Overview of Overview of Study DesignsStudy Designs

Study DesignsStudy Designs

Experimental

Randomized Controlled Trial

Group Randomized

Trial

Observational

Descriptive Analytical

Cross-sectional

Ecological

Cohort

Case-control

Experimental v. Experimental v. ObservationalObservational

““Gold Standard”Gold Standard” Investigator Investigator

controls controls exposureexposure

Less commonLess common

Investigator Investigator observes observes exposuresexposures

Most commonMost common

4

INTERVENTION GROUP

OUTCOMEASSESSMENT

Present Future

TIME

Experimental Study: Experimental Study: Randomized Controlled Randomized Controlled

TrialTrial

Randomly Assigns

Intervention

Comparison

Randomized Controlled Randomized Controlled TrialTrial

Randomization is random distribution Randomization is random distribution or allocation of subjects into groupsor allocation of subjects into groups Treatment or intervention groupTreatment or intervention group Comparison group (placebo, another tx, no Comparison group (placebo, another tx, no

tx, usual care)tx, usual care) Helps ensure that both groups are Helps ensure that both groups are

similar re: known and unknown factorssimilar re: known and unknown factors Two types of RCTsTwo types of RCTs

Preventive trialsPreventive trials Therapeutic trialsTherapeutic trials

Group Randomized TrialGroup Randomized Trial

Unit of assignment = groupUnit of assignment = group Unit of analysis = individual Unit of analysis = individual

(usually)(usually) Investigator controls exposure statusInvestigator controls exposure status

Randomly assigns group to intervention Randomly assigns group to intervention groupgroup

Exposure assessed Exposure assessed beforebefore outcome outcome

7

Experimental StudyExperimental Study

StrengthsStrengths Able to Able to

demonstrate causal demonstrate causal associationassociation

Randomization Randomization deals with known deals with known and unknown and unknown confoundersconfounders

Investigators Investigators directly control directly control interventionintervention

LimitationsLimitations Ethical concerns Ethical concerns

(equipoise)(equipoise) Gen practice ≠ Gen practice ≠

artificial artificial ExpensiveExpensive Power often an Power often an

issueissue

Observational StudiesObservational Studies Most common, by necessityMost common, by necessity Observes nature without interventionObserves nature without intervention

Takes advantage of people’s natural Takes advantage of people’s natural exposures (choice, occupation, environment, exposures (choice, occupation, environment, residence)residence)

Collect data and statistically analyze Collect data and statistically analyze resultsresults Goal is to “mimic” experimental studyGoal is to “mimic” experimental study Statistics more important and usually more Statistics more important and usually more

complexcomplex Can be descriptive or analyticCan be descriptive or analytic

Study DesignsStudy Designs

Experimental

Randomized Controlled Trial

Group Randomized

Trial

Observational

Descriptive Analytical

Cross-sectional

Ecological

Cohort

Case-control

Cohort StudiesCohort Studies Two ways to assemble cohort:Two ways to assemble cohort:

Group of individuals with common Group of individuals with common characteristic or experience (then assess characteristic or experience (then assess exposure exposure beforebefore outcome) outcome)

Select subjects without outcome according Select subjects without outcome according to exposure status (esp important for rare to exposure status (esp important for rare exposure)exposure)

Followed over time to determine Followed over time to determine incidence of symptoms, disease, or deathincidence of symptoms, disease, or death

Analysis focuses on risk of outcome in Analysis focuses on risk of outcome in exposed compared to unexposed groupsexposed compared to unexposed groups Unexposed is referent or comparison groupUnexposed is referent or comparison group

Prospective Cohort Prospective Cohort StudiesStudies

Only include outcome-free individualsOnly include outcome-free individuals At risk of developing outcomeAt risk of developing outcome

Followed into future to observe Followed into future to observe outcomesoutcomes Can take long time to completeCan take long time to complete Important to re-assess exposures over time Important to re-assess exposures over time

Useful design for rare exposuresUseful design for rare exposures Not for rare outcomesNot for rare outcomes

Advantage: exposure assessed before Advantage: exposure assessed before subject knows outcome status; temporal subject knows outcome status; temporal sequencesequence

12

EXPOSURE ASSESSMENT

OUTCOMEASSESSMENT

Present Future

TIME

Prospective Cohort StudyProspective Cohort Study

Exposed

Unexposed

Retrospective Cohort Retrospective Cohort StudiesStudies

Both exposure and outcome occur before Both exposure and outcome occur before studystudy Studies only prior outcomesStudies only prior outcomes

Historical cohort reconstructed from Historical cohort reconstructed from existing data sources before study beginsexisting data sources before study begins

Example: Effects of pesticide exposure on Example: Effects of pesticide exposure on cancer mortality (cohort of factory workers cancer mortality (cohort of factory workers employed by manufacturer identified from employed by manufacturer identified from personnel records)personnel records)

Need good records with info on many Need good records with info on many variablesvariables

Sometimes good outcome info not availableSometimes good outcome info not available

14

EXPOSURE ASSESSMENT

OUTCOMEASSESSMENT

Past PresentTIME

Retrospective Cohort StudyRetrospective Cohort Study

Exposed

Unexposed

15

Cohort StudyCohort Study

StrengthsStrengths Easier to Easier to

differentiate cause differentiate cause from effectfrom effect

Direct estimation of Direct estimation of incidenceincidence

Able to examine Able to examine multiple outcomesmultiple outcomes

Efficient for rare Efficient for rare exposuresexposures

ProspectiveProspective Reduces recall biasReduces recall bias

LimitationsLimitations Large sample sizeLarge sample size ProspectiveProspective

Long-term follow-upLong-term follow-up ExpensiveExpensive

Case-Control StudiesCase-Control Studies Both exposure and outcome have Both exposure and outcome have

occurredoccurred Classified according to outcome status Classified according to outcome status

beforebefore exposure ascertained exposure ascertained Cases with outcome selected from well-Cases with outcome selected from well-

defined source populationdefined source population Controls without outcome* sampled Controls without outcome* sampled

from population that produced casesfrom population that produced cases Analysis focuses on odds of Analysis focuses on odds of exposureexposure

in cases compared to controlsin cases compared to controls

Case-Control StudyCase-Control Study Grouped on basis of past or current Grouped on basis of past or current

outcomeoutcome Outcome already occurred before Outcome already occurred before

exposure assessedexposure assessed May lead to biased recallMay lead to biased recall May be difficult to establish temporalityMay be difficult to establish temporality

Useful design for rare outcomesUseful design for rare outcomes Not for rare exposuresNot for rare exposures

Advantages: Advantages: Less expensive than cohort (usually)Less expensive than cohort (usually) Can look at multiple exposuresCan look at multiple exposures

18

EXPOSURE ASSESSMENT

OUTCOMEASSESSMENT

Past Present

TIME

Case-Control StudyCase-Control Study

Cases(with outcome)

Controls(without outcome)*

19

Case-Control StudyCase-Control Study

StrengthsStrengths Efficient for rare Efficient for rare

outcomesoutcomes Able to examine Able to examine

multiple exposuresmultiple exposures

LimitationsLimitations ↑ ↑ possibility of biaspossibility of bias Temporal Temporal

associationassociation Inefficient for rare Inefficient for rare

exposuresexposures

Cross-Sectional StudiesCross-Sectional Studies

Study population not selected based Study population not selected based on outcome or exposure statuson outcome or exposure status

Outcome and exposure assessed at Outcome and exposure assessed at same timesame time

Snapshot at single point in timeSnapshot at single point in time Problems inferring temporal sequenceProblems inferring temporal sequence Identify prevalent cases of long Identify prevalent cases of long

durationduration

21

EXPOSURE ASSESSMENT

OUTCOMEASSESSMENT

Past Present

TIME

Analytical Cross-Sectional Analytical Cross-Sectional StudyStudy

Exposed

Unexposed

22

Cross-Sectional StudyCross-Sectional Study

StrengthsStrengths Less time and Less time and

resources resources No follow-up time No follow-up time

involvedinvolved More representative More representative

of well-defined of well-defined general populationgeneral population

Useful when onset is Useful when onset is difficult to establish difficult to establish (incidence)(incidence)

LimitationsLimitations Temporal Temporal

associationassociation Potential for Potential for

prevalence-prevalence-incidence biasincidence bias

Not for rare Not for rare exposures or exposures or outcomesoutcomes

Reverse causalityReverse causality

23

EXPOSURE ASSESSMENT

OUTCOMEASSESSMENT

Past PresentTIME

Analytical Ecological StudyAnalytical Ecological Study

Exposed

Unexposed

Note: Often in ecological studies, the exposures and outcomes are continuous measures

24

Ecological StudyEcological Study StrengthsStrengths

Relatively quick and Relatively quick and inexpensiveinexpensive

May be only appropriate May be only appropriate design for research design for research questionquestion

May be useful when May be useful when intra-group variability in intra-group variability in exposure is small exposure is small

May provide greater May provide greater inter-group variability inter-group variability across larger ecological across larger ecological unitsunits

LimitationsLimitations Ecological fallacyEcological fallacy Secondary data Secondary data

sourcessources ConfoundingConfounding Temporal Temporal

associationassociation Migration across Migration across

groupsgroups

Characteristics of Study Characteristics of Study DesignsDesigns

Unit of observati

on

E assesse

d before outcom

e?

Investigator controls

E?

RCT Individual

Yes Yes

Group RCT

Group Yes Yes

Cohort Individual

Yes No

Case-control

Individual

No No

X-sectional

Individual

No No

Ecological

“Group” No No

•Exposure(s) of interest?•Outcome(s) of interest?•Population investigated?•Recruitment?•Study design?•Strengths?•Limitations?