling andgraphics capabilities to investigators conducting epidemiologicagraphics capabilities to investigators conducting epidemiological and biomedicall and biomedicalstudies. Egret is a userstudies. Egret is a user--friendly statistical package for epidemiologists.friendly statistical package for epidemiologists.

Comprehensive Set of Models: Many Not Available ElsewhereComprehensive Set of Models: Many Not Available Elsewhere Contingency TablesContingency Tables

Logistic RegressionLogistic Regression

Conditional Logistic Regression*Conditional Logistic Regression*

Logistic Regression with Random EffectsLogistic Regression with Random Effects

BetaBeta--Binomial RegressionBinomial Regression

Poisson RegressionPoisson Regression

WeibullWeibull Regression Exponential RegressionRegression Exponential Regression

Cox Proportional Hazards RegressionCox Proportional Hazards Regression

Cox Regression with TimeCox Regression with Time--Dependent CovariatesDependent Covariates

KaplanKaplan--Meier Analysis and PlotsMeier Analysis and Plots

Extensive PostExtensive Post--Fit Analysis with Plots, Including DeltaFit Analysis with Plots, Including Delta--Betas, and Hazard FunctionsBetas, and Hazard FunctionsPlus a new spreadsheetPlus a new spreadsheet--based data editor and a statistical scratchpadbased data editor and a statistical scratchpad

Unlike other epidemiology software, Egret permits the case/contrUnlike other epidemiology software, Egret permits the case/control ratio to vary over strataol ratio to vary over stratawithout using an approximation for the conditional likelihood fuwithout using an approximation for the conditional likelihood function.nction.

Cancer: Surveillance, EpidemiologyCancer: Surveillance, Epidemiologyand End Resultsand End Results

The SEER Cancer Statistics reports,The SEER Cancer Statistics reports,

publications, publicpublications, public--use data and analysisuse data and analysis

software are available at the Nationalsoftware are available at the National

Cancer Institute web site:Cancer Institute web site:

http://http://SEER.Cancer.GovSEER.Cancer.Gov//


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SEERSEER The small printThe small print

PC Software to Calculate Statistics from SEER and Other Data SouPC Software to Calculate Statistics from SEER and Other Data Sourcesrces

SEER*StatSEER*Stat statistical software can be used to view individual cancer recostatistical software can be used to view individual cancer records orrds orcalculate incidence, mortality, survival, and prevalence statistcalculate incidence, mortality, survival, and prevalence statistics from SEER andics from SEER andother cancerother cancer--related databases. All variables in the SEER publicrelated databases. All variables in the SEER public--use data areuse data areavailable for analysis. Statistics calculated in SEER*Stat can bavailable for analysis. Statistics calculated in SEER*Stat can be viewed, printed, ore viewed, printed, orexported for further analysis using other statistical software,exported for further analysis using other statistical software, including thoseincluding thosedescribed below.described below.

JoinpointJoinpoint is statistical software for the analysis of trends using modelsis statistical software for the analysis of trends using models with severalwith severaldifferent lines that are connected at the "different lines that are connected at the "joinpointsjoinpoints." The software takes trend data." The software takes trend data(e.g., cancer rates) and fits the simplest(e.g., cancer rates) and fits the simplestjoinpointjoinpoint model that the data allow.model that the data allow. JoinpointJoinpointis often used to analyze trends in rates calculated by SEER*Statis often used to analyze trends in rates calculated by SEER*Stat..

DevCanDevCan software usessoftware uses lifetablelifetable methods to compute the lifetime and agemethods to compute the lifetime and age--conditionedconditionedprobability of developing cancer and dying of cancer in the geneprobability of developing cancer and dying of cancer in the general population. Inputral population. Inputdata for the computations include cancer incidence and mortalitydata for the computations include cancer incidence and mortality rates as well as allrates as well as all--cause mortality rates. Data sets are supplied to estimate riskscause mortality rates. Data sets are supplied to estimate risks of developing andof developing anddying of cancer for over 20 cancer sites by race and sex. In adddying of cancer for over 20 cancer sites by race and sex. In addition,ition, DevCanDevCan can becan beused to calculate the lifetime risk using rates calculated in SEused to calculate the lifetime risk using rates calculated in SEER*Stat and exportedER*Stat and exportedfor use infor use in DevCanDevCan..

Class exerciseClass exercise see handoutssee handouts

Sample size calculation using:Sample size calculation using:

1) Hand calculation1) Hand calculation

2) Web2) Web--based free program (find yourbased free program (find your

own)own)

3) Examples in EXCEL and SAS3) Examples in EXCEL and SAS


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True DifferencePresent Absent

Conclusion ofStatistical Test

Different Correct(true positive)(1-=Power)

Incorrect:Type I () error(false positive)

Not Different Incorrect:Type II ( ) error(false negative)

Correct(true negative)

Power

Ho

Ho

n=100

n=1000

alpha

beta


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Sample SizeSample Size

nk

p q Z Z

p p=

+

+

11

2

2

1 2

2

_ _

/( )

( )

CRAP Detector #1CRAP Detector #1

Beware the large sample size.Beware the large sample size.

Effects can be statistically significant andEffects can be statistically significant andbiologically inconsequentialbiologically inconsequential

CRAP.: Circular Reasoning or AntiCRAP.: Circular Reasoning or Anti--intellectual Pomposityintellectual Pomposity


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CRAP Detector #2CRAP Detector #2

Beware the small sample sizeBeware the small sample size

It is hard to find significant differences and noIt is hard to find significant differences and no

difference means nothing.difference means nothing.

Some ThoughtsSome Thoughts

garbage in garbage out.garbage in garbage out.

consult the biostatistician and theconsult the biostatistician and the

epidemiologistepidemiologist

we charge by the hourwe charge by the hour

epidemiologic study design and data analysis

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