Overview of Study Designs

Study Designs Experimental Randomized Controlled Trial Group Randomized Trial Observational Descriptive Analytical Cross-sectional Ecological Cohort Case-control

Experimental v. Observational “Gold Standard” “Gold Standard” Investigator controls exposure Investigator controls exposure Less common Less common Investigator observes exposures Investigator observes exposures Most common Most common

4 INTERVENTION GROUP OUTCOME ASSESSMENT Present Future TIME Experimental Study: Randomized Controlled Trial Randomly Assigns Intervention Comparison

Randomized Controlled Trial Randomization is random distribution or allocation of subjects into groups Randomization is random distribution or allocation of subjects into groups Treatment or intervention group Treatment or intervention group Comparison group (placebo, another tx, no tx, usual care) Comparison group (placebo, another tx, no tx, usual care) Helps ensure that both groups are similar re: known and unknown factors Helps ensure that both groups are similar re: known and unknown factors Two types of RCTs Two types of RCTs Preventive trials Preventive trials Therapeutic trials Therapeutic trials

Group Randomized Trial Unit of assignment = group Unit of assignment = group Unit of analysis = individual (usually) Unit of analysis = individual (usually) Investigator controls exposure status Investigator controls exposure status Randomly assigns group to intervention group Randomly assigns group to intervention group Exposure assessed before outcome Exposure assessed before outcome

7 Experimental Study Strengths Strengths Able to demonstrate causal association Able to demonstrate causal association Randomization deals with known and unknown confounders Randomization deals with known and unknown confounders Investigators directly control intervention Investigators directly control intervention Limitations Ethical concerns (equipoise) Gen practice ≠ artificial Expensive Power often an issue

Observational Studies Most common, by necessity Most common, by necessity Observes nature without intervention Observes nature without intervention Takes advantage of people’s natural exposures (choice, occupation, environment, residence) Takes advantage of people’s natural exposures (choice, occupation, environment, residence) Collect data and statistically analyze results Collect data and statistically analyze results Goal is to “mimic” experimental study Goal is to “mimic” experimental study Statistics more important and usually more complex Statistics more important and usually more complex Can be descriptive or analytic Can be descriptive or analytic

Study Designs Experimental Randomized Controlled Trial Group Randomized Trial Observational Descriptive Analytical Cross-sectional Ecological Cohort Case-control

Cohort Studies Two ways to assemble cohort: Two ways to assemble cohort: Group of individuals with common characteristic or experience (then assess exposure before outcome) Group of individuals with common characteristic or experience (then assess exposure before outcome) Select subjects without outcome according to exposure status (esp important for rare exposure) Select subjects without outcome according to exposure status (esp important for rare exposure) Followed over time to determine incidence of symptoms, disease, or death Followed over time to determine incidence of symptoms, disease, or death Analysis focuses on risk of outcome in exposed compared to unexposed groups Analysis focuses on risk of outcome in exposed compared to unexposed groups Unexposed is referent or comparison group Unexposed is referent or comparison group

Prospective Cohort Studies Only include outcome-free individuals Only include outcome-free individuals At risk of developing outcome At risk of developing outcome Followed into future to observe outcomes Followed into future to observe outcomes Can take long time to complete Can take long time to complete Important to re-assess exposures over time Important to re-assess exposures over time Useful design for rare exposures Useful design for rare exposures Not for rare outcomes Not for rare outcomes Advantage: exposure assessed before subject knows outcome status; temporal sequence Advantage: exposure assessed before subject knows outcome status; temporal sequence

12 EXPOSURE ASSESSMENT OUTCOME ASSESSMENT Present Future TIME Prospective Cohort Study Exposed Unexposed

Retrospective Cohort Studies Both exposure and outcome occur before study Both exposure and outcome occur before study Studies only prior outcomes Studies only prior outcomes Historical cohort reconstructed from existing data sources before study begins Historical cohort reconstructed from existing data sources before study begins Example: Effects of pesticide exposure on cancer mortality (cohort of factory workers employed by manufacturer identified from personnel records) Example: Effects of pesticide exposure on cancer mortality (cohort of factory workers employed by manufacturer identified from personnel records) Need good records with info on many variables Need good records with info on many variables Sometimes good outcome info not available Sometimes good outcome info not available

14 EXPOSURE ASSESSMENT OUTCOME ASSESSMENT Past Present TIME Retrospective Cohort Study Exposed Unexposed

15 Cohort Study Strengths Strengths Easier to differentiate cause from effect Easier to differentiate cause from effect Direct estimation of incidence Direct estimation of incidence Able to examine multiple outcomes Able to examine multiple outcomes Efficient for rare exposures Efficient for rare exposures Prospective Prospective Reduces recall bias Reduces recall bias Limitations Large sample size Prospective Long-term follow-up Expensive

Case-Control Studies Both exposure and outcome have occurred Both exposure and outcome have occurred Classified according to outcome status before exposure ascertained Classified according to outcome status before exposure ascertained Cases with outcome selected from well-defined source population Cases with outcome selected from well-defined source population Controls without outcome* sampled from population that produced cases Controls without outcome* sampled from population that produced cases Analysis focuses on odds of exposure in cases compared to controls Analysis focuses on odds of exposure in cases compared to controls

Case-Control Study Grouped on basis of past or current outcome Grouped on basis of past or current outcome Outcome already occurred before exposure assessed Outcome already occurred before exposure assessed May lead to biased recall May lead to biased recall May be difficult to establish temporality May be difficult to establish temporality Useful design for rare outcomes Useful design for rare outcomes Not for rare exposures Not for rare exposures Advantages: Advantages: Less expensive than cohort (usually) Less expensive than cohort (usually) Can look at multiple exposures Can look at multiple exposures

18 EXPOSURE ASSESSMENT OUTCOME ASSESSMENT PastPresent TIME Case-Control Study Cases (with outcome) Controls (without outcome)*

19 Case-Control Study Strengths Strengths Efficient for rare outcomes Efficient for rare outcomes Able to examine multiple exposures Able to examine multiple exposures Limitations ↑ possibility of bias Temporal association Inefficient for rare exposures

Cross-Sectional Studies Study population not selected based on outcome or exposure status Study population not selected based on outcome or exposure status Outcome and exposure assessed at same time Outcome and exposure assessed at same time Snapshot at single point in time Snapshot at single point in time Problems inferring temporal sequence Problems inferring temporal sequence Identify prevalent cases of long duration Identify prevalent cases of long duration

21 EXPOSURE ASSESSMENT OUTCOME ASSESSMENT PastPresent TIME Analytical Cross-Sectional Study Exposed Unexposed

22 Cross-Sectional Study Strengths Strengths Less time and resources Less time and resources No follow-up time involved No follow-up time involved More representative of well-defined general population More representative of well-defined general population Useful when onset is difficult to establish (incidence) Useful when onset is difficult to establish (incidence) Limitations Temporal association Potential for prevalence- incidence bias Not for rare exposures or outcomes Reverse causality

23 EXPOSURE ASSESSMENT OUTCOME ASSESSMENT PastPresent TIME Analytical Ecological Study Exposed Unexposed Note: Often in ecological studies, the exposures and outcomes are continuous measures

24 Ecological Study Strengths Strengths Relatively quick and inexpensive Relatively quick and inexpensive May be only appropriate design for research question May be only appropriate design for research question May be useful when intra- group variability in exposure is small May be useful when intra- group variability in exposure is small May provide greater inter- group variability across larger ecological units May provide greater inter- group variability across larger ecological units Limitations Ecological fallacy Secondary data sources Confounding Temporal association Migration across groups

Characteristics of Study Designs Unit of observation E assessed before outcome? Investigator controls E? RCTIndividualYes Group RCTGroupYes CohortIndividualYesNo Case- control IndividualNo X-sectionalIndividualNo Ecological“Group”No Exposure(s) of interest? Outcome(s) of interest? Population investigated? Recruitment? Study design? Strengths? Limitations?