epidemiology and sex(ually transmitted diseases): the basics willard cates, jr., md, mph family...

Epidemiology and Sex(ually Transmitted Diseases):

The Basics

Willard Cates, Jr., MD, MPHFamily Health International

Principles of STD/HIV ResearchUniversity of Washington

Seattle, WashingtonJuly 22, 2002

ObjectivesObjectives

• To understand basic To understand basic definitions of epidemiologydefinitions of epidemiology•To describe components of To describe components of descriptive, observational and descriptive, observational and experimental epidemiologyexperimental epidemiology•To know advantages and To know advantages and disadvantages of case-control disadvantages of case-control and cohort designsand cohort designs

Cholera in London, 1854Cholera in London, 1854

The Etymology of The Etymology of EpidemiologyEpidemiology

epiepi == uponupon

demosdemos == peoplepeople

logylogy == study of study of

e.g. Population Level Sciencee.g. Population Level Science

Definition of EpidemiologyDefinition of Epidemiology

The study of the distribution The study of the distribution and determinants of disease and determinants of disease and health in human and health in human populations. populations.

Stedman’sStedman’s

EpidemiologyEpidemiology

The science of making the The science of making the obvious obscureobvious obscure

ClinicianClinician

EpidemiologyEpidemiology

II0 0 = = (480)(2)/10(480)(2)/1066/yr/yr

(9.1 x 0.955) + 0.045(9.1 x 0.955) + 0.045

The science of long divisionThe science of long division

StatisticianStatistician

EpidemiologyEpidemiology

The worst-taught course in The worst-taught course in medical schoolmedical school

Anonymous Med StudentAnonymous Med Student

EpidemiologyEpidemiology

The study of skin diseasesThe study of skin diseases

Atlanta NativeAtlanta Native

Epidemiology’sEpidemiology’sFundamental AxiomsFundamental Axioms

• Non-randomnessNon-randomness

• Etiologic thinkingEtiologic thinking

• PreventabilityPreventability

EpidemiologyEpidemiology

• Quantitative basic scienceQuantitative basic science

• Method of causal reasoningMethod of causal reasoning

• Vehicle for clinical and Vehicle for clinical and public health actionpublic health action

W. Cates, 1982

Exposure Variable – “E”Exposure Variable – “E”

• Characteristic of interestCharacteristic of interest

• Risk factor Risk factor

• Predictor variablePredictor variable

• Independent variableIndependent variable

• Putative causal factorPutative causal factor

Outcome or Disease Variable – Outcome or Disease Variable – “D”“D”

• Health event of interestHealth event of interest

• Illness, injury, infectionIllness, injury, infection

• Response variableResponse variable

• Dependent variableDependent variable

• Effect variableEffect variable

E-D Relationships – E-D Relationships – STD ExamplesSTD Examples

• Gonorrhea Gonorrhea –– PIDPID

• PID PID –– ectopic pregnancyectopic pregnancy

• Age Age –– chlamydia infectionchlamydia infection

• HPV HPV –– cervical cancer cervical cancer

• AlcoholAlcohol –– high risk behaviorhigh risk behavior

• Circumcision Circumcision – – HIV infectionHIV infection

Categories of Study DesignCategories of Study Design

• DescriptiveDescriptive

• AnalyticAnalytic

• ExperimentalExperimental

Knowledge ContinuumKnowledge Continuum

Less More

Descriptive Analytic

• Search for clues • Clues available

Most

Experimental

Descriptive StudiesDescriptive Studies

• Patterns of occurrencePatterns of occurrence

• No comparison groupNo comparison group

• Generate hypotheses Generate hypotheses about E-D relationshipsabout E-D relationships

Descriptive Studies: Descriptive Studies: Examples from Examples from STDSTD

• Epidemiology of chlamydia in Epidemiology of chlamydia in NorwayNorway

• Prevalence of sexual behaviors Prevalence of sexual behaviors among a sample of the general among a sample of the general populationpopulation

• Trends in the first 20 years of AIDS Trends in the first 20 years of AIDS in the US in the US

Analytic StudiesAnalytic Studies

• Test hypotheses about E-D Test hypotheses about E-D relationshipsrelationships

• Three main types:Three main types:–– CohortCohort–– Case-controlCase-control–– Cross-sectionalCross-sectional

Cohort Studies - OverviewCohort Studies - Overview

• Subjects selected on basis of ESubjects selected on basis of E

• Directionality always forwardDirectionality always forward–– E E DD

• TimingTiming–– Prospective: “real time”Prospective: “real time”

–– Retrospective: “historical time”Retrospective: “historical time”

Cohort Studies –Cohort Studies – Flow Chart Flow Chart

Source Population

Study Group E+

Study Group E

D+

D

D+

D

Cohort Studies: Cohort Studies: Major AdvantagesMajor Advantages

• Logical temporal sequenceLogical temporal sequence

• Can measure incidence of DCan measure incidence of D

• Well-suited for rare EWell-suited for rare E

• Can study many effects of one ECan study many effects of one E

Cohort Studies: Cohort Studies: Major DisadvantagesMajor Disadvantages

• Many subjects needed for rare DMany subjects needed for rare D

• Follow-up: logistics, lossesFollow-up: logistics, losses

• Prone to selection biasProne to selection bias

• Prospective: time-consuming, costly, Prospective: time-consuming, costly, observation can influence behaviorsobservation can influence behaviors

• Retrospective: suitable recordsRetrospective: suitable records

Case-Control Studies:Case-Control Studies:OverviewOverview

• Subjects selected on basis of Subjects selected on basis of DD

• Directionality is backward Directionality is backward –– DD EE

Case-Control Studies –Case-Control Studies – Flow Chart Flow Chart

Source Population

Cases D+

Controls D

E+

E

E+

E

Case-Control Studies: Case-Control Studies: Major AdvantagesMajor Advantages

• Quick and inexpensiveQuick and inexpensive

• Can study multiple ECan study multiple E

• Well-suited for rare D and D with Well-suited for rare D and D with long latencylong latency

• Requires fewer subjects at entryRequires fewer subjects at entry

Case-Control Studies: Case-Control Studies: Major DisadvantagesMajor Disadvantages

• Design “backward”Design “backward”

• Unsuitable for rare EUnsuitable for rare E

• Usually cannot measure D incidenceUsually cannot measure D incidence

• Temporal E-D uncertaintyTemporal E-D uncertainty

• Prone to selection and recall biasProne to selection and recall bias

Study Bias - Study Bias - A Further LookA Further Look

• Selection bias: differential selection of Selection bias: differential selection of participants on the basis of E or Dparticipants on the basis of E or D

• Information bias: differential collection Information bias: differential collection or classification of E or D among or classification of E or D among participantsparticipants

–– Recall bias: differential recall of Recall bias: differential recall of E E among cases and controls among cases and controls

Experimental Studies (1)Experimental Studies (1)

• Assign E Assign E randomlyrandomly, follow for D, follow for D

• If placebo, blinding possibleIf placebo, blinding possible

• Types:Types:

–– Clinical trialClinical trial

–– Community trialCommunity trial

Experimental Studies (2)Experimental Studies (2)

• Rolls Royce!Rolls Royce!

• Randomization controls extraneous Randomization controls extraneous variables, both known and unknownvariables, both known and unknown

• Limitations: ethical concerns, cost, Limitations: ethical concerns, cost, length, not feasible for rare Dlength, not feasible for rare D

Observational vs. Experimental: Observational vs. Experimental: A Tale of 2 StudiesA Tale of 2 Studies

StudyStudy DesignDesign

Zekeng, 1993Zekeng, 1993 Observational/CohortObservational/Cohort

Roddy, 1998Roddy, 1998 ExperimentalExperimental

• Both were conducted in the same network Both were conducted in the same network of Cameroon sex workersof Cameroon sex workers

• Both examined use of N-9 and HIV Both examined use of N-9 and HIV acquisitionacquisition

Initial Analysis of Initial Analysis of Observational StudyObservational Study

Rate of HIV (per 100 women years)Rate of HIV (per 100 women years)

Inconsistent users Inconsistent users 16.316.3Consistent usersConsistent users 3.5 3.5

Rate RatioRate Ratio 0.2 (0.1 – 0.7)0.2 (0.1 – 0.7)

Source: Zekeng (1993)

Data Source: Coital diaries from sex Data Source: Coital diaries from sex workersworkers

Measure: Efficacy per sexual episodeMeasure: Efficacy per sexual episode

Result:Result: Condoms Condoms 92% (79-100%) 92% (79-100%)N-9 Suppositories 100% (43-N-9 Suppositories 100% (43-

100%)100%)

Reanalysis of Reanalysis of Observational StudyObservational Study

Sources: Zekeng (1993), Wittkowski (1998)Sources: Zekeng (1993), Wittkowski (1998)

ZekengZekeng RoddyRoddy

AnalysisAnalysis ObservationalObservational ObservationalObservational

Rates of HIV:Rates of HIV:Inconsistent use 16.3Inconsistent use 16.3 15.615.6Consistent useConsistent use 3.5 3.5 5.0 5.0

Rate RatiosRate Ratios 0.2 (0.1-0.7) 0.2 (0.1-0.7) 0.3(0.1-0.7) 0.3(0.1-0.7)

Observational Analysis Observational Analysis

of the 2 N-9 Studiesof the 2 N-9 Studies

Sources: Zekeng (1993), Roddy (1998)Sources: Zekeng (1993), Roddy (1998)

RoddyRoddy RoddyRoddy

AnalysisAnalysis ObservationalObservational ExperimentalExperimental

Rates of HIV:Rates of HIV:Inconsistent use Inconsistent use 15.6 15.6 PlaceboPlacebo 4.34.3Consistent useConsistent use 5.0 5.0 N-9N-9 5.35.3

Rate RatiosRate Ratios 0.3 (0.1-0.7) 0.3 (0.1-0.7) 1.2(0.7-2.1)1.2(0.7-2.1)

Observational vs. Experimental Analysis, Observational vs. Experimental Analysis,

Same N-9 StudySame N-9 Study

Source: Roddy (1998)

Study Design:Study Design:Concluding RemarksConcluding Remarks

• Must consider:Must consider:–– Objectives of studyObjectives of study–– Current knowledge about E-DCurrent knowledge about E-D–– Ethical issuesEthical issues–– Time, money, human resourcesTime, money, human resources

• Different approachesDifferent approaches

• Flexibility and creativity are KEY!Flexibility and creativity are KEY!

Uses of Epidemiology:Uses of Epidemiology:Levels of EvidenceLevels of Evidence

Quality of EvidenceQuality of Evidence

I.I. Good evidenceGood evidence-- large RCT, large RCT, -- primary outcomesprimary outcomes

II.II. Fair evidenceFair evidence-- observational studies,observational studies,-- surrogate outcomessurrogate outcomes

III.III. Weak evidenceWeak evidence-- anecdotes, anecdotes, -- expert opinionexpert opinion

Strength of RecommendationStrength of Recommendation

A.A. StrongerStronger-- important benefits,important benefits,-- broadly applicablebroadly applicable

B.B. Weaker Weaker -- smaller benefit,smaller benefit,-- limited generalizabilitylimited generalizability

C.C. Insufficient evidenceInsufficient evidence-- expert opinionexpert opinion