Observational Studies

Investigator does not assign exposures. A descriptive study provides a description of exposures and outcomes, whereas an analytic study provides a measure of the association between exposure and outcome. Observational studies are hypothesis generating and cannot establish causal association. 

Case-control study: compares subjects with disease (cases) to those without disease (controls) for risk factors. It is useful for establishing hypotheses about aetiology, especially when a disease is rare. It cannot estimate the prevalence of disease. Controls and cases should be sufficiently similar in prognostic factors other than the risks of interest.  

• Nested case-control study: defines a cohort with suspected risk factors and a control is assigned for each case from within the cohort. Cases and controls are matched on calendar time and length of follow-up. 
• Case-cohort study: cases are not matched on calendar time or length of follow-up to controls. 

Cohort study:

• Prospective follows and assesses outcomes in exposed and unexposed groups over time. 
• Retrospective identifies populations with and without the exposure based on past records and assesses outcomes at the time of study. 

Before and after (pre-post) observational study: outcomes are measured before and after an exposure, that is not assigned by the investigator. Study participants in the pre- and post-periods may be the same or different. 

• Controlled before and after: the before-after effect of implementation in the intervention group is compared with a control group that has no intervention.

Cross-sectional (prevalence) study: evaluates the prevalence of exposures and outcomes at the same time. Temporal association is difficult to establish. 

Experimental

Investigator assigns exposures (treatments). 

Clinical trial: subjects with disease are placed in different treatment groups. The study population must be sufficiently similar and representative of the general population of patients. The intervention is compared to a placebo, no treatment or an alternative treatment. 

• Parallel randomised trial: subjects are unpredictably (randomly) allocated to intervention and control groups. This minimises the selection bias and confounding. 
• Parallel non-randomised trial: controls are selected using some predictable pattern, e.g., certain days of the week.  
• Historically controlled trial: controls are adopted from the past, e.g., medical records, or previous studies. 
• Cross-over trial: two groups undergo the same treatments at different time periods, i.e., each group serves as a control while the other group is undergoing intervention. The effect of the treatments needs to be reversible. 
• Factorial trial: different treatments are tested at the same time in the same population. The treatment effects should be independent. 

Community trial: groups of subjects are assigned to different treatments. 

Field trial: subjects without disease are placed in different preventative intervention groups.   

Bias 

References

• Essentials of Clinical Research Design (Pediatr Invest 2019)
• Classification of Observational Studies (Lancet 2002)
• NICE Glossary of Study Designs